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Sample records for azathioprine

  1. Azathioprine

    Science.gov (United States)

    ... is used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune ... you are taking azathioprine to prevent kidney transplant rejection, your doctor may start you on a high ...

  2. Azathioprine treatment during lactation

    DEFF Research Database (Denmark)

    Christensen, L.A.; Dahlerup, J.F.; Nielsen, M.J.

    2008-01-01

    BACKGROUND: Thiopurines are widely used to maintain remission in inflammatory bowel disease. Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants...... to 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk. METHODS: Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly...... for the following 5 h. RESULTS: The variation in the bioavailability of the drug was reflected in a wide range of peak plasma values of 6-mercaptopurine within the first 3 h. A similar curve, but with an hour's delay and at significantly lower concentrations varying from 2-50 microg/L, was seen in maternal milk...

  3. Compound list: azathioprine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available azathioprine AZP 00046 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/azathioprine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/azathioprine...vo/Liver/Single/azathioprine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc....jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/azathioprine.Rat.in_vivo.Liver.Repeat.zip ...

  4. Severe cholestatic hepatitis caused by azathioprine.

    Science.gov (United States)

    Eisenbach, Christoph; Goeggelmann, Christoph; Flechtenmacher, Christa; Stremmel, Wolfgang; Encke, Jens

    2005-01-01

    A male patient receiving azathioprine treatment for discoid lupus erythematodes developed severe cholestatic hepatitis between 14 and 21 days after initiation of the treatment with peak bilirubin levels of 62.4 mg/dL. Other causes of hepatic dysfunction including viral hepatitis were clinically and serologically excluded. Liver biopsy revealed cholestatic hepatocellular damage. At 14 days after discontinuation of azathioprine the liver function (transaminases and bilirubin) began to improve. Only alcaline phosphatase and gamma-glutamyl transferase remained elevated even after 4 months. This case argues for an idiosyncratic cholestatic hepatocellular damage caused by azathioprine.

  5. Azathioprine Hypersensitivity Syndrome: Two Cases of Febrile Neutrophilic Dermatosis Induced by Azathioprine

    Directory of Open Access Journals (Sweden)

    Majed Aleissa

    2017-01-01

    Full Text Available Background: Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine. Case 1: A 36-year-old male with ulcerative colitis presented with erythematous plaques, pustules and erosions on the lower back, buttocks and thighs associated with high fever (39°C 2 weeks after the initiation of azathioprine 100 mg/day. Additional findings included leukocytosis (18.6 g/L with neutrophilia (11.1 g/L and elevated C-reactive protein (128 mg/L. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. We increased the dose of prednisone to 1 mg/kg/day (60 mg/day and azathioprine was discontinued. He had marked improvement within 3 weeks and did not have any relapse with a 1-year follow-up. Case 2: A 57-year-old male with ulcerative colitis presented with erythematous plaques and pustules on the lower limbs associated with high fever (40°C 1 week after the initiation of azathioprine 75 mg/day. Leukocytosis with neutrophilia (13.6 g/L and elevated C-reactive protein (344 mg/L were among the laboratory findings. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. The dose of prednisone was increased to 20 mg/day and azathioprine was discontinued, which led to complete remission within 7 days. He did not have any relapse with a 6-month follow-up. Conclusion: The development of acute neutrophilic dermatitis 2 weeks after the initiation of azathioprine and the complete resolution after its withdrawal were in favor of azathioprine hypersensitivity syndrome. It should not be confused with Sweet syndrome associated with inflammatory bowel disease, as maintenance of azathioprine treatment may lead to life-threatening reactions.

  6. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter

    2010-01-01

    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  7. IMPDH1 promoter mutations in a patient exhibiting azathioprine resistance.

    Science.gov (United States)

    Roberts, R L; Gearry, R B; Barclay, M L; Kennedy, M A

    2007-10-01

    Around 9% of inflammatory bowel disease (IBD) patients are resistant to azathioprine. We hypothesized that these patients may carry mutations within inosine-5'-monophosphate dehydrogenase (IMPDH). To test this hypothesis, we screened 20 azathioprine-resistant patients for variations in the two IMPDH genes (IMPDH1 and IMPDH2) using dHPLC and DNA sequencing. A 9 bp insertion within the IMPDH1 P3 promoter was found in a patient exhibiting severe azathioprine resistance. The insertion is predicted to abolish a cAMP-response element (CRE) and was found to significantly reduce IMPDH1 P3 promoter activity in a luciferase reporter gene assay (P-value resistance observed in this patient. The absence of functional variants within the other patients indicates that if IMPDH genetic variability contributes to azathioprine resistance it does so infrequently.

  8. Early pregnancy azathioprine use and pregnancy outcomes.

    LENUS (Irish Health Repository)

    Cleary, Brian J

    2012-02-01

    BACKGROUND: Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular\\/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular\\/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness.

  9. Azathioprine in inflammatory bowel disease, a safe alternative?

    Directory of Open Access Journals (Sweden)

    A. A. Tanis

    1998-01-01

    Full Text Available Azathioprine and its metabolite 6-mercaptopurine are effective in the treatment of inflammatory bowel disease. They are mostly used for reduction of the use of steroids, maintenance therapy after remission induction by cyclosporin and treatment of fistulae in Crohn's disease. Adverse effects occur in about 15% of patients. The main side effects are pancreatitis, allergic reactions, fever and bone marrow suppression. Symptoms, management and prevention are discussed. A blood monitoring schedule is suggested. Azathioprine and 6-mercaptopurine seem to be safe in pregnancy. There may be a slight increased risk for developing a non-Hodgkin's lymphoma.

  10. An audit of thiopurine methyltransferase genotyping and phenotyping before intended azathioprine treatment for dermatological conditions

    DEFF Research Database (Denmark)

    Vestergaard, T; Bygum, A

    2009-01-01

    Summary Background. Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression. Aim. To evaluate the course of azathioprine treatment in people with TPMT heterozygosity and whether this d...

  11. Alternative modes of cyclophosphamide and azathioprine therapy in lupus nephritis

    NARCIS (Netherlands)

    Dinant, H. J.; Decker, J. L.; Klippel, J. H.; Balow, J. E.; Plotz, P. H.; Steinberg, A. D.

    1982-01-01

    Forty-one patients with systemic lupus erythematosus and glomerulonephritis were studied in a randomized drug trial. Thirteen patients received prednisone only (Group 1), 16 received oral cyclophosphamide and oral azathioprine (1 mg/kg body weight . d of each initially) (Group 2), and 12 were given

  12. Azathioprine use during pregnancy: Unexpected intrauterine exposure to metabolites

    NARCIS (Netherlands)

    de Boer, Nanne K. H.; Jarbandhan, Soeresh V. A.; de Graaf, Peer; Mulder, Chris J. J.; van Elburg, Ruurd M.; van Bodegraven, Adriaan A.

    2006-01-01

    INTRODUCTION: The use of azathioprine (AZA) in the treatment of autoimmune diseases during pregnancy are believed to be relatively safe, particularly taking into account the potential risks for mother and fetus should the underlying disease become active due to withdrawal of this thiopurine.

  13. Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine

    DEFF Research Database (Denmark)

    Pedersen, E G; Pottegård, A; Hallas, J

    2014-01-01

    The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine i...... increases the risk of NMSC in organ recipients and probably also in patients with other autoimmune disorders. No previous study has specifically investigated the risk of NMSC in myasthenia patients treated with azathioprine.......The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine...

  14. Testicular lymphocytic vasculitis treated with prednisolone and azathioprine.

    Science.gov (United States)

    Kanzawa, Yohei; Imai, Yukihiro; Mizuno, Yasushi; Nishioka, Hiroaki

    2017-07-01

    Testicular vasculitis is a rare condition and little is known about its morphological features. Herein, we report a case of testicular lymphocytic vasculitis, which is rarely documented, in an elderly man. He presented with left testicular swelling and fever, but without any signs of other organ involvement. He was effectively treated with prednisolone and azathioprine. This case report offers information related to the disease course and the importance of biopsy.

  15. The effect of azathioprine on anastomotic healing: an experimental study in rats

    DEFF Research Database (Denmark)

    Stolzenburg, Tilo; Ljungmann, Ken; Christensen, Henrik

    2007-01-01

    PURPOSE: The cytotoxic and immunosuppressive effects of azathioprine, which mitigate the disease activity in inflammatory bowel disease, may compromise the healing of intestinal anastomoses leading to an increased risk of anastomotic leakage. The effect of azathioprine treatment on intestinal...... healing was tested. METHODS: In an experimental study, rats were randomly given one oral dose of azathioprine (5 mg or 20 mg/kg body weight per day) or placebo. After 28 days of treatment, a left colonic anastomosis was performed. After three days of healing, the breaking strengths of the anastomoses were...... azathioprine doses has no inhibitory effect on colonic healing in rats. Udgivelsesdato: 2007-Dec...

  16. Nonmelanoma skin cancer risk awareness in azathioprine-treated myasthenia gravis patients.

    LENUS (Irish Health Repository)

    McGurgan, Iain J

    2015-10-01

    Increased rates of NMSC (nonmelanoma skin cancer) have recently been reported in people with MG (myasthenia gravis) receiving azathioprine treatment. Guidelines on azathioprine for patients with dermatological and gastrointestinal disorders stress the importance of NMSC risk awareness and prevention. The aim of this study is to assess whether MG patients are being informed of this risk.

  17. Azathioprine-induced shock in a patient suffering from undifferentiated erosive oligoarthritis

    NARCIS (Netherlands)

    Demirtaş-Ertan, G.; Rowshani, A. T.; ten Berge, I. J. M.

    2006-01-01

    Shock due to a hypersensitivity response to azathioprine is unpredictable, occurs seldom and bears a potentially fatal outcome. Azathioprine is widely used in the treatment of autoimmune diseases and in solid organ transplantation. Here, we present a patient who suffered from undifferentiated

  18. Protective effect of pumpkin seed oil against genotoxicity induced by azathioprine

    Directory of Open Access Journals (Sweden)

    S.A. Elfiky

    2012-10-01

    Full Text Available Pumpkin is a leafy green vegetable; it belongs to the Cucurbitaceae family. Pumpkin seed oil supplementation can prevent changes in plasma lipids and blood pressure. The present study was conducted to evaluate the protective effect of pumpkin seed oil against cytotoxicity and genotoxicity of azathioprine. Oral administration of pumpkin seed oil either before or after treatment of azathioprine was effective in the reduction of the frequencies of Mn-PCEs, decreased the DNA fragmentation, total sperm abnormalities and significantly increased sperm count, percentage of PCEs, and enhanced the ratio of PCEs to NCEs. However, random amplified polymorphism of DNA (RAPD showed distinct differences in animal groups intoxicated with azathioprine before and after pumpkin seed oil treatment, which reflected a DNA protective effect of pumpkin seed oil. Depletion of glutathione content in the testis was also observed in azathioprine treated mice, which was improved by an oral administration of pumpkin seed oil either before or after treatment with azathioprine.

  19. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial

    NARCIS (Netherlands)

    Grootscholten, C.; Ligtenberg, G.; Hagen, E. C.; van den Wall Bake, A. W. L.; de Glas-Vos, J. W.; Bijl, M.; Assmann, K. J.; Bruijn, J. A.; van Houwelingen, H. C.; Derksen, R. H. W. M.; Berden, J. H. M.; Weening, J.J.

    Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001),

  20. Treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine

    NARCIS (Netherlands)

    de Glas-Vos, J. W.; Krediet, R. T.; Weening, J. J.; Arisz, L.

    1995-01-01

    OBJECTIVE: To evaluate the treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine. PATIENTS AND METHODS: Eighteen patients with severe proliferative lupus nephritis (Class III, IV or Vd according to criteria of the World Health Organization) were

  1. Azathioprine and mercaptopurine in the management of patients with chronic, active microscopic colitis

    DEFF Research Database (Denmark)

    Münch, A; Fernandez-Banares, F; Munck, L K

    2013-01-01

    BACKGROUND: Microscopic colitis (MC) is a common chronic diarrhoeal disease, and remission can be induced with budesonide. However, diarrhoea relapses frequently when budesonide is tapered and a few patients become budesonide intolerant. AIM: To examine retrospectively the effect of azathioprine ...

  2. Protective effect of pumpkin seed oil against genotoxicity induced by azathioprine

    OpenAIRE

    Elfiky, S.A.; Elelaimy, I.A.; Hassan, A.M.; Ibrahim, H.M.; Elsayad, R.I.

    2012-01-01

    Pumpkin is a leafy green vegetable; it belongs to the Cucurbitaceae family. Pumpkin seed oil supplementation can prevent changes in plasma lipids and blood pressure. The present study was conducted to evaluate the protective effect of pumpkin seed oil against cytotoxicity and genotoxicity of azathioprine. Oral administration of pumpkin seed oil either before or after treatment of azathioprine was effective in the reduction of the frequencies of Mn-PCEs, decreased the DNA fragmentation, total ...

  3. Use of azathioprine and the risk of cancer in inflammatory bowel disease.

    Science.gov (United States)

    Pasternak, Björn; Svanström, Henrik; Schmiegelow, Kjeld; Jess, Tine; Hviid, Anders

    2013-06-01

    Increased risks of lymphoma and skin cancer associated with thiopurine use among patients with inflammatory bowel disease have been shown, but data on the overall cancer risk are limited. We conducted a historical cohort study of 45,986 patients with inflammatory bowel disease (of whom, 5,197 (11%) used azathioprine) in Denmark from 1997 to 2008. We linked registry data on filled drug prescriptions, cancer diagnoses, and covariates and compared rates of overall incident cancer and cancer subgroups between users and nonusers of azathioprine, adjusting for propensity scores. During a median 7.9 (interquartile range: 3.5-12.0) person-years of follow-up, 2,596 incident cases of cancer were detected. Azathioprine use was associated with an increased risk of overall cancer (rate ratio = 1.41, 95% confidence interval: 1.15, 1.74), whereas former use of azathioprine (rate ratio = 1.02, 95% confidence interval: 0.83, 1.25) or increasing cumulative received doses (increase in rate ratio per 365 additional defined daily doses = 1.06, 95% confidence interval: 0.89, 1.27) were not. In subgroup analyses, azathioprine use was associated with increased risk of lymphoid tissue cancer (rate ratio = 2.40, 95% confidence interval: 1.13, 5.11) and urinary tract cancer (rate ratio = 2.84, 95% confidence interval: 1.24, 6.51). In conclusion, azathioprine use was associated with an increased risk of overall cancer in patients with inflammatory bowel disease, although these data cannot establish causality.

  4. Use of azathioprine for non-thymoma myasthenia and risk of cancer

    DEFF Research Database (Denmark)

    Pedersen, E G; Pottegård, Anton; Hallas, J

    2013-01-01

    BACKGROUND AND PURPOSE: To evaluate the association between the use of azathioprine and risk of cancer in patients with non-thymoma myasthenia gravis (MG) in a nationwide setting. METHODS: Case-control study based on population-based registries. Cases were patients with MG with a first time......; however, these risk estimates were based on small numbers. CONCLUSIONS: Use of azathioprine in patients with non-thymoma MG may be associated with a slightly increased risk of cancer overall. Larger studies are necessary to address the risk of site-specific cancers....

  5. Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression

    NARCIS (Netherlands)

    Zelinkova, Zuzana; Derijks, Luc J. J.; Stokkers, Pieter C. F.; Vogels, Esther W. M.; van Kampen, Antoine H. C.; Curvers, Wouter L.; Cohn, Danny; van Deventer, Sander J. H.; Hommes, Daniël W.

    2006-01-01

    BACKGROUND & AIMS: The use of azathioprine (AZA) in inflammatory bowel disease (IBD) patients is limited by toxicity, which occurs in up to 20% of treated patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genes have been associated with

  6. Azathioprine during pregnancy in systemic lupus erythematosus patients is not associated with poor fetal outcome.

    Science.gov (United States)

    Saavedra, Miguel Ángel; Sánchez, Antonio; Morales, Sara; Ángeles, Ulises; Jara, Luis Javier

    2015-07-01

    The objective of this study was to evaluate the risk of adverse fetal outcome in systemic lupus erythematosus (SLE) women exposed to azathioprine during pregnancy. We reviewed the medical records of SLE pregnant women followed from January 2005 to April 2013. The patients were evaluated at least once in each trimester and postpartum. Relevant fetal outcomes were extracted, such as rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. A detailed history of drug use during pregnancy was obtained. We studied 178 pregnancies (in 172 women), 87 of them were exposed to azathioprine (AZA-group) and the remaining 91 were not exposed (NO AZA-group). Exposure to other drugs was similar in both groups. The rate of live births, spontaneous abortions mean birth weight, weeks of gestation, rate of birth weight lupus flare, and anti-DNA positive were associated with an increased risk of poor fetal outcome. Our study suggests that the use of azathioprine is safe and lacks of teratogenity in patients with SLE and pregnancy. Exposure to azathioprine during pregnancy is not associated with poor fetal outcome.

  7. Evaluation of the effects of ascorbic acid on azathioprine-induced ...

    African Journals Online (AJOL)

    The use of azathioprine (AZA) in the prevention of organ rejection during transplantation has been noted in different organs of the body. This study investigates the effect of ascorbic acid on azathioprineinduced alteration in the testes of adult Wistar rats. Thirty male adult Wistar rats were randomly assigned into 5 groups ...

  8. Epstein-Barr-virus-associeret lymfom hos en patient med colitis ulcerosa i behandling med azathioprin

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Kiszka-Kanowitz, Marianne; Albrectsen, Jens Mørch

    2008-01-01

    A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV...

  9. Are pancreatic autoantibodies associated with azathioprine-induced pancreatitis in Crohn's disease?

    NARCIS (Netherlands)

    Weersma, Rinse K; Batstra, Manou R; Kleibeuker, Jan H; van Dullemen, Hendrik M

    2008-01-01

    CONTEXT: Azathioprine is frequently used in the treatment of Crohn's disease. A severe side effect is acute pancreatitis, which is specific for Crohn's disease. Autoantibodies against exocrine pancreas occur in about 30% of Crohn's disease cases but not in other inflammatory diseases. Pancreatic

  10. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

    Science.gov (United States)

    Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

    2014-01-01

    For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of

  11. Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.

    Science.gov (United States)

    Guenova, Emmanuella; Lichte, Verena; Hoetzenecker, Wolfram; Woelbing, Florian; Moehrle, Matthias; Roecken, Martin; Schaller, Martin

    2009-08-01

    Immunosuppressed patients are at increased risk of skin cancer. A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone. The patient died of metastatic disease 3 months after the diagnosis was made. The function of the renal graft was not affected at all. Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A. Less common is the development of skin cancer during immunosuppression with azathioprine. Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients. Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease.

  12. Addition of Azathioprine to Corticosteroids Does Not Benefit Patients with IgA Nephropathy

    Science.gov (United States)

    Andrulli, Simeone; Pani, Antonello; Scaini, Patrizia; Del Vecchio, Lucia; Fogazzi, Giambattista; Vogt, Bruno; De Cristofaro, Vincenzo; Allegri, Landino; Cirami, Lino; Procaccini, Aldo Deni; Locatelli, Francesco

    2010-01-01

    The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events. PMID:20634300

  13. Use of azathioprine and the risk of cancer in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Pasternak, Björn; Svanström, Henrik; Schmiegelow, Kjeld

    2013-01-01

    interval: 0.83, 1.25) or increasing cumulative received doses (increase in rate ratio per 365 additional defined daily doses = 1.06, 95% confidence interval: 0.89, 1.27) were not. In subgroup analyses, azathioprine use was associated with increased risk of lymphoid tissue cancer (rate ratio = 2.40, 95......Increased risks of lymphoma and skin cancer associated with thiopurine use among patients with inflammatory bowel disease have been shown, but data on the overall cancer risk are limited. We conducted a historical cohort study of 45,986 patients with inflammatory bowel disease (of whom, 5,197 (11.......9 (interquartile range: 3.5-12.0) person-years of follow-up, 2,596 incident cases of cancer were detected. Azathioprine use was associated with an increased risk of overall cancer (rate ratio = 1.41, 95% confidence interval: 1.15, 1.74), whereas former use of azathioprine (rate ratio = 1.02, 95% confidence...

  14. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder

    DEFF Research Database (Denmark)

    Nikoo, Zahra; Badihian, Shervin; Shaygannejad, Vahid

    2017-01-01

    Neuromyelitis optica spectrum disorder (NMOSD) often follows a relapsing course. As disability in NMOSD is attack-related, effective treatments are needed. We aimed to compare the efficacy of azathioprine (AZA) and rituximab (RIT) as maintenance therapy in NMOSD patients. An open, randomized...... clinical trial was conducted during September 2015 to December 2016, in Isfahan, Iran. Initially, 100 NMOSD patients were approached, 86 entered the study, and 68 cases completed the trial. All patients had a relapsing–remitting course with expanded disability extended scale (EDSS) ≤7 (median 2.75, range...

  15. Azathioprine therapy in a case of pediatric multiple sclerosis that was seropositive for MOG-IgG.

    Science.gov (United States)

    Zhou, Yifan; Huang, Qiao; Lu, Tingting; Sun, Xiaobo; Fang, Ling; Lu, Zhengqi; Hu, Xueqiang; Kermode, Allan; Qiu, Wei

    2017-04-01

    There is a lack of evidence for treatment of pediatric multiple sclerosis (PedMS). Treatment using azathioprine for PedMS has not been reported. A 10-year-old boy with multiple sclerosis who was seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG)-IgG was treated with azathioprine plus oral methylprednisolone. The patient showed clinical and magnetic resonance imaging stability, with MOG-IgG seroconversion. There were no major side effects over a 5-year period. Azathioprine may be a treatment option, particularly in poor medical resource areas, for pediatric patients with multiple sclerosis who are seropositive for MOG-IgG. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Endoscopic Recurrence 6 Months After Ileocecal Resection in Children With Crohn Disease Treated With Azathioprine.

    Science.gov (United States)

    Zarubova, Kristyna; Hradsky, Ondrej; Copova, Ivana; Rouskova, Blanka; Pos, Lucie; Skaba, Richard; Bronsky, Jiri

    2017-08-01

    Intestinal surgery is an important part of Crohn disease (CD) treatment in children. The aim of the present study was to compare the rate of endoscopic recurrence at the sixth month after ileocecal resection (ICR) in children with CD treated with azathioprine between patients who received prior antitumor necrosis factor alpha (anti-TNF-α) therapy and those who were not administered this therapy. Moreover, we tried to identify the potential risk factors for disease recurrence and describe the schedule of long-term follow-up after surgery. We prospectively collected data from pediatric patients with CD, who underwent ICR between October 2011 and June 2015 at our hospital and were treated with azathioprine monotherapy after ICR. We evaluated the endoscopic recurrence (Rutgeerts score) at the sixth month after ICR in all included patients. Among 21 included patients, 13 achieved endoscopic remission (Rutgeerts score factors associated with endoscopic recurrence rate at the sixth month. Prior anti-TNF-α therapy does not seem to be a strong risk factor for endoscopic recurrence within 6 months after ICR. Further studies on large sample of patients are needed to identify potential predictors of disease recurrence.

  17. Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Walsh, M.; Faurschou, M.; Berden, A.

    2014-01-01

    BACKGROUND AND OBJECTIVES: Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine...... after 3-6 months or after 12 months of cyclophosphamide treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time...

  18. More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing

    NARCIS (Netherlands)

    Broekman, Mark M.T.J.; Coenen, Marieke J H; van Marrewijk, Corine J; Wanten, Geert J A; Wong, Dennis R; Verbeek, Andre L.M.; Klungel, Olaf H.; Hooymans, Piet M; Guchelaar, Henk-Jan; Scheffer, Hans; Derijks, Luc J J; De Jong, Dirk J.

    2017-01-01

    Background: There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients

  19. Lack of evidence of a beneficial effect of azathioprine immune-mediated hemolytic anemia: a retrospective cohort study

    NARCIS (Netherlands)

    Piek, C.J.; Spil, Van W.E.; Junius, G.; Dekker, A.

    2011-01-01

    Background Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA

  20. Thiopurine Methyltransferase Enzyme Activity Determination before Treatment of Inflammatory Bowel Disease with Azathioprine: Effect on Cost and Adverse Events

    Directory of Open Access Journals (Sweden)

    Farzana A Sayani

    2005-01-01

    Full Text Available BACKGROUND: Azathioprine (AZA, used to treat inflammatory bowel disease (IBD, is metabolized by thiopurine methyltransferase (TPMT. The accumulation of individual metabolites varies because humans display genetic polymorphism for TPMT expression. Deficiencies in TPMT result in accumulation of toxic metabolites, followed by neutropenia and hepatic inflammation. Concern over acute toxicity frequently leads to under dosing and frequent monitoring tests and visits.

  1. Paradoxical elevated thiopurine S-methyltransferase activity after pancytopenia during azathioprine therapy: potential influence of red blood cell age

    NARCIS (Netherlands)

    de Boer, Nanne K. H.; van Bodegraven, Adriaan A.; de Graaf, Peer; van der Hulst, Rene W. M.; Zoetekouw, Lida; van Kuilenburg, André B. P.

    2008-01-01

    There is an increased risk of developing bone marrow depression and infections during azathioprine therapy for inflammatory bowel disease. Patients with low or absent thiopurine S-methyltransferase (TPMT) activity have an increased risk of developing myelotoxicity. We describe a patient who

  2. Svær interstitiel lungesygdom på grund af infliximab og azathioprin hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Hansen, L. K.; Cecere, Stefano; Thøgersen, Thøger

    2014-01-01

    A 41-year-old man developed severe interstitial lung disease (ILD) after treatment with infliximab (IFX) and azathioprine (AZA). A relapse of ulcerative colitis was treated with corticosteroids (CS) and IFX as rescue therapy. Following remission AZA was given as prophylaxis. AZA was initiated...

  3. Evaluation of the effectiveness of treatment with prednisone and azathioprine of autoimmune hepatitis in children.

    Science.gov (United States)

    Pniewska, Anna; Sobolewska-Pilarczyk, Małgorzata; Pawłowska, Małgorzata

    2016-01-01

    Autoimmune hepatitis is rarely diagnosed in children, but the course of the disease is often aggresive. Combination therapy with prednisone and azathioprine improves the prognosis of patients. To evaluate the effectiveness of combination therapy with prednisone and azathioprine of autoimmune hepatitis (AIH) in children. There was a retrospective analysis of the medical records of 15 patients with AIH, diagnosed before18 years of age, treated in the Provincial Infectious Diseases Hospital in Bydgoszcz in the years 2002 to 2013. We analysed the results of laboratory tests, ultrasound examination, endoscopy, and morphological liver pictures, as well as periods of exacerbation of inflammation and side effects of therapy. Biochemical remission of the disease was achieved on average after 36 days of treatment. Histopathological regression in the control liver biopsy was found in 7/15 patients and progression in 2/15 patients. In the study group 10/15 patients experienced exacerbation of the disease from 1 to 3 times during observation, with an increase of ALT activity to greater than 3 norm, and the remaining 5/15 patients had no increase of ALT activity. In total, 10 patients in the study group experienced 17 exacerbations. In 13/17 cases of exacerbations they were associated with a reduction in the dose of immunosuppressive drugs. There was no correlation between the biochemical exacerbation and changes in the histopathological image. Steroidside effects occurred in 14/15 patients. The treatment allows for biochemical remission of the disease and significantly improves the prognosis of most patients. However, significant side effects of treatment indicate the need for further exploration of effective and safe therapy, especially in the paediatric population.

  4. Treatment with cyclophosphamide delays the progression of chronic lesions more effectively than does treatment with azathioprine plus methylprednisolone in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Grootscholten, Cecile; Bajema, Ingeborg M.; Florquin, Sandrine; Steenbergen, Eric J.; Peutz-Kootstra, Carine J.; Goldschmeding, Roel; Bijl, Marc; Hagen, E. Christiaan; van Houwelingen, Hans C.; Derksen, Ronald H. W. M.; Berden, Jo H. M.

    2007-01-01

    OBJECTIVE: To analyze the effect of treatment with either pulse cyclophosphamide (CYC) or azathioprine (AZA) combined with methylprednisolone (MP), on serial biopsy results in patients with proliferative lupus nephritis, and to evaluate the predictive value of various histopathologic and clinical

  5. Treatment with cyclophosphamide delays the progression of chronic lesions more effectively than does treatment with azathioprine plus methylprednisolone in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Grootscholten, Cecile; Bajema, Ingeborg M.; Florquin, Sandrine; Steenbergen, Eric J.; Peutz-Kootstra, Carine J.; Goldschmeding, Roel; Bijl, Marc; Hagen, E. Christiaan; van Houwelingen, Hans C.; Derksen, Ronald H. W. M.; Berden, Jo H. M.

    Objective. To analyze the effect of treatment with either pulse cyclophosphamide (CYC) or azathioprine (AZA) combined with methylprednisolone (NIP), on serial biopsy results in patients with proliferative lupus nephritis, and to evaluate the predictive value of various histopathologic and clinical

  6. Rituximab for pulmonary lymphomatoid granulomatosis which developed as a complication of methotrexate and azathioprine therapy for rheumatoid arthritis

    OpenAIRE

    Barakat, Athar; Grover, Karan; Peshin, Rohit

    2014-01-01

    We report the case of a patient with Rheumatoid Arthritis [RA] presenting with clinical-pathological and radiological features of Pulmonary Lymphomatoid Granulomatosis (PLG). This is a rare lung disorder characterized by multiple nodular lesions with lymphocytic invasion of vascular walls. We present one such case of PLG secondary to Methotrexate and Azathioprine therapy, who was successfully treated with Steroids and Rituximab. We wish to highlight the importance of lung biopsy in the diagno...

  7. Successful low-dose azathioprine for myasthenia gravis despite hepatopathy from primary sclerosing cholangitis: a case report

    Directory of Open Access Journals (Sweden)

    Höflich Sonja

    2010-11-01

    Full Text Available Abstract Introduction Although myasthenia gravis is frequently associated with other disorders, it has not been reported together with primary sclerosing cholangitis, complicating the administration of liver-toxic immunosuppressive therapy. Case presentation A 73-year-old Caucasian woman with a history of arterial hypertension, thyroid dysfunction, glaucoma, right-sided ptosis and later generalized weakness, was diagnosed with myasthenia gravis. Additionally, primary sclerosing cholangitis was detected, initially prohibiting the administration of immunosuppressants. Despite treatment with steroids and pyridostigmine she repeatedly experienced myasthenic crises. After the fifth crisis and after antibody titers had reached levels > 100 nmol/L during two years of follow-up, it was decided to restart azathioprine. Interestingly, low-dose azathioprine (1.5 mg/kg/day was well tolerated, had a positive clinical and immunological effect and did not worsen primary sclerosing cholangitis. Conclusion Myasthenia gravis may occur together with primary sclerosing cholangitis in the same patient. Mild immunosuppression with azathioprine is feasible and effective in such a patient, without worsening myasthenia gravis or primary sclerosing cholangitis.

  8. Successful low-dose azathioprine for myasthenia gravis despite hepatopathy from primary sclerosing cholangitis: a case report

    Science.gov (United States)

    2010-01-01

    Introduction Although myasthenia gravis is frequently associated with other disorders, it has not been reported together with primary sclerosing cholangitis, complicating the administration of liver-toxic immunosuppressive therapy. Case presentation A 73-year-old Caucasian woman with a history of arterial hypertension, thyroid dysfunction, glaucoma, right-sided ptosis and later generalized weakness, was diagnosed with myasthenia gravis. Additionally, primary sclerosing cholangitis was detected, initially prohibiting the administration of immunosuppressants. Despite treatment with steroids and pyridostigmine she repeatedly experienced myasthenic crises. After the fifth crisis and after antibody titers had reached levels > 100 nmol/L during two years of follow-up, it was decided to restart azathioprine. Interestingly, low-dose azathioprine (1.5 mg/kg/day) was well tolerated, had a positive clinical and immunological effect and did not worsen primary sclerosing cholangitis. Conclusion Myasthenia gravis may occur together with primary sclerosing cholangitis in the same patient. Mild immunosuppression with azathioprine is feasible and effective in such a patient, without worsening myasthenia gravis or primary sclerosing cholangitis. PMID:21059205

  9. Design, development and optimization of oral colon targeted drug delivery system of azathioprine using biodegradable polymers.

    Science.gov (United States)

    Nath, Bipul; Nath, L K

    2013-01-01

    The present study was aimed at designing a microflora triggered colon targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to specifically deliver azathioprine in the colonic region for the treatment of IBD with reduced systemic toxicity. The microflora degradation properties of Sterculia gum was investigated in rat caecal phosphate buffer medium. The polysaccharide tablet cores were coated to different film thicknesses with blends of Eudragit RLPO and chitosan and overcoated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid, SGF (pH 1.2), simulated intestinal fluid, SIF (pH 6.8) and simulated colonic fluid, SCF (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the Sterculia gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora activated environment. The degradation of chitosan was the rate-limiting factor for drug release in the colon. Drug release from the MCDDS was directly proportional to the concentration of the pore former (chitosan), but inversely related to the Eudragit RLPO coating thickness.

  10. Azathioprine induced Epstein-Barr virus positive mucocutaneous ulcer: A case report

    Directory of Open Access Journals (Sweden)

    Arneja S

    2018-02-01

    Full Text Available Introduction: Epstein-Barr virus positive mucocutaneous ulcer (EBVMUC is a rare, newly described provisional entity in the 2016 Update of World Health Organization classification of lymphoid neoplasms. The histomorphological and immunophenotypical and molecular features overlap with classical Hodgkin’s lymphoma (cHL and can be mistaken for the same. Case report: A 70-year-old male, a known case of diabetes mellitus and hypertension, was diagnosed with Wegener’s granulomatosis (granulomatosis with polyangiitis in 2007. He was treated with prednisolone and cyclophosphamide, the latter drug was replaced with azathioprine in 2010. He was apparently well since then, until he presented in 2016 with an anal ulcer with a fistula tract formation, the ulcer on histomorphology and immunohistochemistry was diagnosed as EBVMUC. Discussion: EBVMUC was first described in patients with iatrogenic induced immunosuppression.They have later been found to be associated with various other causes of immunosuppression, like solid organ transplant recipients and human immunodeficiency virus (HIV, common factor in all these being immunosuppression. Conclusion: The importance of recognizing this entity lies in its morphological and immunophenotypic overlap with classical Hodgkin’s lymphoma (cHL and unlike latter, most often complete resolution of disease occurs with reduction of immunosuppressive dose. Therefore, correct recognition of the entity is essential to avoid overtreatment as lymphoma.

  11. Leukopenia due to parvovirus B19 in a Crohn's disease patient using azathioprine.

    Science.gov (United States)

    van Asseldonk, Dirk P; Kanis, Bernardina M; de Boer, Nanne K H; van Bodegraven, Ad A

    2009-01-01

    Thiopurines such as azathioprine (AZA) and 6-mercaptopurine are frequently used for the treatment of inflammatory bowel diseases. Patients with low or absent thiopurine S-methyltransferase (TPMT) activity, resulting in high 6-thioguanine nucleotide levels, have an increased risk of developing leukopenia. Alternatively, certain viral infections could induce leukopenia. We present the case of an adult Crohn's disease patient with a parvovirus B19 infection and leukopenia during long-term AZA therapy. The uncomplicated long-term use of adequately-dosed AZA and stable non-toxic metabolite levels could not acknowledge TPMT deficiency as a primary cause of the leukopenia. parvovirus B19 was assumed to induce the leukopenia by restraining myeloid proliferation. In addition, AZA probably potentiated susceptibility to this viral infection and may have inhibited adequate immunological defense. Leukopenia during thiopurine therapy not explained by TPMT deficiency could be induced by parvovirus B19 infection and compels temporal but not permanent cessation of thiopurine therapy. Copyright 2009 S. Karger AG, Basel.

  12. TPMT genetic variants are associated with increased rejection with azathioprine use in heart transplantation.

    Science.gov (United States)

    Liang, Jackson J; Geske, Jennifer R; Boilson, Barry A; Frantz, Robert P; Edwards, Brooks S; Kushwaha, Sudhir S; Kremers, Walter K; Weinshilboum, Richard M; Pereira, Naveen L

    2013-12-01

    Azathioprine (AZA) is an important immunosuppressant drug used in heart transplantation (HTX). Consensus guidelines recommend that patients with thiopurine S-methyltransferase (TPMT) genetic variants be started on lower AZA dose because of higher active metabolite levels and risk of adverse events. However, in-vitro lymphocyte proliferation assays performed in participants with inactive TPMT alleles have suggested that AZA use may result in decreased immunosuppressant efficacy as compared with wild-type (WT) individuals. The objective of this study was therefore to determine the effect of TPMT genetic variation on AZA efficacy or prevention of rejection in HTX recipients treated with AZA. We genotyped 93 HTX recipients treated with AZA and measured erythrocyte TPMT enzyme activity. Acute rejection was monitored by routine endomyocardial biopsies. There were 83 WT and 10 heterozygote (HZ) HTX recipients. TPMT activity level was lower in HZ compared with WT (13.1±2.8 vs. 21±4.5 U/ml red blood cell, Prejection earlier (Prejection score was higher (P=0.02) than WT. AZA was discontinued more frequently in HZ (P=0.01) because of rejection. The incidence of leukopenia was similar between the groups (40 vs. 43%, P=1.0). HTX recipients with TPMT genetic variant alleles who are treated with AZA develop acute rejection earlier, more frequently, and of greater severity. These patients, despite having lower TPMT enzymatic activity, should be monitored carefully for possible increased risk of acute rejection.

  13. [Role of Azathioprine in steroid resistant non infectious ocular inflammatory diseases].

    Science.gov (United States)

    Cuchacovich, Miguel; Pacheco, Patricio; Díaz, Gonzalo; Rojas, Basilio; Stoppel, Juan; Merino, Guillermo; Verdaguer, Juan Ignacio; Verdaguer, Juan; Villarroel, Francisco

    2007-06-01

    Topical and systemic steroids are the first line of treatment of non infectious inflammatory ocular disease. Immunosuppresants are reserved as a second line treatment. To evaluate the role of Azathioprine (AZA) as a coadyuvant immunosuppressive treatment for non infectious ocular inflammatory diseases (OIDs) resistant to systemic steroid therapy in a retrospective, noncomparative interventional case series. Patients using oral Prednisone due to an active or recurrent OID, without clinical response, and not receiving any other immunosuppressive treatment were studied. A standard protocol of oral Prednisone (0.5 mg/kg/ day) and oral AZA (2-3 mg/kg/day) during one year was used. Ocular and systemic monthly evaluations were done including relapse rate, steroid dosage, inflammatory score and visual acuity. Thirty patients (10 male) aged 18-75 years (mean 44 years) were studied. Three had bilateral anterior uveitis, one had pars planitis, four had diffuse uveitis, eight Vogt-Koyanahi-Harada syndrome, three Behget's disease, three necrotizing scleritis and eight had retinochoroidopathy A complete initial response was observed in 26 patients (87%). The time of response was between 1 to 6 months (mean 2.65 months). Seventeen percent of these had a relapse 6 to 12 months after AZA was started. In 61 %, visual acuity improved. The ocular inflammatory score decreased in 86.5%. Eleven patients had mild controlled side effects that did not require discontinuation of AZA. Combined systemic steroid and oral AZA therapy is safe and effective in controlling steroid resistant non infectious inflammatory ocular diseases.

  14. Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System

    Directory of Open Access Journals (Sweden)

    Abdullah Al Maruf

    2014-01-01

    Full Text Available Azathioprine (AZA is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using “Accelerated Cytotoxicity Mechanism Screening” techniques. The concentration of AZA required to cause 50% cytotoxicity in 2 hrs at 37°C was found to be 400 μM. A significant increase in AZA-induced cytotoxicity and reactive oxygen species (ROS formation was observed when glutathione- (GSH- depleted hepatocytes were used. The addition of N-acetylcysteine decreased cytotoxicity and ROS formation. Xanthine oxidase inhibition by allopurinol decreased AZA-induced cytotoxicity, ROS, and hydrogen peroxide (H2O2 formation and increased % mitochondrial membrane potential (MMP. Addition of N-acetylcysteine and allopurinol together caused nearly complete cytoprotection against AZA-induced hepatocyte death. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, a known ROS scavenger and a superoxide dismutase mimic, and antioxidants, like DPPD (N,N′-diphenyl-p-phenylenediamine, Trolox (a water soluble vitamin E analogue, and mesna (2-mercaptoethanesulfonate, also decreased hepatocyte death and ROS formation. Results from this study suggest that AZA-induced cytotoxicity in isolated rat hepatocytes may be partly due to ROS formation and GSH depletion that resulted in oxidative stress and mitochondrial injury.

  15. Recurrent Hepatocellular Carcinoma in Patient with Crohn’s Disease: Incidental or Expected Outcome of Azathioprine?

    Directory of Open Access Journals (Sweden)

    Youssef Botros

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC usually occurs in patients with underlying risk factors such as liver cirrhosis and chronic hepatitis B. Although patients with Crohn’s disease (CD are at an increased risk to develop malignancies such as colon cancer, the incidence of HCC in this population is extremely rare. We report a case of 62-year-old male with long history of CD treated with azathioprine (AZA and aminosalicylic acid (ASA who was incidentally diagnosed with HCC, for which left hepatectomy was done. Four years later during routine follow-up, patient had another hepatic lesion and underwent resection of the mass. The mechanism of occurrence of HCC in patient with CD is still controversial and may include immune mediated changes and medication related complications. AZA was reported in all case reports of CD that developed HCC. Through this report we hope to explore the complex pathophysiological mechanisms contributing to the development of HCC in the Crohn’s disease patient population.

  16. Late-onset Rise of 6-MMP Metabolites in IBD Patients on Azathioprine or Mercaptopurine.

    Science.gov (United States)

    Munnig-Schmidt, Erik; Zhang, Mei; Mulder, Chris J; Barclay, Murray L

    2018-03-19

    The thiopurines azathioprine and mercaptopurine remain pivotal maintenance treatments in inflammatory bowel disease (IBD); however, up to 15%-20% of patients preferentially produce the hepatotoxic metabolite 6-methylmercaptopurine (6MMP) at the expense of the therapeutic 6-thioguanine nucleotides (6TGN). This metabolic shunting usually begins within 3 months of therapy. We noted patients developing shunting many months or years after starting treatment and aimed to determine how often this late shunting occurs and whether this could be explained by patient factors or concomitant medications. The New Zealand database of thiopurine metabolite results from 2002 to 2016 (19085 6TGN/6MMP pairs from 7130 patients) was interrogated to identify patients developing a 6MMP/6TGN ratio >20 after at least 4 months treatment. Dosing history, concomitant therapy, and comorbidity data were assessed. Fifteen percent of database patients developed preferential 6-MMP production, and of these, 29 patients had late-onset shunting with sufficient data available for validation. This extrapolates to 90 patients in total, representing 1.7% of IBD patients on thiopurines, or 10% of all those with preferential 6-MMP production. Time from starting therapy to shunting was 5 months to 10.4 years (median, 21 months). Eleven patients had abnormal liver function when shunting was recognized, all with 6MMP >5900 pmol/8 × 108 red blood cells. No common factors were found to explain the late onset. Some IBD patients develop preferential 6MMP production many months or years after commencing therapy. This is important when considering frequency of metabolite monitoring, failure of therapy, or abnormal liver function. 10.1093/ibd/izx081_video1izx081.video15746667546001.

  17. Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior.

    Directory of Open Access Journals (Sweden)

    Natália Schneider

    Full Text Available Glucocorticoids and immunosuppressive drugs are commonly used to treat inflammatory disorders, such as inflammatory bowel disease (IBD, and despite a few improvements, the remission of IBD is still difficult to maintain. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs have emerged as regulators of the immune response, and their viability and activation of their migratory properties are essential for successful cell therapy. However, little is known about the effects of immunosuppressant drugs used in IBD treatment on MSC behavior. The aim of this study was to evaluate MSC viability, nuclear morphometry, cell polarity, F-actin and focal adhesion kinase (FAK distribution, and cell migratory properties in the presence of the immunosuppressive drugs azathioprine (AZA and dexamethasone (DEX. After an initial characterization, MSCs were treated with DEX (10 μM or AZA (1 μM for 24 hrs or 7 days. Neither drug had an effect on cell viability or nuclear morphometry. However, AZA treatment induced a more elongated cell shape, while DEX was associated with a more rounded cell shape (P < 0.05 with a higher presence of ventral actin stress fibers (P < 0.05 and a decrease in protrusion stability. After 7 days of treatment, AZA improved the cell spatial trajectory (ST and increased the migration speed (24.35%, P < 0.05, n = 4, while DEX impaired ST and migration speed after 24 hrs and 7 days of treatment (-28.69% and -25.37%, respectively; P < 0.05, n = 4. In conclusion, our data suggest that these immunosuppressive drugs each affect MSC morphology and migratory capacity differently, possibly impacting the success of cell therapy.

  18. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal.

    Science.gov (United States)

    Cassinotti, Andrea; Actis, Giovanni C; Duca, Piergiorgio; Massari, Alessandro; Colombo, Elisabetta; Gai, Elisa; Annese, Vito; D'Albasio, Giuseppe; Manes, Gianpiero; Travis, Simon; Porro, Gabriele Bianchi; Ardizzone, Sandro

    2009-11-01

    Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC. In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables. After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005). Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.

  19. Rituximab for pulmonary lymphomatoid granulomatosis which developed as a complication of methotrexate and azathioprine therapy for rheumatoid arthritis.

    Science.gov (United States)

    Barakat, Athar; Grover, Karan; Peshin, Rohit

    2014-01-01

    We report the case of a patient with Rheumatoid Arthritis [RA] presenting with clinical-pathological and radiological features of Pulmonary Lymphomatoid Granulomatosis (PLG). This is a rare lung disorder characterized by multiple nodular lesions with lymphocytic invasion of vascular walls. We present one such case of PLG secondary to Methotrexate and Azathioprine therapy, who was successfully treated with Steroids and Rituximab. We wish to highlight the importance of lung biopsy in the diagnosis and the use of rituximab as a treatment modality for RA as well as PLG.

  20. Micophenolat Mofetil Versus Azathioprine: Effects on Renal Graft Function in Early Posttransplant Period

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    Farid Ljuca

    2009-05-01

    Full Text Available All conventional immunosuppressive tree drugs-protocols are based on Cyclosporine; consisting of low doses of Cyclosporine (CsA, Azathioprine (AZA or Mycophenolate Mofetil (MMF and Prednisolone, AZA has been used in clinical transplantation for more than 30 years and was the first immunosuppres-sive agent to achieve widespread use in organ transplantation. MMF was introduced in clinical practice in 1995 after several clinical trials proved that it was more efficient than AZA for prevention of acute rejection episodes. Our aim was to evaluate influence of AZA and MMF on renal graft function in early post-transplant stage. Study recruited 74 patients who underwent kidney transplantation in University Clinical Centre Tuzla. All patients received CsA and corticosteroid-based immunosuppression, as a part of triple immunosuppressive regiment, 40 patients received AZA and 34 MMF. In order to assess renal graft function, following parameters were evaluated: glomerular filtration rate GFR (ml/min creatinine clearance (CrCl (ml/min, 24 h urine output (ml/day, and from the serum potassium, sodium, urea and creatinine (mmol/dm3. Significantly higher average values of 24 hour urine output were recorded during first seven postoperative days in patients receiving MMF compared to those treated with AZA. Serum creatinine values showed statistically significant decrease, starting with the second postoperative day, in MMF vs. AZA group (168,7±70,5 vs. 119,9±42,6; p<0,0007. GFR was significantly higher in MMF compared to the AZA group of patients. On the first post-transplant day CrCl was higher in AZA group (24,3±10 vs. 17,5±7,3; p=0,01, next six days situation is reversed CrCl is significantly higher in the MMF group (43,7±15 vs. 53, 4±22, 8 p=0,006. MMF vs. AZA therapy was associated with protective effect against worsening of renal function in first seven post-transplant days.

  1. Use of azathioprine and corticosteroids during pregnancy and birth outcome in women diagnosed with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Plauborg, Anne Veie; Hansen, Anne Vinkel; Garne, Ester

    2016-01-01

    was computed for each of the pregnancy trimesters and the year before and after pregnancy. Outcomes of interest were stillbirth, perinatal mortality, low birth weight (LBW), preterm birth, and small for gestational age (SGA). Results: Number of prescriptions for azathioprine decreased just before and during...... pregnancy and increased after birth. Number of prescriptions for local and systemic corticosteroids decreased approximately 30% compared with before pregnancy and increased in the second trimester. There was an increased risk among mothers with IBD of LBW (adjusted odds ratio [adjOR]: CD: 2.25 [95......% confidence interval {CI}, 1.74–2.91], UC: 1.81 [95% CI, 1.42–2.30]), preterm birth (adjOR: CD: 2.54 [95% CI, 2.04–3.15], UC: 1.86 [95% CI, 1.52–2.27]), and SGA (adjOR: CD: 1.99 [95% CI, 1.26–3.15], UC: 1.80 [95% CI, 1.18–2.75]). Conclusion: Use of azathioprine and corticosteroids was often reduced...

  2. Health-related quality of life and treatment burden in patients with proliferative lupus nephritis treated with cyclophosphamide or azathioprine/methylprednisolone in a randomized controlled trial

    NARCIS (Netherlands)

    Grootscholten, Cecile; Snoek, Frank J.; Bijl, Marc; van Houwelingen, Hans C.; Derksen, Ronald H. W. M.; Berden, Jo H. M.

    Objective. To study prospectively the effect of treatment with cyclophosphamide pulses (CYC) or azathioprine with methylprednisolone (AZA), both for 24-month periods, on health-related quality of life (HRQOL) in patients with proliferative lupus nephritis (LN) in a randomized controlled trial. We

  3. A prospective study of anti-chromatin and anti-C1q autoantibodies in patients with proliferative lupus nephritis treated with cyclophosphamide pulses or azathioprine/methylprednisolone

    NARCIS (Netherlands)

    Grootscholten, Cecile; Dieker, Jurgen W. C.; McGrath, Fabian D.; Roos, Anja; Derksen, Ronald H. W. M.; van der Vlag, Jakob; Daha, Mohamed R.; Berden, Jo H. M.

    2007-01-01

    Objective: To study the prevalence and course of anti-chromatin (anti-nucleosome, anti-double-stranded (ds) DNA and anti-histone) and anti-C1q autoantibodies in patients with proliferative lupus nephritis (LN), treated in a randomised controlled trial with either cyclophosphamide or azathioprine

  4. Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single-masked cross-over pilot study

    DEFF Research Database (Denmark)

    Sørensen, P.S.; Wanscher, B; Szpirt, W

    1996-01-01

    We enrolled 11 patients with secondary progressive MS in a randomized single-masked cross-over study of plasma exchange (PE) in combination with azathioprine 2 mg/kg. PE was performed once a week for 4 weeks and thereafter every second week for 20 weeks (14 treatments). Eight patients completed...

  5. DEVELOPMENT OF AZATHIOPRINE-BASED TREATMENT REGIMEN FOR PATIENTS WITH STEROID RESISTANT PEMPHIGUS BASED ON ASSESSMENT OF MOLECULAR MECHANISMS AT THE POST-RECEPTOR LEVEL

    Directory of Open Access Journals (Sweden)

    O. Yu. Olisova

    2016-01-01

    Full Text Available Background: Autoimmune pemphigus is the most severe skin and mucous membranes disorders with production of IgG autoantibodies to desmogleins 1 and 3. Administration of systemic corticosteroids may help to abrogate active signs of pemphigus. However, some patients do not give an adequate response to systemic glucocorticosteroid monotherapy, as well as to their combination with immune suppressants and cytostatic agents. Aim: To develop an azathioprine-based treatment regimen for patients with autoimmune pemphigus resistant to steroids. Materials and methods: At the first step of development of a treatment regimen for patients with steroid-resistant pemphigus we analyzed retrospectively a clinical database on 23 patients who had been treated from 2000 to 2014 and whose treatment regimen included azathioprine, in addition to systemic glucocorticosteroids. At the second step, from 2013 to 2015, we assessed and treated with the azathioprine-based regimen 24 patients with autoimmune pemphigus, 14  of them being steroid resistant and 10, steroid sensitive (control group. To assess molecular mechanisms of steroid resistance at the post-receptor level (effect of prednisolone on incorporation of ³Н-uridine into lymphocyte mRNA, changes of intracellular levels of nuclear transcription factor NF-κB we used a  real-time polymerase chain reaction, radioisotope method and liquid scintillation radiometry. Results: At the first step, we developed an azathioprine-based treatment regimen for patients with steroid resistant autoimmune pemphigus. Initial dose of azathioprine was 150 mg daily. After achievement of response, the dose was decreased to 100 mg daily. When the dose of systemic glucocorticosteroids was decreased to 20  mg daily, the dose of azathioprine was decreased to 50 mg daily, thereafter steroid resistant patients were taking azathioprine at a dose of 50 mg daily from 3  months to 2.5  years. Investigation of molecular mechanisms

  6. Azathioprine desensitizes liver cancer cells to insulin-like growth factor 1 and causes apoptosis when it is combined with bafilomycin A1

    International Nuclear Information System (INIS)

    Hernández-Breijo, Borja; Monserrat, Jorge; Román, Irene D.; González-Rodríguez, Águeda; Fernández-Moreno, M. Dolores

    2013-01-01

    Hepatoblastoma is a primary liver cancer that affects children, due to the sensitivity of this tumor to insulin-like growth factor 1 (IGF-1). In this paper we show that azathioprine (AZA) is capable of inhibiting IGF1-mediated signaling cascade in HepG2 cells. The efficiency of AZA on inhibition of proliferation differs in the evaluated cell lines as follows: HepG2 (an experimental model of hepatoblastoma) > Hep3B (derived from a hepatocellular carcinoma) > HuH6 (derived from a hepatoblastoma) ≫ HuH7 (derived from a hepatocellular carcinoma) = Chang Liver cells (a non-malignant cellular model). The effect of AZA in HepG2 cells has been proven to derive from activation of Ras/ERK/TSC2, leading to activation of mTOR/p70S6K in a sustained manner. p70S6K phosphorylates IRS-1 in serine 307 which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of PI3K) and therefore causing the lack of response of HepG2 to IGF-1. As a consequence, proliferation induced by IGF-1 is inhibited by AZA and autophagy increases leading to senescence of HepG2 cells. Our results suggest that AZA induces the autophagic process in HepG2 activating senescence, and driving to deceleration of cell cycle but not to apoptosis. However, when simultaneous to AZA treatment the autophagy was inhibited by bafilomycin A1 and the degradation of regulatory proteins of cell cycle (e.g. Rb, E2F, and cyclin D1) provoked apoptosis. In conclusion, AZA induces resistance in hepatoblastoma cells to IGF-1, which leads to autophagy activation, and causes apoptosis when it is combined with bafilomycin A1. We are presenting here a novel mechanism of action of azathioprine, which could be useful in treatment of IGF-1 dependent tumors, especially in its combination with other drugs. - Highlights: • Azathioprine activated Ras/ERK/TSC-2/mTOR/p70S6K signaling pathway in HepG2 cells. • Azathioprine inhibited IGF-1-mediated signaling cascade. • Azathioprine induced autophagy leading to cell cycle

  7. Azathioprine desensitizes liver cancer cells to insulin-like growth factor 1 and causes apoptosis when it is combined with bafilomycin A1

    Energy Technology Data Exchange (ETDEWEB)

    Hernández-Breijo, Borja [Departamento de Biología de Sistemas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); Monserrat, Jorge [Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, 28871 Alcalá de Henares (Spain); Román, Irene D. [Departamento de Biología de Sistemas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); González-Rodríguez, Águeda [Departamento de Biomedicina y Biotecnología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); Fernández-Moreno, M. Dolores [Departamento de Biología de Sistemas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); and others

    2013-11-01

    Hepatoblastoma is a primary liver cancer that affects children, due to the sensitivity of this tumor to insulin-like growth factor 1 (IGF-1). In this paper we show that azathioprine (AZA) is capable of inhibiting IGF1-mediated signaling cascade in HepG2 cells. The efficiency of AZA on inhibition of proliferation differs in the evaluated cell lines as follows: HepG2 (an experimental model of hepatoblastoma) > Hep3B (derived from a hepatocellular carcinoma) > HuH6 (derived from a hepatoblastoma) ≫ HuH7 (derived from a hepatocellular carcinoma) = Chang Liver cells (a non-malignant cellular model). The effect of AZA in HepG2 cells has been proven to derive from activation of Ras/ERK/TSC2, leading to activation of mTOR/p70S6K in a sustained manner. p70S6K phosphorylates IRS-1 in serine 307 which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of PI3K) and therefore causing the lack of response of HepG2 to IGF-1. As a consequence, proliferation induced by IGF-1 is inhibited by AZA and autophagy increases leading to senescence of HepG2 cells. Our results suggest that AZA induces the autophagic process in HepG2 activating senescence, and driving to deceleration of cell cycle but not to apoptosis. However, when simultaneous to AZA treatment the autophagy was inhibited by bafilomycin A1 and the degradation of regulatory proteins of cell cycle (e.g. Rb, E2F, and cyclin D1) provoked apoptosis. In conclusion, AZA induces resistance in hepatoblastoma cells to IGF-1, which leads to autophagy activation, and causes apoptosis when it is combined with bafilomycin A1. We are presenting here a novel mechanism of action of azathioprine, which could be useful in treatment of IGF-1 dependent tumors, especially in its combination with other drugs. - Highlights: • Azathioprine activated Ras/ERK/TSC-2/mTOR/p70S6K signaling pathway in HepG2 cells. • Azathioprine inhibited IGF-1-mediated signaling cascade. • Azathioprine induced autophagy leading to cell cycle

  8. Erythrocyte mean corpuscular volume as a surrogate marker for 6-thioguanine nucleotide concentration monitoring in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine.

    Science.gov (United States)

    Thomas, Carlton W; Lowry, Philip W; Franklin, Curtis L; Weaver, Amy L; Myhre, Gennett M; Mays, Dennis C; Tremaine, William J; Lipsky, James J; Sandborn, William J

    2003-07-01

    Mean corpuscular volume may correlate with erythrocyte 6-thioguanine nucleotide concentrations in patients treated with azathioprine and 6-mercaptourine. We conducted a study of 166 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentrations, disease activity as measured by the Inflammatory Bowel Disease Questionnaire (active disease 170), and leukopenia. Blood was submitted for mean corpuscular volume, whole blood 6-thioguanine nucleotide concentration, and leukocyte count. The mean +/- SD mean corpuscular volume during treatment was 94.7 +/- 6.6 fL and the mean +/- SD change in mean corpuscular volume was 7.5 +/- 6.3 fL. There were significant correlations between mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentration (r(s) = 0.33, p < 0.001) and between change from baseline in mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentration (r(s) = 0.26, p = 0.001). There was no correlation between Inflammatory Bowel Disease Questionnaire scores and mean corpuscular volume values (r(s) = 0.01, p = 0.94). The mean corpuscular volume values in 55 patients with active disease and 111 patients in remission were similar (95.1 vs. 94.5 fL, p = 0.57). There was a weak negative correlation between the mean corpuscular volume and the leukocyte count, (r(s) = -0.18, p = 0.022). In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, mean corpuscular volume and change from baseline in mean corpuscular volume correlated with erythrocyte 6-thioguanine nucleotide concentrations and negatively with leukocyte counts, but did not correlate with disease activity as measured by the Inflammatory Bowel Disease Questionnaire. Measurement of mean corpuscular volume is a simple and inexpensive alternative to measurement of 6-thioguanine nucleotide concentrations in

  9. Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single-masked cross-over pilot study

    DEFF Research Database (Denmark)

    Sørensen, P.S.; Wanscher, B; Szpirt, W

    1996-01-01

    We enrolled 11 patients with secondary progressive MS in a randomized single-masked cross-over study of plasma exchange (PE) in combination with azathioprine 2 mg/kg. PE was performed once a week for 4 weeks and thereafter every second week for 20 weeks (14 treatments). Eight patients completed...... in the two periods. Although the total MS lesion load on MRI was significantly lower (p effect of PE or encourage a subsequent large...

  10. Metastatic Hepatocellular Carcinoma in a Patient with Crohn’s Disease Treated with Azathioprine and Infliximab: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Kyle J. Fortinsky

    2014-01-01

    Full Text Available Hepatocellular carcinoma most commonly occurs in patients with underlying liver disease or cirrhosis. We describe a case of hepatocellular carcinoma in a 34-year-old man with Crohn’s disease treated with azathioprine and infliximab. The patient had no history of liver disease and a complete autoimmune and viral workup was unremarkable. Unfortunately, the patient developed widespread metastatic disease and passed away 5 months after his initial diagnosis. The mechanism of hepatocellular carcinoma in patients’ with Crohn’s disease is poorly understood and may include both autoimmunity and treatment-related complications. Previous case reports suggest the possibility of a concerning association between azathioprine therapy and the development of hepatocellular carcinoma in patients with Crohn’s disease. Clinicians may consider early imaging in patients with Crohn’s disease presenting with concerning symptomatology or abnormal liver enzymes, especially in those being treated with azathioprine alone or in combination with infliximab. Future research may help to uncover additional risk factors for this exceedingly rare diagnosis in this patient population.

  11. Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

    Science.gov (United States)

    Mohl, Wolfgang; Bokemeyer, Bernd; Bündgens, Burkhard; Büning, Jürgen; Miehlke, Stephan; Hüppe, Dietrich; Maaser, Christian; Klugmann, Tobias; Kruis, Wolfgang; Siegmund, Britta; Helwig, Ulf; Weismüller, Joseph; Drabik, Attyla; Stallmach, Andreas

    2016-01-01

    Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor. PMID:26468141

  12. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    International Nuclear Information System (INIS)

    Henkenberens, Christoph; Christiansen, Hans; Franzke, Anke; Raab, Peter; Oschlies, Ilske; Klapper, Wolfram

    2014-01-01

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I E A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [de

  13. Human herpes virus-6 encephalitis causing severe anterograde amnesia associated with rituximab, azathioprine and prednisolone combination therapy for dermatomyositis.

    Science.gov (United States)

    Baumer, Thomas; Fry, Charlie; Luppe, Sebastian; Gunawardena, Harsha; Sieradzan, Kasia

    2017-06-01

    Human herpes virus-6 (HHV-6) reactivation is a well-recognised complication following haematological stem cell transplantation, but it is novel in the context of combination immunomodulatory therapy for autoimmune disease. We report a case of severe anterograde amnesia caused by HHV-6 encephalitis in a young female patient on rituximab, azathioprine and prednisolone for dermatomyositis (DM). The use of targeted biologic treatments for systemic autoimmune connective tissue diseases (CTDs) is increasing, particularly when refractory to conventional management. The anti-CD20 B cell depleting monoclonal antibody, rituximab is now increasingly used, often in combination with conventional immunomodulatory treatments, in certain autoimmune neurological conditions and systemic CTDs including DM. Physicians should be aware of the possibility of HHV-6 in those who develop encephalitis while CD20 B cell deplete, especially in the presence of additional immunomodulatory therapies. Prompt diagnosis and treatment of HHV-6 encephalitis with evidence-based anti-viral therapy may help reduce the extent of irreversible morbidity such as amnesia.

  14. Non-detectable levels of 6-thioguanine nucleotides and 6-methylmercaptopurine in a patient treated with azathioprine: a case report

    Science.gov (United States)

    Wong, D R; den Dulk, M O; Derijks, L J J; Gemmeke, E H K M; Hooymans, P M

    2007-01-01

    Introduction: Azathioprine (AZA) is a thiopurine prodrug clinically used for immunosuppression in the treatment of auto-immune inflammatory diseases and in regimens of organ transplantations. The pharmacological action of AZA is based on the formation of 6-mercaptopurine (6-MP), which is metabolised into a variety of active thiopurine-nucleotide metabolites. We report the case of a 55 year old woman (bodyweight 30 kg) with chronic pancreatitis, weight loss, and progressive elevation of liver transaminases and serum amylase. Case description: The woman was treated with prednisolone (30 mg 1 dd; tapered 5 mg each week) and AZA (75 mg 1 dd; 5 weeks later 150 mg 1 dd). Despite good patient-compliance verified during hospital-stay, none of the active metabolites of AZA, 6-thioguanine-nucleotides (6TGN) and 6-methylmercaptopurine ribonucleotides (6MMPR), were detected in erythrocytes. After two months of treatment clinical improvement was achieved, but no normalisation of laboratory parameters. Subsequently, AZA was switched to 6-MP 75 mg 1 dd, and allopurinol 100 mg 1 dd was added. After one week the 6TGN level was 616 pmol/ 8 × 108 red blood cells (RBC), the 6MMPR level was 1319 pmol/ 8 × 108 RBC. Two weeks later the 6TGN level was 1163 pmol/ 8 × 108 RBC and the 6MMPR level 10015 pmol/ 8 × 108 RBC. These 6TGN and 6MMPR levels were higher than the upper limits of the therapeutic ranges (500 pmol/ 8 × 108 RBC and 5700 pmol/ 8 × 108 RBC, respectively). Therefore, treatment with 6-MP was discontinued. A week later the 6TGN and 6MMPR levels decreased to 686 pmol/ 8 × 108 RBC and 4027 pmol/ 8 × 108 RBC, respectively. Genotyping of the enzym thiopurine S-methyl transferase (TPMT) revealed a wild-type TPMT (*1/*1) genotype. Discussion: To our knowledge this is the first report of a patient who was not able to form detectable active thiopurine metabolites on the treatment with AZA. AZA is normally rapidly and almost completely converted to 6-MP and methylnitroimidazole

  15. Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception

    DEFF Research Database (Denmark)

    Nørgård, B M; Magnussen, B; Larsen, M D

    2017-01-01

    OBJECTIVE: Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception...... and adverse birth outcomes. DESIGN: This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did...... not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624). The outcomes were congenital abnormalities (CAs), preterm birth and small for gestational age (SGA). We adjusted for multiple covariates and performed a restricted analysis of men with IBD. RESULTS: There were...

  16. Hemossiderose pulmonar idiopática tratada com azatioprina: relato de caso em criança Idiopathic pulmonary hemosiderosis treated with azathioprine in a child

    Directory of Open Access Journals (Sweden)

    Clemax Couto Sant`Anna

    2007-12-01

    Full Text Available A hemossiderose pulmonar idiopática (HPI, principal causa de hemossiderose pulmonar em crianças, cursa com sangramento alveolar intermitente e presença de hemossiderófagos no escarro ou no lavado gástrico. O tratamento é baseado nos corticoesteróides e citostáticos, em condições especiais. Descreve-se o caso de uma menina de sete anos com HPI, que conseguiu controle parcial da doença mediante altas doses de corticoesteróide. O tratamento, no entanto, necessitou ser suspenso gradualmente visto a paciente ter desenvolvido fácies cushingóide. Foi iniciada a associação da azatioprina ao corticóide até a substituição total por azatioprina isolada, cujo uso foi mantido por quatro anos, com ótimo resultado.Idiopathic pulmonary hemosiderosis (IPH, the main cause of pulmonary hemosiderosis in children, is characterized by intermittent alveolar bleeding and hemosiderin-laden macrophages in sputum and in gastric lavage. The treatment is based on corticosteroids and cytotoxic drugs, under special conditions. We describe the case of a 7-year-old girl with IPH who achieved partial clinical remission with high doses of corticosteroids. However, the treatment had to be discontinued because the patient developed Cushing's syndrome. Treatment was started with an azathioprine-corticosteroid combination and then changed to azathioprine alone, which was maintained for four years, with excellent results.

  17. New and cost effective cell-based assay for Dialyzed Leukocyte Extract (DLE)-induced Jurkat cells proliferation under azathioprine treatment.

    Science.gov (United States)

    Cardoso, F M; Tomkova, M; Petrovajova, D; Bubanova, M; Ragac, O; Hornakova, T

    2017-05-10

    The human Dialyzed Leukocyte Extract (DLE) is a heterogeneous mix of oligopeptides of cell-based assay. The A20 and Jurkat cell lines were treated with (+Aza) or without (-Aza) azathioprine, DLE (+DLE) or both (+Aza/+DLE). After 72h, the cell proliferation was analyzed by the MTT or BrdU incorporation assays. In +Aza/+DLE treated cells, we observed a significant higher proliferation, when compared with +Aza/-DLE. In the absence of Aza, cells did not present any proliferation difference between -DLE or +DLE treatments. Both assays, MTT and BrdU showed similar results, being the MTT test more cost effective and we select it for validation as DLE biological assay using Jurkat cells only. We tested three different lyophilized DLE batches and we found consistent results with acceptable assay reproducibility and linearity. The DLE capacity for rescuing Jurkat cell proliferation during +Aza treatment was consistent using different liquid and lyophilized DLE batches, presenting also consistent chromatographic profiles. Finally, DLE treatment in Jurkat cells did not result into significant IL-2 of IFN-γ secretion, and known lymphocyte proliferative drugs failed to rescue Jurkat cells viability in presence of +Aza, as +DLE treatment did in our MTT assay. In conclusion, our new cell-based MTT assay has excellent DLE biological activity consistency, robustness and is cost effective, presenting important advantages over previous DLE activity in vitro and in vivo assays. Copyright © 2017. Published by Elsevier B.V.

  18. Glassy carbon electrodes modified with a film of nanodiamond-graphite/chitosan: Application to the highly sensitive electrochemical determination of Azathioprine

    Energy Technology Data Exchange (ETDEWEB)

    Shahrokhian, Saeed, E-mail: shahrokhian@sharif.ed [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of); Institute for Nanoscience and Technology, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Ghalkhani, Masoumeh [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of)

    2010-04-15

    A novel modified glassy carbon electrode with a film of nanodiamond-graphite/chitosan is constructed and used for the sensitive voltammetric determination of azathioprine (Aza). The surface morphology and thickness of the film modifier are characterized using atomic force microscopy. The electrochemical response characteristics of the electrode toward Aza are investigated by means of cyclic voltammetry. The modified electrode showed an efficient catalytic role for the electrochemical reduction of Aza, leading to a remarkable decrease in reduction overpotential and enhancement of the kinetics of the electrode reaction with a significant increase of peak current. The effects of experimental variables, such as the deposited amount of modifier suspension, the pH of the supporting electrolyte, the accumulation potential and time were investigated. Under optimal conditions, the modified electrode showed a wide linear response to the concentration of Aza in the range of 0.2-100 muM with a detection limit of 65 nM. The prepared modified electrode showed several advantages: simple preparation method, high stability and uniformity in the composite film, high sensitivity, excellent catalytic activity in physiological conditions and good reproducibility. The modified electrode can be successfully applied to the accurate determination of trace amounts of Aza in pharmaceutical and clinical preparations.

  19. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Henkenberens, Christoph; Christiansen, Hans [Medizinische Hochschule Hannover, Klinik fuer Strahlentherapie und Spezielle Onkologie, Hannover (Germany); Franzke, Anke [Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation, Hannover (Germany); Raab, Peter [Medizinische Hochschule Hannover, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Hannover (Germany); Oschlies, Ilske; Klapper, Wolfram [Universitaetsklinikum Schleswig-Holstein, Institut fuer Pathologie, Sektion Haematopathologie, Kiel (Germany)

    2014-09-15

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I{sub E}A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [German] Retrospektive und prospektive Kohortenstudien deuten daraufhin, dass eine Beteiligung des zentralen Nervensystems (ZNS) in etwa bei 0,5 % der Patienten mit fortgeschrittenem Hodgkin-Lymphom auftritt. Die isoliert primaer intrakranielle Manifestation des Hodgkin-Lymphoms ist extrem selten, mit wenigen bisher bekannten Faellen. Wenig ist auch ueber die optimale

  20. A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.

    Science.gov (United States)

    Ellison, G W; Myers, L W; Mickey, M R; Graves, M C; Tourtellotte, W W; Syndulko, K; Holevoet-Howson, M I; Lerner, C D; Frane, M V; Pettler-Jennings, P

    1989-08-01

    Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.

  1. Exploring associations of 6-thioguanine nucleotide levels and other predictive factors with therapeutic response to azathioprine in pediatric patients with IBD using multilevel analysis.

    Science.gov (United States)

    Nguyen, Thi-Van-Anh; Vu, Dinh Hoa; Nguyen, Thi-Mai-Hoang; Lachaux, Alain; Boulieu, Roselyne

    2013-10-01

    Metabolite monitoring and response predictors to azathioprine (AZA) in pediatric inflammatory bowel disease (IBD) are debatable. In an attempt to optimize thiopurine therapy and understand the mechanism of action of thiopurines, we correlated metabolites and other factors with AZA efficacy in children with IBD. Data from 86 children with IBD with 440 metabolite measurements were retrospectively analyzed using multilevel logistic regression analyses. A therapeutic response was defined as a pediatric Crohn's disease activity index ≤10 for Crohn's disease or a pediatric ulcerative colitis activity index ≤10 for ulcerative colitis without any treatment with steroids, antitumor necrosis factor, other immunomodulators, or exclusive enteral nutrition. The 6-thioguanine nucleotide levels >250 pmol per 8 × 10 red blood cells correlated with a higher response (odds ratio, 4.14; 95% confidence interval, 1.49-11.46, P = 0.007), whereas 6-methyl-mercaptopurine and 6-methyl-mercaptopurine:6-thioguanine nucleotide ratio showed no correlation. Other novel response predictors in children with IBD were relative leukopenia (odds ratio, 14.01; 95% confidence interval, 3.77-52.10; P response. Age, gender, patient adherence, the duration of AZA therapy, IBD type, erythrocyte count, and erythrocyte sedimentation rate did not predict efficacy. The high interindividual variability accounting for 57.7% of variance in therapeutic response was observed. The significant 6-thioguanine nucleotide level-response relationship may support metabolite monitoring to improve thiopurine efficacy in pediatric IBD. The reported response predictors may be helpful for treatment optimization in AZA-treated children with IBD, but should be proved in prospective studies.

  2. Monitoração terapêutica da azatioprina: uma revisão Therapeutic drug monitoring of azathioprine: a review

    Directory of Open Access Journals (Sweden)

    Maurílio Pacheco Neto

    2008-06-01

    Full Text Available Os nucleotídeos de tioguanina (6-TGN, metabólitos ativos da azatioprina (AZA e da 6-mercaptopurina (6-MP, atuam como antagonistas das purinas, inibindo as sínteses de DNA, RNA e a protéica, e induzindo à citotoxicidade/imunossupressão. A enzima geneticamente determinada, tiopurina metiltransferase (TPMT, está envolvida no metabolismo desses agentes e, hipoteticamente, determina a resposta clínica às tiopurinas. A baixa atividade dessa enzima diminui a metilação das tiopurinas, resultando em potencial sobredose, enquanto altos níveis de TPMT levam à superprodução do metabólito tóxico 6-metilmercaptopurina (6-MMP e à não-efetividade terapêutica da AZA e da 6-MP. Várias mutações no gene da TPMT têm sido identificadas e correlacionadas com fenótipos de baixa atividade. Neste artigo, também se discute a monitoração terapêutica desses fármacos por meio da medida dos níveis de 6-TGN intra-eritrocitários, os quais se correlacionam com imunossupressão e mielotoxicidade. Já a 6-MMP está diretamente relacionada com hepatotoxicidade. Esses ensaios estão associados ao uso de doses adequadas dessa droga, resultando num melhor controle da doença e menor uso de corticosteróides.Thioguanine nucleotides (6-TGN, active metabolites of azathioprine (AZA and 6-mercaptopurine (6-MP, act as purine antagonists, inhibiting DNA, RNA, and protein synthesis and inducing cytotoxicity and immunosuppression. The genetically determined thiopurine methyltransferase enzyme (TPMT is involved in the metabolism of these agents and, theoretically, determines the clinical response to thiopurines. Low activity of this enzyme decreases the methylation of thiopurines, what results in potential overdosing, whereas high TPMT status leads to overproduction of toxic metabolite 6-methilmercaptopurine (6-MMP and ineffectiveness of AZA and 6-MP. Several mutations in the TPMT gene have been identified and correlated with low activity phenotypes. In this

  3. Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States

    Directory of Open Access Journals (Sweden)

    Lund JL

    2013-12-01

    Full Text Available Jennifer L Lund,1 Suzanne F Cook,2 Jeffery K Allen,2 Charlotte F Carroll,2 Michael D Kappelman3 1Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 2Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background and aims: Thiopurines, including 6-mercaptopurine (6-MP and azathioprine (AZA, are the mainstay of maintenance therapy for Crohn's disease (CD. However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. Methods: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001–2008 (n=3,657. We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan–Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the “noncontinuers,” we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. Results: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years and individuals with no prior anti-tumor necrosis factor (TNF use were more likely to continue 6-MP/AZA, while those dispensed more (>4 outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39% and 105 (4% individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. Conclusion: Most patients initiating 6-MP

  4. HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease.

    Science.gov (United States)

    Wilson, A; Jansen, L E; Rose, R V; Gregor, J C; Ponich, T; Chande, N; Khanna, R; Yan, B; Jairath, V; Khanna, N; Sey, M; Beaton, M; McIntosh, K; Teft, W A; Kim, R B

    2018-03-01

    Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2%-7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine-induced pancreatitis. To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles. A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype. The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02-36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80-145.26, P = 0.0001) for homozygous variant (C/C) patients. The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD. © 2017 John Wiley & Sons Ltd.

  5. Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial.

    Science.gov (United States)

    Puéchal, Xavier; Pagnoux, Christian; Baron, Gabriel; Quémeneur, Thomas; Néel, Antoine; Agard, Christian; Lifermann, François; Liozon, Eric; Ruivard, Marc; Godmer, Pascal; Limal, Nicolas; Mékinian, Arsène; Papo, Thomas; Ruppert, Anne-Marie; Bourgarit, Anne; Bienvenu, Boris; Geffray, Loïck; Saraux, Jean-Luc; Diot, Elisabeth; Crestani, Bruno; Delbrel, Xavier; Sailler, Laurent; Cohen, Pascal; Le Guern, Véronique; Terrier, Benjamin; Groh, Matthieu; Le Jeunne, Claire; Mouthon, Luc; Ravaud, Philippe; Guillevin, Loïc

    2017-11-01

    In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate. © 2017

  6. Defining the ultrasound longitudinal natural history of newly diagnosed pediatric small bowel Crohn disease treated with infliximab and infliximab-azathioprine combination therapy.

    Science.gov (United States)

    Dillman, Jonathan R; Dehkordy, Soudabeh Fazeli; Smith, Ethan A; DiPietro, Michael A; Sanchez, Ramon; DeMatos-Maillard, Vera; Adler, Jeremy; Zhang, Bin; Trout, Andrew T

    2017-07-01

    Little is known about changes in the imaging appearances of the bowel and mesentery over time in either pediatric or adult patients with newly diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha (anti-TNF-α) therapy. To define how bowel ultrasound findings change over time and correlate with laboratory inflammatory markers in children who have been newly diagnosed with pediatric small bowel Crohn disease and treated with infliximab. We included 28 pediatric patients treated with infliximab for newly diagnosed ileal Crohn disease who underwent bowel sonography prior to medical therapy and at approximately 2 weeks, 1 month, 3 months and 6 months after treatment initiation; these patients also had laboratory testing at baseline, 1 month and 6 months. We used linear mixed models to compare mean results between visits and evaluate whether ultrasound measurements changed over time. We used Spearman rank correlation to assess bivariate relationships. Mean subject age was 15.3±2.2 years; 11 subjects were girls (39%). We observed decreases in mean length of disease involvement (12.0±5.4 vs. 9.1±5.3 cm, P=0.02), maximum bowel wall thickness (5.6±1.8 vs. 4.7±1.7 mm, P=0.02), bowel wall color Doppler signal (1.7±0.9 vs. 1.2±0.8, P=0.002) and mesenteric color Doppler signal (1.1±0.9 vs. 0.6±0.6, P=0.005) at approximately 2 weeks following the initiation of infliximab compared to baseline. All laboratory inflammatory markers decreased at 1 month (P-valuesinfliximab, when adjusted for age, sex, azathioprine therapy, scanning radiologist and baseline short pediatric Crohn's disease activity index score. The ultrasound appearance of the bowel changes as early as 2 weeks after the initiation of infliximab therapy. There is strong correlation between bowel wall color Doppler signal and fecal calprotectin.

  7. NUDT15 p.R139C variant is common and strongly associated with azathioprine-induced early leukopenia and severe alopecia in Korean patients with various neurological diseases.

    Science.gov (United States)

    Kim, Sun-Young; Shin, Jin-Hong; Park, Jin-Sung; Kang, Sa-Yoon; Nam, Tai-Seung; Kim, Jong Kuk; Park, Ki-Jong; Huh, So-Young; Oh, Ji Seon; Kang, Boram; Kim, Dae-Seong

    2017-07-15

    Azathioprine (AZA)-induced leukopenia is a relatively common complication in Korean patients. In addition to variation in TPMT (thiopurine S-methyltransferase), the NUDT15 p.R139C variant was recently identified to have a strong association with AZA-induced leukopenia. We investigated these associations in Korean patients undergoing AZA treatment with various neurological diseases. Among 84 enrolled patients, 20 (23.8%; 7 early, 13 late) exhibited leukopenia. The NUDT15 p.R139C variant was associated with leukopenia (OR: 11.844, 95% CI 3.984-36.024, p=1.327 × 10 -5 ). The allelic frequency of NUDT15 p.R139C was as high as 10.7% and the frequency of the C/C, C/T, and T/T genotypes was 84.5, 10.7, and 5.9%, respectively. All T/T homozygous patients (5/5) developed early severe-grade leukopenia (white blood cells leukopenia and severe alopecia (OR for early leukopenia: 107.624, 95% CI 18.857-614.250, p=1.403 × 10 -7 , OR for severe alopecia: 77.152, 95% CI 17.378-342.526, p=1.101 × 10 -8 ). The sensitivity and specificity for predicting AZA-induced early leukopenia were 85.7% and 92.2%, respectively. Therefore, the NUDT15 p.R139C variant is common and strongly associated with AZA-induced early leukopenia and severe alopecia in Korean patients with various neurological diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Primary CNS lymphoma in a patient treated with azathioprine

    DEFF Research Database (Denmark)

    Glesner, Matilde Kanstrup; Ocias, Lukas Frans; Larsen, Thomas Stauffer

    2014-01-01

    with surrounding oedema. There was cerebrospinal fluid pleocytosis, and Epstein-Barr virus (EBV) DNA was detected in the spinal fluid by PCR. A brain biopsy confirmed the suspicion of primary brain lymphoma. EBV-associated primary brain lymphoma is a relevant differential diagnosis in patients with long......-standing immune suppression presenting with neurological symptoms. Detection of EBV DNA in the spinal fluid together with characteristic radiological findings may serve as a diagnostic clue for a quick diagnosis....

  9. Azathioprine and prednisone combination therapy in refractory coeliac disease.

    NARCIS (Netherlands)

    Goerres, MS; Meijer, JW; Wahab, PJ; Kerckhaert, JA; Groenen, PJ; Krieken, JH Van; Mulder, C.J.J.

    2003-01-01

    INTRODUCTION: Refractory coeliac disease (RCD) is a rare syndrome with a poor prognosis, defined by malabsorption due to gluten-related enteropathy after initial or subsequent failure of a strict gluten-free diet and after exclusion of any disorder mimicking coeliac disease. PATIENTS AND METHODS:

  10. Prescribing of sulfasalazine, azathioprine and methotrexate round pregnancy - a descriptive study

    NARCIS (Netherlands)

    Vroom, Fokaline; van Roon, Eric N.; van den Berg, Paul B.; Brouwers, Jacobus R. B. J.; den Berg, Lolkje T. W. de Jong-van

    Purpose Continuation or discontinuation of drugs during pregnancy in chronic diseases is an issue of concern. Information on prescribing of disease modifying anti-rheumatic drugs (DMARDs) during pregnancy is scarce. In this study, we report prescribing patterns round pregnancy of sulfasalazine

  11. Proteinuria following conversion from azathioprine to sirolimus in renal transplant recipients.

    NARCIS (Netherlands)

    Akker, J.M. van den; Wetzels, J.F.M.; Hoitsma, A.J.

    2006-01-01

    Recent studies have reported a significant increase of proteinuria in kidney transplant recipients who were switched from a calcineurin inhibitor (CI) to sirolimus. This has (partly) been ascribed to the hemodynamic renal effects of CI withdrawal. We have evaluated the evolution of proteinuria in

  12. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    International Nuclear Information System (INIS)

    Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J.

    1991-01-01

    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 x 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished

  13. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J. (Department of Veterinary Microbiology, Immunology and Parasitology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States))

    1991-06-01

    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 {times} 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished.

  14. Entérite lupique récidivante améliorée par Azathioprine | Marzouk ...

    African Journals Online (AJOL)

    L'entérite lupique constitue l'une des manifestations responsable de douleurs abdominales. Son traitement est basé essentiellement sur les corticoïdes. Le recours aux immunosuppresseurs est réservé aux formes récidivantes ou en cas d'échec des corticoïdes. Nous rapportons une nouvelle observation d'entérite lupique ...

  15. Long term azathioprine maintenance therapy in ANCA-associated vasculitis: combined results of long-term follow-up data.

    Science.gov (United States)

    de Joode, Anoek A E; Sanders, Jan Stephan F; Puéchal, Xavier; Guillevin, Loic P; Hiemstra, Thomas F; Flossmann, Oliver; Rasmussen, Nils; Westman, Kerstin; Jayne, David R; Stegeman, Coen A

    2017-11-01

    We studied whether in ANCA-associated vasculitis patients, duration of AZA maintenance influenced relapse rate during long-term follow-up. Three hundred and eighty newly diagnosed ANCA-associated vasculitis patients from six European multicentre studies treated with AZA maintenance were included; 58% were male, median age at diagnosis 59.4 years (interquartile range: 48.3-68.2 years); granulomatosis with polyangiitis, n = 236; microscopic polyangiitis, n = 132; or renal limited vasculitis, n = 12. Patients were grouped according to the duration of AZA maintenance after remission induction: ⩽18 months, ⩽24 months, ⩽36 months, ⩽48 months or > 48 months. Primary outcome was relapse-free survival at 60 months. During follow-up, 84 first relapses occurred during AZA-maintenance therapy (1 relapse per 117 patient months) and 71 after withdrawal of AZA (1 relapse/113 months). During the first 12 months after withdrawal, 20 relapses occurred (1 relapse/119 months) and 29 relapses >12 months after withdrawal (1 relapse/186 months). Relapse-free survival at 60 months was 65.3% for patients receiving AZA maintenance >18 months after diagnosis vs 55% for those who discontinued maintenance ⩽18 months (P = 0.11). Relapse-free survival was associated with induction therapy (i.v. vs oral) and ANCA specificity (PR3-ANCA vs MPO-ANCA/negative). Post hoc analysis of combined trial data suggest that stopping AZA maintenance therapy does not lead to a significant increase in relapse rate and AZA maintenance for more than 18 months after diagnosis does not significantly influence relapse-free survival. ANCA specificity has more effect on relapse-free survival than duration of maintenance therapy and should be used to tailor therapy individually. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  16. [Role of Rac1 signaling pathway of azathioprine and peptidoglycan in the regulation of monocyte-macrophage apoptosis in Crohn's disease].

    Science.gov (United States)

    Zhou, Z; Jing, Y; Ran, Y; Zhao, J; Zhou, L; Wang, B M

    2018-04-01

    Objective: To evaluate the changes of macrophages and expression of Rac1 in the inflammatory site of Crohn's disease, and to investigate the effects of 6-thioguanine (6-TG) and peptidoglycan on apoptosis of human peripheral blood monocyte-macrophage by regulating Rac1 signaling pathway. Methods: Ten patients with Crohn's disease and eight healthy controls diagnosed were enrolled at Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital from January 2013 to January 2014. The number of macrophages, apoptosis and expression of Rac1 in the inflammation sites and non-inflammation sites of intestinal mucosa were detected in both patients and controls. Peripheral blood mononuclear cells (PBMCs) were sorted by CD 14 immunomagnetic beads. The apoptosis of monocytes, expression of Rac1 and related apoptosis signaling molecules were detected in patients treated with peptidoglycan, 6-TG and Rac1 inhibitor NSC23766 and another 15 healthy donors. Results: The number of macrophages and apoptotic cells significantly increased in the inflammatory group of Crohn's disease patients compared with the non-inflammatory group. The expression of PAK1, downstream molecular of Rac1 signaling pathway of macrophages was also significantly higher in the inflammatory group of Crohn's disease patients than that in healthy controls and non-inflammatory group. Compared with control group, anti-apoptotic signals (NF-κB, Bcl-xL and STAT-3) in PBMCs increased in the peptidoglycan group, while slightly decreased in 6-TG group. 6-TG and NSC23766 significantly promoted peptidoglycan-related anti-apoptosis [peptidoglycan group (8.6±3.7)%, peptidoglycan+ 6-TG group (42.0±2.7)%, peptidoglycan+ NSC23766 group (58.5±6.9)%, PRac1 signaling pathway leading to macrophage apoptosis.

  17. Paternal use of azathioprine/6-mercaptopurine or methotrexate within 3 months before conception and long-term health outcomes in the offspring

    DEFF Research Database (Denmark)

    Friedman, S; Larsen, M D; Magnussen, B

    2017-01-01

    : children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524). OUTCOMES: malignancies, autism spectrum disorders (ASD)/schizophrenia/psychosis, and attention deficit...

  18. Thiopurines and inhibition of Rac1 in vascular disease

    NARCIS (Netherlands)

    Marinković, G.

    2015-01-01

    The mechanism of immunosuppressive drug azathioprine is not clear, while azathioprine has been used for 60 years in clinical practice in patients undergoing transplantation surgery or to combat autoimmune disease. Part of the function of azathioprine became evident in specific immune cells, namely T

  19. Partial splenic ablation in preparation for renal transplantation in children.

    Science.gov (United States)

    Guzzetta, P C; Stolar, C H; Potter, B M; Broadman, L; Ruley, E J

    1983-12-01

    Patients with end-stage renal disease who develop hypersplenism, patients with mild neutropenia, and those patients whose WBC fails to increase in response to cortisol administration will develop significant neutropenia following transplantation with routine doses of azathioprine. This "intolerance" of azathioprine mandates a reduction in the dose of azathioprine often resulting in allograft rejection. Splenectomy will prevent azathioprine-induced neutropenia, but the hazards of splenectomy in these immunosuppressed patients have led to attempts to salvage at least part of the spleen. Partial splenic ablation by embolization has been utilized in adults prior to transplantation to prevent azathioprine-induced neutropenia while preserving the spleen's protective mechanisms against infection. Eight children in our series of transplant candidates required a reduction of splenic function to prevent azathioprine induced neutropenia. One child had a functioning renal allograft but had recurrent neutropenia limiting the azathioprine dose. Partial splenic embolization was attempted in four children and was initially successful in two. Both patients later developed recurrent neutropenia and needed partial splenectomy. The two patients in whom partial splenic embolization was unsuccessful and five further patients in whom embolization was not attempted also underwent partial splenectomy. Approximately 75% to 80% of the spleen was resected. Six children have since undergone renal transplantation and one child had a transplant with chronic rejection at the time of partial splenectomy. Routine doses of azathioprine have been used in these children with no episodes of neutropenia or sepsis observed. We recommend partial splenectomy in those children requiring renal transplantation who are at risk for development of azathioprine induced neutropenia.

  20. César Augusto Restrepo Valencia, Consuelo Vélez Álvarez Abstract Objective. To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods. Patients with lupus nephritis class IV-G who despite receiving therapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results. Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months

    Directory of Open Access Journals (Sweden)

    César Augusto Restrepo Valencia

    2014-10-01

    Full Text Available Objective: To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods: Patients with lupus nephritis class IV-G who despite receiving the rapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results: Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months of followup, of which 4 (40% had partial

  1. CME 8876.indd

    African Journals Online (AJOL)

    Sedating antihistamines. Thereafter, maintenance as for chronic disease. Ultraviolet (UV) light. Non-steroidal systemic drugs: azathioprine, cyclosporin, methotrexate, mycophenolate. Refer to dermatologist/paediatrician/allergist as appropriate. Potent TCSs. Phototherapy (narrow-band UVB). Cyclosporin, methotrexate, oral ...

  2. Refractory massive pleural effusion in systemic lupus erythematosus treated with talc poudrage.

    OpenAIRE

    Kaine, J L

    1985-01-01

    The case of a 31-year-old black male is presented with recurrent pleural effusion secondary to active SLE. Treatment with corticosteroids, azathioprine, plaquenil, and tetracycline pleural sclerosis was unsuccessful. Disease control was finally achieved by pleural talc poudrage.

  3. Laser Induced Breakdown Spectroscopy (LIBS)

    Science.gov (United States)

    2010-03-31

    Omphalutus olearus Panaeolus Pluteus Page 35 PLANTS Abrus precatorius L. Aconitum napellus spp. Arum...Methamidophos Ascorbic acid (PIM 046) Ammonium perchlorate composite propellant. Paraquat Dichloride Azathioprine (PIM 053) Ammonium perchlorate

  4. Biological therapy in the management of recent-onset Crohn's disease

    NARCIS (Netherlands)

    Lowenberg, Mark; Peppelenbosch, Maikel; Hommes, Daniel

    2006-01-01

    Crohn's disease is a chronic inflammatory bowel disease that may involve any part of the gastrointestinal tract. Conventional therapy consists of corticosteroids, azathioprine or methotrexate, but the clinical management of Crohn's disease is significantly hampered by adverse effects. With the

  5. Biological therapy in the management of recent-onset Crohn's disease: why, when and how?

    NARCIS (Netherlands)

    Löwenberg, Mark; Peppelenbosch, Maikel; Hommes, Daniel

    2006-01-01

    Crohn's disease is a chronic inflammatory bowel disease that may involve any part of the gastrointestinal tract. Conventional therapy consists of corticosteroids, azathioprine or methotrexate, but the clinical management of Crohn's disease is significantly hampered by adverse effects. With the

  6. Disease: H00029 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ype 18 [GN:T40088] ... Azathioprine [DG:DG00743] Tobacco smoking and tobacco smoke K...islop TG, Maden C, Mandelson MT, Beckmann AM, Weiss NS. ... TITLE ... Cigarette smoking and the risk of anogen

  7. Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999

    DEFF Research Database (Denmark)

    Andersen, V; Sonne, J; Andersen, M

    2001-01-01

    valproate (two cases), clomipramine (one case) and azathioprine (one case). Definite relationship was stated for mesalazine (three cases), azathioprine (two cases) and simvastatin (one case) on the basis of re-challenge. A possible or probable causality was considered for a further 30 drugs including 5......-acetylsalicylic acid agents, angiotensin-converting enzyme inhibitors, estrogen preparations, didanosine, valproate, codeine, antiviral agents used in acquired immunodeficiency syndrome therapy, various lipid-reducing agents, interferon, paracetamol, griseofulvin, ticlopine, allopurinol, lithium and the MMR...

  8. Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

    OpenAIRE

    Gallagher, Martin P.; Kelly, Patrick J.; Jardine, Meg; Perkovic, Vlado; Cass, Alan; Craig, Jonathan C.; Eris, Josette; Webster, Angela C.

    2010-01-01

    Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non–skin cancer (including melanoma) and skin c...

  9. Use of Axathioprine for Nongranulomatous Ulcerative Jejunoileitis

    Directory of Open Access Journals (Sweden)

    Robert Enns

    1997-01-01

    Full Text Available Nongranulomatous ulcerative jejunoileitis (NGUJI is a rare, often fatal disorder that produces multiple nonmalignant small bowel ulcerations. A 55-year-old woman with presumed celiac disease presented with steroid-refractory diarrhea, weight loss and abdominal pain. A laparotomy was performed to exclude the possibility of a lymphomatous disorder, and multiple nonmalignant small bowel ulcerations were discovered. Despite a combination of treatment with total parenteral nutrition (TPN and prednisone 30 mg/day she continued to deteriorate. The addition of azathioprine to her treatment regimen resulted in marked clinical and biochemical improvement. Her enteroscopy normalized, and she was able to discontinue TPN and reduce her steroid requirements. Although azathioprine has been used occasionally to treat refractory sprue, there have been no reports of its use in NGUJI. In this case, azathioprine played a key role in the management of NGUJI and should be considered a treatment option for patients with this disorder.

  10. Drug-induced eosinophilic pneumonia in a patient with Crohn's disease: diagnosis and treatment using fraction of exhaled nitric oxide

    Directory of Open Access Journals (Sweden)

    Jina Yeo

    2017-10-01

    Full Text Available Oral 5-aminosalicylic acid agents (mesalazine and sulfasalazine and azathioprine are the mainstays of treatment for inflammatory bowel disease. Reports of pulmonary toxicity induced by oral 5-aminosalicylic acid agents or azathioprine in patients with inflammatory bowel disease are very rare; to date, only 38 cases have been reported worldwide. We, herein, report a case involving a 26-year-old man who was diagnosed with eosinophilic pneumonia after using mesalazine and azathioprine for the treatment of Crohn's disease and recovered after treatment. We also found that the fraction of exhaled nitric oxide level was elevated in this patient. After treatment, the fraction of exhaled nitric oxide level decreased and the symptoms improved. The present case shows that fraction of exhaled nitric oxide is related to the disease activity and treatment effectiveness of druginduced eosinophilic pneumonia.

  11. Treatment outcomes in a cohort of patients with mucosal-predominant pemphigus vulgaris.

    Science.gov (United States)

    Ojaimi, S; O'Connor, K; Lin, M W; Schifter, M; Fulcher, D A

    2015-03-01

    Pemphigus vulgaris (PV) is a rare autoimmune blistering condition. Treatment typically combines corticosteroids with another immunosuppressive agent, such as azathioprine, mycophenolate mofetil (MMF) or rituximab. This study aims to compare these second agents for their clinical efficacy and steroid-sparing effect. This was a single-centre, retrospective observational cohort study of 21 patients with oral PV over a 6-year period, 18 of whom were newly diagnosed. Of the latter, the first 13 were initially given azathioprine, progressing to MMF and then rituximab on treatment failure, while the next five patients started directly on MMF. Of the 13 newly diagnosed patients, 2/13 were intolerant of azathioprine, and only 1/11 was controlled, with a median time to treatment failure (MTTF) of 254 days. MMF was given to 17 patients, either de novo (5) or after azathioprine (12), and was significantly more effective, controlling activity in 4/17 patients, and for a significantly longer time (MTTF 395 days, P = 0.019). All 13 patients failing MMF received rituximab, seven required a second dose, and three, a third dose. All patients responded, with 11/13 able to cease steroids. Control was maintained for a similar time to MMF (MTTF 364 days, P = NS). Rituximab also had the best steroid-sparing effect followed by MMF, then azathioprine. Side-effects were common with azathioprine, while the other two agents were well tolerated. Rituximab was the most effective of the three immunosuppressives for PV, although repeat dosing was frequently required. These observations have significant implications for the choice of drugs for this condition. © 2014 Royal Australasian College of Physicians.

  12. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  13. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  14. The role and advances of immunomodulator therapy for inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Steenholdt, Casper

    2015-01-01

    Immune modulating drugs such as thiopurines (azathioprine and 6-mercaptopurine) and methotrexate has been a mainstay for treatment of inflammatory bowel disease (IBD) for decades. However, despite widely used in IBD, questions still remain concerning the most rational treatment regimens of these ...

  15. Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Ainsworth, Mark Andrew

    2013-01-01

    A 35-year-old man presents with an exacerbation of Crohn's ileocolitis. He received a diagnosis of Crohn's disease 8 years ago and has been treated on three previous occasions with prednisone. Because of a recurrent need for glucocorticoids, treatment with azathioprine (150 mg per day) was starte...

  16. Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs

    DEFF Research Database (Denmark)

    Olsen, N; Halberg, P; Halskov, O

    1988-01-01

    In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed...

  17. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  18. Non-IgE-mediated food allergies

    African Journals Online (AJOL)

    routine treatment for children with EoE:[6,10]. • leukotriene antagonists. • cromolyn sodium. • omalizumab. • anti-interleukin-5 antibodies (mepolizumab, reslizumab ). • azathioprine, 6-mercaptopurine and antitumour necrosis factor. Oesophageal dilation. Oesophageal strictures, which are a recognised complication of EoE,.

  19. Topical and systemic pharmacological treatment of atopic dermatitis

    African Journals Online (AJOL)

    Topical steroids may be used for 10 - 14 days when the dermatitis is active .... warning to TCI labels noting that the long- term safety of ... mycophenylate and azathioprine as second- line options.[14]. Systemic corticosteroids. Systemic corticosteroids are frequently used for short-term therapy of severe AD, but their use is ...

  20. Induction of immunological tolerance in the pig-to-baboon xenotransplantation model : studies aimed at achieving mixed hematopoietic chimerism and preventing associated thrombotic complications

    NARCIS (Netherlands)

    I.P.J. Alwayn (Ian)

    2001-01-01

    textabstractThe outcome of clinical organ transplantation has dramatically improved since the introduction of cyclosporine (CyA) in 1979 and of other, more recently introduced, immunosuppressive agents such as azathioprine, mycophenolate mofetil, tacrolimus and sirolimus. Furthermore, due to more

  1. Hypercalcemia due to Primary Hepatic Lymphoma

    Directory of Open Access Journals (Sweden)

    Andrew Hsu

    2016-01-01

    Full Text Available A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient’s hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia.

  2. HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants

    NARCIS (Netherlands)

    Heap, Graham A.; Weedon, Michael N.; Bewshea, Claire M.; Singh, Abhey; Chen, Mian; Satchwel, Jack B.; Vivian, Julian P.; So, Kenji; Dubois, Patrick C.; Andrews, Jane M.; Annese, Vito; Bampton, Peter; Barnardo, Martin; Bell, Sally; Cole, Andy; Connor, Susan J.; Creed, Tom; Cummings, Fraser R.; D'Amato, Mauro; Daneshmend, Tawfique K.; Fedorak, Richard N.; Florin, Timothy H.; Gaya, Daniel R.; Greig, Emma; Halfvarson, Jonas; Hart, Alisa; Irving, Peter M.; Jones, Gareth; Karban, Amir; Lawrance, Ian C.; Lee, James C.; Lees, Charlie; Lev-Tzion, Raffi; Lindsay, James; Mansfield, John; Mawdsley, Joel; Mazhar, Zia; Parkes, Miles; Parnell, Kirstie; Orchard, Timothy R.; Radford-Smith, Graham; Russell, Richard K.; Reffitt, David; Satsangi, Jack; Silverberg, Mark S.; Sturniolo, Giacomo C.; Tremelling, Mark; Tsianos, Epameinondas V.; van Heel, David A.; Walsh, Alissa; Watermeyer, Gill; Weersma, Rinse K.; Zeissig, Sebastian; Rossjohn, Jamie; Holden, Arthur L.; Ahmad, Tariq

    2014-01-01

    Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of

  3. South African Medical Journal - Vol 96, No 12 (2006)

    African Journals Online (AJOL)

    Risk of malignancy in myasthenia gravis patients exposed to azathioprine therapy for a median period of 3 years · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. A Rawoot, F Little, JM Heckmann, 1249-1251 ...

  4. Data-Driven Identification of Structural Alerts for Mitigating the Risk of Drug-Induced Human Liver Injuries

    Science.gov (United States)

    2015-02-11

    our profiling (using the web tool at https:// ochem.eu/alerts/home.do) of 826 U.S. Food and Drug Administration (FDA)-approved oral drugs retrieved...1 Fluorouracil 0 Cortisone 1 Delavirdine 1 Disulfiram 1 Nilotinib 0 Betamethasone 1 Glyburide 1 Azathioprine 1 Fluphenazine 0 Testosterone 1

  5. International Journal of Biological and Chemical Sciences - Vol 8 ...

    African Journals Online (AJOL)

    Evaluation of the effects of ascorbic acid on azathioprine-induced alteration in the testes of adult Wistar rats · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. IO Onanuga, RB Ibrahim, A Amin, OB Akinola, GO Omotoso, MO Ogundele, CNB Tagoe, 426-433.

  6. Erythrocyte deformability, endothelin levels, and renal function in cyclosporin-treated renal transplant recipients: effects of intervention with fish oil and corn oil

    NARCIS (Netherlands)

    Schut, N. H.; Bilo, H. J.; Popp-Snijders, C.; Goedhart, P. T.; Wilmink, J. M.

    1993-01-01

    Twenty nine stable renal transplant recipients, 10 receiving cyclosporin, 10 cyclosporin-prednisolone and nine azathioprine-prednisolone were supplemented in a double blind randomization cross-over study with fish oil and corn oil for a period of 4 months each. Erythrocyte deformability was reduced

  7. Pulmonary Mycobacterium szulgai infection and treatment in a patient receiving anti-tumor necrosis factor therapy.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Janssen, M.; Ullmann, E.F.; Lange, W.; Haas, P. de; Dekhuijzen, P.N.R.; Soolingen, D. van

    2007-01-01

    BACKGROUND: A 54-year-old man with a 22-year history of rheumatoid arthritis and an 8-year history of chronic obstructive pulmonary disease presented with dyspnea on exertion, nonproductive cough and fatigue of 1 month's duration. His medication at presentation consisted of etanercept, azathioprine,

  8. Methotrexate nanoparticle delivery system for treatment of ...

    African Journals Online (AJOL)

    IBD were randomly assigned to treatment (MTX nanoparticles,15 mg/week) or control (azathioprine,. AZA, 2 mg/kg/day) group. Nanoparticles were ... multifactorial disorder characterized by an inappropriate immune response that includes .... version 9 (SPSS, Inc., Chicago, IL, USA) was used to conduct the statistical tests.

  9. Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

    Directory of Open Access Journals (Sweden)

    Elisa Liverani

    2013-01-01

    Full Text Available Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as “Gullo’s syndrome,” but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as “benign pancreatic hyperenzymemia”?

  10. Asymptomatic and persistent elevation of pancreatic enzymes in an ulcerative colitis patient.

    Science.gov (United States)

    Liverani, Elisa; Leonardi, Filippo; Castellani, Lucia; Cardamone, Carla; Belluzzi, Andrea

    2013-01-01

    Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as "Gullo's syndrome," but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as "benign pancreatic hyperenzymemia"?

  11. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J

    2005-01-01

    , 25 patients had been treated with high-dose IgG, and in 16 patients a splenectomy had been performed. Sixteen patients had been treated with azathioprine. Other treatments included, e.g., cyclosporine, danazol, cyclophosphamide, vincristine, interferon, and dexamethasone. The patients were treated...

  12. Prevention of postoperative recurrence in Crohn's disease

    NARCIS (Netherlands)

    D'Haens, G.

    1999-01-01

    Postoperative recurrence of Crohn's disease is often inevitable. Certain risk factors such as smoking, young age, and a perforating disease behavior have been identified. Patients with an enhanced risk profile should be treated with mesalamine or with azathioprine, the latter of which has higher

  13. Clinical Outcomes of Remission Induction Therapy for Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

    NARCIS (Netherlands)

    Miloslavsky, E. M.; Specks, U.; Merkel, P. A.; Seo, P.; Spiera, R.; Langford, C. A.; Hoffman, G. S.; Kallenberg, C. G. M.; St Clair, E. W.; Tchao, N. K.; Viviano, L.; Ding, L.; Sejismundo, L. P.; Mieras, K.; Ikle, D.; Jepson, B.; Mueller, M.; Brunetta, P.; Allen, N. B.; Fervenza, F. C.; Geetha, D.; Keogh, K.; Kissin, E. Y.; Monach, P. A.; Peikert, T.; Stegeman, C.; Ytterberg, S. R.; Stone, J. H.

    Objective. To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). Methods. The

  14. Treatment Algorithms in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Muangchan, Chayawee; van Vollenhoven, Ronald F; Bernatsky, Sasha R; Smith, C Douglas; Hudson, Marie; Inanç, Murat; Rothfield, Naomi F; Nash, Peter T; Furie, Richard A; Senécal, Jean-Luc; Chandran, Vinod; Burgos-Vargas, Ruben; Ramsey-Goldman, Rosalind; Pope, Janet E

    2015-09-01

    To establish agreement on systemic lupus erythematosus (SLE) treatment. SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement). Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and

  15. Pemphigus vulgaris – a report of three cases

    Science.gov (United States)

    Gharote, Harshkant P; Nair, Preeti P; Kasetty, Sowmya; Thomas, Shaji; Kulkarni, Abhay

    2012-01-01

    Pemphigus vulgaris (PV) is a potentially life-threatening illness that manifests in the mouth and on skin. In a majority of patients it affects the oral mucosa and is sometimes difficult to diagnose when only mucosal involvement is present. In an attempt to highlight the proper treatment plan of this potentially fatal disorder, the authors document a report of three cases. These patients were prescribed conventional steroids which brought about partial relief but early recurrence with discontinuation of the drug. Subsequent management of these patients with azathioprine along with corticosteroids improved the outcome of the disease with longer remission periods. In this case series, the steroid sparing effect of azathioprine was achieved successfully and hence needs to be considered as a primary drug in management of PV. PMID:22605597

  16. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  17. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz

    2011-01-01

    increased risk of preterm birth when women give birth 0-6 months after establishment of the diagnosis. It is considered whether the increased risk may be influenced by disease activity around the time of establishing the diagnosis. 2) No increased risk of giving birth to children with low birth weight...... in children of women with ulcerative colitis, ii) pharmacoepidemiological studies on the risk of adverse birth outcome after maternal azathioprine/6-mercaptopurine exposure in pregnancy, and the risk of congenital abnormalities in children fathered by men treated with azathioprine/6-mercaptopurine before......The clinical epidemiological studies included in this thesis fall into three parts. The first part includes studies on birth outcome in women with ulcerative colitis. The second part includes pharmacoepidemiological studies on birth outcome after anti-inflammatory drug therapy in pregnancy...

  18. Contemporary Management of Ulcerative Colitis.

    Science.gov (United States)

    Vanga, Rohini; Long, Millie D

    2018-03-27

    We discuss the newest evidence-based data on management of ulcerative colitis (UC). We emphasize risk-stratification, optimizing medical therapies, and surgical outcomes of UC. Recent medical advances include introduction of novel agents for UC. Vedolizumab, an anti-adhesion molecule, has demonstrated efficacy in moderate to severe UC. Tofacitinib, a small molecule, has also demonstrated efficacy. Data on optimization of infliximab show the superiority of combination therapy with azathioprine over monotherapy with infliximab or azathioprine alone. Data on anti-tumor necrosis factor-alpha (anti-TNF) therapeutic drug monitoring also hold promise, as do preliminary data on the dose escalation of infliximab in severe hospitalized UC. Surgical outcome data are reassuring, with new fertility data showing the effectiveness of in vitro fertilization. UC management is multi-disciplinary and changing. While novel therapies hold promise, better optimization of our current arsenal will also improve outcomes.

  19. Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

    Science.gov (United States)

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  20. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  1. Innovative therapeutics for inflammatory bowel disease

    OpenAIRE

    Yamamoto-Furusho, Jesus K

    2007-01-01

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn’s disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different le...

  2. Lupus cystitis: An unusual presentation of systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    S Mukhopadhyay

    2014-01-01

    Full Text Available Lupus cystitis is a rare complication of systemic lupus erythematosus (SLE and occurs in association with gastrointestinal symptoms. This rare disorder has been reported mainly from Japan. We report a 20 year old female who diagnosed as having SLE associated with paralytic ileus and chronic interstitial cystitis. Treatment with intravenous methylprednisolone, cyclophosphamide pulse therapy followed by oral prednisolone and azathioprine led to amelioration of manifestations. Later she developed lupus nephritis which was treated with mycophenolate mofetil.

  3. Author Details

    African Journals Online (AJOL)

    Jallouli, M. Vol 20, No 1 (2015) - Articles Association sarcoïdose et maladie de Horton: à propos d'un cas. Abstract PDF · Vol 20, No 1 (2015) - Articles Entérite lupique récidivante améliorée par Azathioprine Abstract. ISSN: 1937-8688. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  4. Infliximab-induced intertriginous psoriasis in patient with Crohn's disease

    OpenAIRE

    Mola, Federica; Motolese, Alberico

    2011-01-01

    Tumor necrosis factor-α (TNFα) inhibition is an effective treatment of moderate-to-severe psoriasis and other diseases (rheumatoid arthritis, ankylosing spondylitis, psoriasis or Crohn’s disease). We report a case of a 32- years-old patient affected by Crohn’s disease since the age of 25 who started infliximab infusion after four years of treatment with prednisone and azathioprine per os without improvement. After the fifth infusion of infliximab, he developed a form of intertriginous psorias...

  5. Induction d'un processus d'instabilité des microsatellites du génome dans des modèles murin et cellulaire : intérêt physiopathologique et clinique

    OpenAIRE

    Bodo , Sahra

    2014-01-01

    Inactivation of the MMR (mismatch repair) system promotes the oncogenic process of microsatellite instability (MSI). During my PhD, I firstly investigated the role of azathioprine (Aza) in the induction of MSI tumors in mice. Epidemiological studies reported a correlation between the occurrence of late MSI cancers in humans and long-term treatment with this immunosuppressant whose cytotoxicity was shown in vitro to be mediated by MMR activity. Using a dose-response study, I observed the occur...

  6. Antilymphocyte antiserum effect on incidence of spontaneous malignancy. I. Long term treated mice.

    Science.gov (United States)

    Pirofsky, B; Dawson, P J

    1976-01-01

    Long term potent immunosuppression was administered to normal 7-week-old BALB/c mice without exogenous neoplastic induction. Antilymphocyte antiserum was given biweekly for 8 weeks and azathioprine daily for 347 days. Significant immunodepression was demonstrated after 348 days of theraphy. After 2 years, all animals were sacrificed and examined for neoplasia. There was no evidence that such immunodepression increased the incidence of spontaneous malignancy. The study suggests that immunosuppressive therapy is not inately oncogenic.

  7. Induction of immunological tolerance in the pig-to-baboon xenotransplantation model : studies aimed at achieving mixed hematopoietic chimerism and preventing associated thrombotic complications

    OpenAIRE

    Alwayn, Ian

    2001-01-01

    textabstractThe outcome of clinical organ transplantation has dramatically improved since the introduction of cyclosporine (CyA) in 1979 and of other, more recently introduced, immunosuppressive agents such as azathioprine, mycophenolate mofetil, tacrolimus and sirolimus. Furthermore, due to more refined surgical techniques and peri operative management, prolonged survival of allografts is achieved. Due to its relative success, the inclusion criteria for potential organ transplant recipients ...

  8. [Successful treatment of panarteritis nodosa with low-dose methotrexate therapy].

    Science.gov (United States)

    Brody, M; Böhm, I; Biwer, E; Bauer, R

    1994-07-01

    We report on a 45-year-old male patient who presented a classic polyarteritis nodosa (PAN). The clinical course extended over 7 years. In spite of 2 years immunosuppressive therapy with azathioprine and methylprednisolone the course was progressive. Low-dose methotrexate therapy was the only treatment that controlled the disease, leading to rapid clinical and histopathological remission. In low concentrations methotrexate acts as an IL-1 inhibitor, and it obviously suppresses the pathogenetic mechanism of PAN.

  9. Annual Progress Report of the Department of Clinical Investigation, Reports Control Symbol MED-300(R-1), Fiscal Year 1992

    Science.gov (United States)

    1992-10-01

    Between Family History and Infantile Apnea (C) TAMC Lupien, Alfred E. 62 41H92 Factors Affecting Field Utilization of Pulse Oximetry NUTRITION CARE... Tuberculosis and M Avium Complexes (C) TAMC Gunn, Bruce A. 68 18L91 Biotyping of Coagulase-Negative Staphylococci (CNS) in the Clinical Laboratory (C) (PR) (SP... Infantile Diarrhea TAMC Banks, Richard A. 73 4H87 Immunosuppressive Therapy with Methylprednisolone, Prednisone, and Azathioprine in Patients with Newly

  10. Immunomodulatory Activity of Chlorophytum borivilianum Sant. F

    OpenAIRE

    Thakur, Mayank; Bhargava, Shilpi; Dixit, V. K.

    2007-01-01

    Chlorophytum borivilianum Santapau & Fernandes (Liliaceae) is a very popular herb in traditional Indian medicine and constitute a group of herbs used as ‘Rasayan’ or adaptogen. Ethanolic extract of the roots and its sapogenin were evaluated for their immunomodulatory activity. Effect of azathioprine-induced myelosuppresion and administration of extracts on hematological and serological parameters was determined. Administration of extracts greatly improved survival against Candida albicans inf...

  11. Current and emerging treatments for the management of myasthenia gravis

    Science.gov (United States)

    Sathasivam, Sivakumar

    2011-01-01

    Myasthenia gravis is an autoimmune neuromuscular disorder. There are several treatment options, including symptomatic treatment (acetylcholinesterase inhibitors), short-term immunosuppression (corticosteroids), long-term immunosuppression (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil, rituximab, tacrolimus), rapid acting short-term immunomodulation (intravenous immunoglobulin, plasma exchange), and long-term immunomodulation (thymectomy). This review explores in detail these different treatment options. Potential future treatments are also discussed. PMID:21845054

  12. Lupus cystitis: An unusual presentation of systemic lupus erythematosus

    OpenAIRE

    Mukhopadhyay, S.; Jana, S.; Roy, M. K.; Chatterjee, A.; Sarkar, A.; Mazumdar, S.; Mukherjee, P.; Mukhopadhyay, J.

    2014-01-01

    Lupus cystitis is a rare complication of systemic lupus erythematosus (SLE) and occurs in association with gastrointestinal symptoms. This rare disorder has been reported mainly from Japan. We report a 20 year old female who diagnosed as having SLE associated with paralytic ileus and chronic interstitial cystitis. Treatment with intravenous methylprednisolone, cyclophosphamide pulse therapy followed by oral prednisolone and azathioprine led to amelioration of manifestations. Later she develop...

  13. Lupus cystitis: An unusual presentation of systemic lupus erythematosus.

    Science.gov (United States)

    Mukhopadhyay, S; Jana, S; Roy, M K; Chatterjee, A; Sarkar, A; Mazumdar, S; Mukherjee, P; Mukhopadhyay, J

    2014-09-01

    Lupus cystitis is a rare complication of systemic lupus erythematosus (SLE) and occurs in association with gastrointestinal symptoms. This rare disorder has been reported mainly from Japan. We report a 20 year old female who diagnosed as having SLE associated with paralytic ileus and chronic interstitial cystitis. Treatment with intravenous methylprednisolone, cyclophosphamide pulse therapy followed by oral prednisolone and azathioprine led to amelioration of manifestations. Later she developed lupus nephritis which was treated with mycophenolate mofetil.

  14. Clinical Trial of FK 506 Immunosuppression in Adult Cardiac Transplantation

    OpenAIRE

    Armitage, John M.; Kormos, Robert L.; Morita, Shigeki; Fung, John; Marrone, Gary C.; Hardesty, Robert L.; Griffith, Bartley P.; Starzl, Thomas E.

    1992-01-01

    The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparabl...

  15. Capillary Electrophoresis Hyphenated with Mass Spectrometry for Determination of Inflammatory Bowel Disease Drugs in Clinical Urine Samples

    Directory of Open Access Journals (Sweden)

    Katarína Maráková

    2017-11-01

    Full Text Available Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE hyphenated with tandem mass spectrometry (MS/MS for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol. The optimized CE-MS/MS conditions provided a very efficient and stable system for the separation and sensitive detection of these drugs in human urine matrices. The developed method was successfully applied for the assay of the targeted drugs and their selected metabolites in urine samples collected from patients suffering from inflammatory bowel disease (IBD and receiving azathioprine therapy. The developed CE-MS/MS method, due to its reliability, short analysis time, production of complex clinical profiles, and favorable performance parameters, evaluated according to FDA guidelines for bioanalytical method validation, is proposed for routine clinical laboratories to optimize thiopurine therapy, estimate enzymatic activity, and control patient compliance with medication and co-medication.

  16. Complicated Crohn's-like colitis, associated with Hermansky-Pudlak syndrome, treated with Infliximab: a case report and brief review of the literature

    Directory of Open Access Journals (Sweden)

    Kouklakis George

    2007-12-01

    Full Text Available Abstract Introduction Hermansky-Pudlak syndrome (HPS is a rare autosomal recessive inherited disorder consisting of a triad of albinism, increased bleeding tendency secondary to platelet dysfunction, and systemic complications associated with ceroid depositions within the reticuloendothelial system. HPS has been associated with gastrointestinal (GI complications related to chronic granulomatous colitis with pathologic features suggestive of Crohn's disease. This colitis can be severe and has been reported to be poorly responsive to medical therapies including antibiotics, corticosteroids, sulfasalazine, mesalamine and azathioprine. Case presentation We report a patient with HPS which was complicated by inflammatory bowel disease with clinical and pathologic features of Crohn's disease, refractory to antibiotics, corticosteroids and azathioprine. A trial of infliximab was attempted and repeated infusions produced a complete response. Conclusion The occurrence of ileitis and perianal lesions and also the histopathological findings in our case suggest that HPS and Crohn's disease may truly be associated. Given this similarity and the failure of the standard medical therapy of corticosteroids and azathioprine, our patient received infliximab with marked clinical improvement.

  17. Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs.

    Science.gov (United States)

    Quaglio, Ana Elisa Valencise; Castilho, Anthony Cesar Souza; Di Stasi, Luiz Claudio

    2015-09-01

    The etiopathogenesis of inflammatory bowel disease (IBD) is unclear and further understanding of the mechanisms that regulate intestinal barrier integrity and function could give insight into its pathophysiology and mode of action of current drugs used to treat human IBD. Therefore, we investigated how intestinal inflammation affects Map kinase gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. Macroscopic parameters of lesion, biochemical markers (myeloperoxidase, alkaline phosphatase and glutathione), gene expression of 13Map kinases, and histologic evaluations (optic, electronic scanning and transmission microscopy) were performed in rats with colonic inflammation induced by trinitrobenzenesulphonic (TNBS) acid. The colonic inflammation was characterized by a significant increase in the expression of Mapk1, Mapk3 and Mapk9 accompanied by a significant reduction in the expression ofMapk6. Alterations inMapk expression induced by TNBS were differentially counteracted after treatment with sulphasalazine, prednisolone and azathioprine. Protective effects were also related to the significant reduction of oxidative stress, which was related to increase Mapk1/3 expressions, which were reduced after pharmacological treatment. Mapk1, Mapk3,Mapk6 and Mapk9 gene expressionswere affected by colonic inflammation induced by TNBS in rats and counteracted by sulphasalazine, prednisolone and azathioprine treatments, suggesting that these genes participate in the pharmacological response produced for these drugs.

  18. Infliximab versus Cyclosporine Treatment for Severe Corticosteroid-Refractory Ulcerative Colitis: A Korean, Retrospective, Single Center Study

    Science.gov (United States)

    Kim, Eun Hye; Kim, Duk Hwan; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2015-01-01

    Background/Aims In patients with corticosteroid-refractory ulcerative colitis (UC), cyclosporine or infliximab may be added to the treatment regimen to induce remission. Here, we aimed to compare the efficacy of cyclosporine and infliximab. Methods Between January 1995 and May 2012, the medical records of 43 patients with corticosteroid-refractory UC who received either infliximab or cyclosporine as a rescue therapy at a tertiary care hospital in Korea were reviewed. Results Among the 43 patients, 10 underwent rescue therapy with cyclosporine and the remaining 33 patients received infliximab. A follow-up of 12 months was completed for all patients. The colectomy rate at 12 months was 30% and 3% in the cyclosporine and the infliximab groups, respectively (p=0.034). However, the Cox proportional hazard model indicated that the treatment of rescue therapy was not an independent associate factor for preventing colectomy (p=0.164). In the subgroup analysis, infliximab with azathioprine was superior to cyclosporine for preventing colectomy (hazard ratio of infliximab with azathioprine compared with cyclosporine only, 0.073; 95% confidence interval, 0.008 to 0.629). Conclusions No difference between infliximab and cyclosporine with respect to preventing colectomy was noted. However, infliximab with azathioprine may be more effective than cyclosporine alone for preventing colectomy. PMID:25473080

  19. Effect of infliximab top-down therapy on weight gain in pediatric Crohns disease.

    Science.gov (United States)

    Kim, Mi Jin; Lee, Woo Yong; Choi, Kyong Eun; Choe, Yon Ho

    2012-12-01

    This retrospective-medical-record review was conducted to evaluate effect of infliximab therapy, particularly with a top-down strategy, on the nutritional parameters of children with Crohns disease (CD). 42 patients who were diagnosed with Crohns disease at the Pediatric Gastroenterology center of a tertiary care teaching hospital and achieved remission at two months and one year after beginning of treatment were divided into four subgroups according to the treatment regimen; azathioprine group (n = 11), steroid group (n = 11), infliximab top-down group (n = 11) and step-up group (n = 9). Weight, height, and serum albumin were measured at diagnosis, and then at two months and one year after the initiation of treatment. At 2 months, the Z score increment for weight was highest in the steroid group, followed by the top-down, step-up, and azathioprine groups. At one year, the Z score increment was highest in top-down group, followed by steroid, azathioprine, and step-up group. There were no significant differences between the four groups in Z score increment for height and serum albumin during the study period. The top-down infliximab treatment resulted in superior outcome for weight gain, compared to the step-up therapy and other treatment regimens.

  20. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of tiopurines in inflammatory bowel disease.

    Science.gov (United States)

    Bermejo, Fernando; Aguas, Mariam; Chaparro, María; Domènech, Eugeni; Echarri, Ana; García-Planella, Esther; Guerra, Iván; Gisbert, Javier P; López-Sanromán, Antonio

    2018-03-01

    Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Coexisting Crohn’s Disease and Takayasu’s Arteritis in Two Patients Treated with Anti-TNF-α Therapies

    Directory of Open Access Journals (Sweden)

    S. Ratuapli

    2010-02-01

    Full Text Available Crohn’s disease (CD and Takayasu’s arteritis (TA are inflammatory granulomatous autoimmune disorders. Simultaneous occurrence of CD and TA in the same individual is rare. We report two cases treated with biologic agents. Case 1: A 16-year-old male presented with abdominal pain, nausea, vomiting. CT angiogram showed thickening of the terminal ileum, wall thickening and narrowing of multiple large and medium arteries including aorta and left common carotid. Colonoscopy with biopsy of the stenotic ileocecal valve confirmed CD. Resected carotid artery pathology was consistent with TA. Treatment was initially begun with prednisone, then methotrexate was started followed by infliximab. Due to side effects, methotrexate was switched to azathioprine. He remained asymptomatic. Case 2: A 38-year-old male with well-characterized Crohn’s ileocolitis for 15 years, who had been treated with prednisone, mesalamine, sulfasalazine, and azathioprine presented with chest, upper back and abdominal pain. CT angiogram showed vasculitis of large and medium arteries, with stenosis of the right renal artery, and wall thickening of the sigmoid colon. He was diagnosed with TA. He underwent treatment with infliximab and adalumimab on different occasions, which were later discontinued due to fever, bacteremia and complications from sepsis. He remained on prednisone and azathioprine. In these two patients with both CD and TA the diagnoses were confirmed by imaging and pathologic findings. Both patients developed vascular complications. Tumor necrosis factor inhibitor therapy was effective in one patient but discontinued in the other due to infection. Further research into the association of CD and TA may provide clues to their etiologies and guide effective interventions.

  2. Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis and M. tuberculosis

    Directory of Open Access Journals (Sweden)

    Knodel Marvin H

    2003-06-01

    Full Text Available Abstract Background Tuberculosis remains a serious world-wide health threat which requires the characterisation of novel drug targets for the development of future antimycobacterials. One of the key obstacles in the definition of new targets is the large variety of metabolic alterations that occur between cells in the active growth and chronic/dormant phases of tuberculosis. The ideal biochemical target should be active in both growth phases. Methionine adenosyltransferase, which catalyses the formation of S-adenosylmethionine from methionine and ATP, is involved in polyamine biosynthesis during active growth and is also required for the methylation and cyclopropylation of mycolipids necessary for survival in the chronic phase. Results The gene encoding methionine adenosyltransferase has been cloned from Mycobacterium tuberculosis and the model organism M. smegmatis. Both enzymes retained all amino acids known to be involved in catalysing the reaction. While the M. smegmatis enzyme could be functionally expressed, the M. tuberculosis homologue was insoluble and inactive under a large variety of expression conditions. For the M. smegmatis enzyme, the Vmax for S-adenosylmethionine formation was 1.30 μmol/min/mg protein and the Km for methionine and ATP was 288 μM and 76 μM respectively. In addition, the enzyme was competitively inhibited by 8-azaguanine and azathioprine with a Ki of 4.7 mM and 3.7 mM respectively. Azathioprine inhibited the in vitro growth of M. smegmatis with a minimal inhibitory concentration (MIC of 500 μM, while the MIC for 8-azaguanine was >1.0 mM. Conclusion The methionine adenosyltransferase from both organisms had a primary structure very similar those previously characterised in other prokaryotic and eukaryotic organisms. The kinetic properties of the M. smegmatis enzyme were also similar to known prokaryotic methionine adenosyltransferases. Inhibition of the enzyme by 8-azaguanine and azathioprine provides a starting

  3. Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation.

    Science.gov (United States)

    Quaglio, Ana E V; Castilho, Anthony C S; Di Stasi, Luiz C

    2015-11-15

    Etiopathogenesis of inflammatory bowel disease is unclear and results from a complex interplay of genetic, microbial, environmental and immune factors. Elucidating the mechanisms that drive IBD depends on the detailed characterization of human inflammatory mediators in animal models. Therefore, we studied how intestinal inflammation affects heparanase, NF-κB and Hsp70 gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. Moreover, we investigated the relationships among these genes with colonic cytokines levels (IL-1β, TNF-α, IL-6, INF-γ and IL-10) and oxidative stress that have fundamental role in IBD. Macroscopic parameters (diarrhea, extension of lesion, colonic weight/length ratio and damage score), biochemical markers (myeloperoxidase and alkaline phosphatase activities, and glutathione, IL-1β, TNF-α, IL-6, INF-γ and IL-10 levels), gene expressions (heparanase, NF-κB and Hsp70), and microscopic evaluations (optic, electronic scanning and transmission microscopic) were performed in rats. Expression of heparanase, Hsp70 and NF-κB and oxidative stress were increased by inflammatory process and differentially modulated by sulphasalazine, prednisolone and azathioprine treatments. Protective effects of drugs were also related to differential modulation of cytokine changes induced by inflammatory process, showing different mechanisms to control inflammation. Heparanase, NF-κB and Hsp70 gene expression participate in the inflammatory response induced by TNBS and represent pharmacological targets of the intestinal anti-inflammatory drugs. In addition, current drugs used to treat IBD (sulphasalazine, prednisolone and azathioprine) differentially modulate heparanase, NF-κB and Hsp70 gene expression, cytokine production and oxidative stress.

  4. Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

    Science.gov (United States)

    Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

    2017-11-01

    We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case.

  5. Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications.

    Science.gov (United States)

    Ban, Lu; Tata, Laila Jal; Fiaschi, Linda; Card, Timothy

    2014-01-01

    Concerns persist about the risk of major congenital anomalies in children of women with inflammatory bowel disease (IBD), and whether medication use affects risk. We assessed these risks, and variations in use of medications by women with IBD before, during, and after pregnancy. We accessed data on children born to women 15-45 y old from 1990 through 2010, using a mother-child linked dataset from an electronic database of primary care records containing medical diagnoses, events, and drug prescriptions from across the United Kingdom. We identified pregnant women with IBD, and all prescriptions for 5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were extracted from their primary care records. We calculated risks of major congenital anomaly in children of mothers with and without IBD, and in children exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids during their first trimester of fetal development. Logistic regression with a generalized estimating equation was used to provide risk estimates adjusted for confounders. We calculated proportions of women taking medications before, during, and after pregnancy and assessed whether cessation was associated with subsequent disease flares. Risks of a major congenital anomaly in 1703 children of mothers with IBD and 384,811 children of mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In children of women with IBD, the adjusted odds ratios of a major congenital anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5-aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI, 0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or genital anomalies were found in children of women with IBD; 31.2% of women discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6-mercaptopurine in early pregnancy

  6. The Use of Budesonide in the Treatment of Autoimmune Hepatitis in Canada

    Directory of Open Access Journals (Sweden)

    Iman Zandieh

    2008-01-01

    Full Text Available BACKGROUND: Autoimmune hepatitis (AIH is a chronic inflammatory disease that is successfully treated with prednisone and/or azathioprine immunosuppressive therapy in 70% to 80% of patients. The remaining patients are intolerant or refractory to these standard medications. Budesonide, a synthetic glucocorticoid, undergoes a high degree of first-pass metabolism, reducing its systemic bioavailability, and has a 15-fold greater affinity for the glucocorticoid receptor than prednisolone. Budesonide may be a potentially useful systemic steroid-sparing immunosuppressive agent in the treatment of AIH.

  7. Acute dapsone overdose: the effects of continuous veno-venous haemofiltration on the elimination of dapsone.

    Science.gov (United States)

    Masurkar, V A; Edstein, M D; Gorton, C J; Anstey, C M

    2011-11-01

    A 15-year-old girl presented after intentional ingestion of dapsone (7.2 g) and small quantities of azathioprine, methotrexate and prednisolone. The resulting methaemoglobinaemia and lactic acidosis persisted despite treatment with methylene blue, multiple-dose activated charcoal and ascorbic acid. Continuous veno-venous haemofiltration for 75 hours was used to treat the dapsone overdose. The patient's serum dapsone concentrations were measured during and after continuous veno-venous haemofiltration. The rate of elimination of dapsone was over three times higher during, compared to after, continuous veno-venous haemofiltration. Continuous renal replacement therapy successfully reduced toxic dapsone concentrations in this patient with a good outcome.

  8. Efficacy of oral sirolimus as salvage therapy in refractory lichen planus associated with immune deficiency.

    Science.gov (United States)

    Mahévas, T; Bertinchamp, R; Battistella, M; Reygagne, P; Oksenhendler, E; Fieschi, C; Bachelez, H

    2018-03-24

    Lichen planus (LP) remains often difficult-to-treat in its chronic, severe and erosive forms, requiring use of immunomodulatory (acitretin, PUVA, and extracorporeal photochemotherapy (EPC)) or off label immunosuppressive strategies (cyclosporine, azathioprine). 1,2,3 However, the pathogenic role of an HPV-specific T-cell response in chronic LP, and the increased risk of neoplasia, especially in its severe mucosal forms, both support the use of T-cell-targeting immunosuppressants with antineoplastic attributes, such as mammalian target of rapamycin (mTOR) inhibitors 4,5 . This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Dacryoadenitis with Ptosis and Diplopia as the Initial Presentation of Granulomatosis with Polyangiitis.

    Science.gov (United States)

    Hibino, Makoto; Kondo, Tetsuri

    2017-10-01

    A 77-year-old Japanese woman presented to an ophthalmologist with an erythematous swollen upper eyelid and diplopia which was initially diagnosed to be idiopathic dacryoadenitis on the basis of a histological evaluation of an orbital mass that was in remission following a 3.5-month period of systemic corticosteroid therapy. She subsequently developed respiratory symptoms, and was finally diagnosed with systemic granulomatosis with polyangiitis (GPA) based on the clinical and histological features. She was successfully treated with corticosteroids and azathioprine. Dacryoadenitis in the form of an orbital inflammatory pseudotumor may be an initial presenting feature of GPA, sometimes as the limited phenotype, and occasionally progressing to systemic disease.

  10. Gravidez após transplante hepático

    Directory of Open Access Journals (Sweden)

    Júlio Cezar Uili Coelho

    Full Text Available The objective of the present study is to report a sucessful pregnancy in a 28 year-old female who underwent an orthotopic liver transplantation two years ago due to type I auto immune he patitis. Patient was taking cyclosporin, prednisone and azathioprine for maintenance immunossupression and had good graft function during all the pregnancy. The liver function tests were normal during the pregnancy. Fetal growth was monitored by ultrasonographic examination and showed normal development. At the end of the third trimester, she was subjected to a cesarean bearing a healthy girl weighting 2,320 kg. She was discharged with normal liver functions tests and no complications.

  11. Vasculitis and Pregnancy.

    Science.gov (United States)

    Machen, Leah; Clowse, Megan E B

    2017-05-01

    Vasculitis is more often a disease of women beyond their reproductive years, leaving the challenges of pregnancy management difficult to study. Pregnancy complications, including pregnancy loss and preterm birth, are higher among women with all forms of vasculitis. It seems that controlling the disease before pregnancy may improve the chances of pregnancy success. Many medications used for vasculitis are considered low risk in pregnancy, including prednisone, colchicine, azathioprine, and tumor necrosis factor inhibitors. Cyclophosphamide, methotrexate, and mycophenolate mofetil should be avoided in pregnancy. Controlling disease with low-risk medications may allow women with vasculitis to have the pregnancies they desire. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to a1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  13. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  14. MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 2

    DEFF Research Database (Denmark)

    Jarius, Sven; Ruprecht, Klemens; Kleiter, Ingo

    2016-01-01

    followed a multiphasic course in 80% (median time-to-first-relapse 5months; annualized relapse rate 0.92) and resulted in significant disability in 40% (mean follow-up 75±46.5months), with severe visual impairment or functional blindness (36%) and markedly impaired ambulation due to paresis or ataxia (25...... leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period...

  15. [Allergo-immunology. Clinical immunology].

    Science.gov (United States)

    Chizzolini, C

    2012-01-11

    The past year has been characterized by significant novelties from the point of view of the clinical immunologist. With the BLISS 52 study showing that belimumab has the ability to decrease the activity of systemic lupus erythematosus (SLE) resistant to conventional therapy an important step towards the control of this difficult disease has been carried forward. In addition, the long-term results of the ALMS study have demonstrated that mycophenolate mofetil is superior to azathioprine in maintaining the remission in patients with severe lupus nephritis. Furthermore, the results of the RAVE and RITUXVASC studies have documented that rituximab is a valid alternative to cyclophosphamide in the control of ANCA associated vasculitis.

  16. Recommendations for use of everolimus after heart transplantation: results from a Latin-American Consensus Meeting.

    Science.gov (United States)

    Bocchi, E A; Ahualli, L; Amuchastegui, M; Boullon, F; Cerutti, B; Colque, R; Fernandez, D; Fiorelli, A; Olaya, P; Vulcado, N; Perrone, S V

    2006-04-01

    Despite improvements during the last decades, heart transplantation remains associated with several medical complications, which limit clinical outcomes: acute rejection with hemodynamic compromise, cytomegalovirus (CMV) infections, allograft vasculopathy, chronic renal failure, and neoplasias. Everolimus, a proliferation signal inhibitor, represents a new option for adjunctive immunosuppressive therapy. Everolimus displays better efficacy in de novo heart transplant patients than azathioprine for prophylaxis of biopsy-proven acute rejection episodes of at least ISHLT grade 3A (P Latin America produced recommendations for everolimus use in daily practice based on available data and their own experience.

  17. Atopic dermatitis: Kids are not just little people.

    Science.gov (United States)

    Awasthi, Smita; Rothe, Marti Jill; Eichenfield, Lawrence F

    2015-01-01

    The approach to children and adults with atopic dermatitis is similar. In both age groups, failure to respond to conventional therapy should prompt evaluation for complicating factors such as secondary infection and secondary ACD. Immunologic, metabolic, genetic, and nutritional disorders should be considered in the differential diagnosis of refractory pediatric atopic dermatitis. Cutaneous T cell lymphoma (CTCL), cutaneous drug reactions, other spongiotic dermatoses, psoriasis, dermatomycosis, and infestations should be considered in the differential of refractory atopic dermatitis in adults. Systemic therapies prescribed to both children and adults with severe atopic dermatitis include oral corticosteroids, cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil. Copyright © 2015. Published by Elsevier Inc.

  18. [Multiple sclerosis. Therapeutic nihilism is the wrong approach here].

    Science.gov (United States)

    Voltz, R; Goebels, N; Jarius, S; Hohlfeld, R

    2002-05-06

    The standard treatment for acute multiple sclerosis relapses continues to be the intravenous administration of high-dose methylprednisolone. For prophylactic purposes, immunomodulatory therapy with interferon beta or glatiramer acetate, immunoglobulins or azathioprine. Studies have shown that interferon beta not only reduces the frequency of relapses by one-third, but also significantly delays the second relapse, provided it is administrated early, that is, immediately following the first relapse. The reduction in the patient's quality of life caused by the illness can be appreciably improved by a whole series of symptomatic treatments. The ideal situation is a cooperative effort by an interdisciplinary team.

  19. Immune-mediated rippling muscle disease and myasthenia gravis.

    Science.gov (United States)

    Bettini, Mariela; Gonorazky, Hernan; Chaves, Marcelo; Fulgenzi, Ernesto; Figueredo, Alejandra; Christiansen, Silvia; Cristiano, Edgardo; Bertini, Enrico S; Rugiero, Marcelo

    2016-10-15

    Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. IMMUNOSUPPRESSEURS ET MICI. A propos d'une série hospitalière au niveau du Service d' Hépato-gastroentérologie, CHU Tlemcen.

    OpenAIRE

    BENREBRIT, Houria; BENMOKRANE, Lamia

    2013-01-01

    Les immunosuppresseurs occupent aujourd'hui une place importante dans le traitement des MICI. L'Azathioprine constitue la principale classe d'immunosuppresseurs utilisée. Il permet d'obtenir une stabilisation de la maladie dans plus de la moitié des cas. Malgré ces succès thérapeutiques, un pourcentage non négligeable de malades est en échec thérapeutique associé à des effets secondaires indésirables qui aboutissent à des réductions des doses ou à une interruption du traitement...

  1. Generalized morphea/eosinophilic fasciitis overlap after epoxy exposure

    Directory of Open Access Journals (Sweden)

    Warren H. Chan, MS

    2018-03-01

    Full Text Available Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF, or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies—ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab—none of which led to a significant response. The refractory nature of this disease warrants vigilance in its association with epoxy exposure.

  2. Behçet's syndrome presenting with chronic periodontitis: a case report.

    Science.gov (United States)

    Wagaiyu, E G; Chindia, M L

    1992-10-01

    Behçet's syndrome is a disease of uncertain aetiology characterised by recurrent oral and genital ulcerations, ocular lesions and skin lesions. Although cases of this syndrome have been reported almost worldwide, the literature did not reveal any reports from this region. Management of this disorder is mainly palliative. However several treatment regimens have been tried. Following are some of the treatments considered effective. Azathioprine, corticosteroids, chlorambucil, transfusions of fresh blood or plasma and fibrinolytic therapy with phenformin and ethyloestrenol. The importance of multi-disciplinary management of such patients is emphasized.

  3. Rosai-Dorfman Disease with nodal and extranodal involvements: A case report

    Directory of Open Access Journals (Sweden)

    Mehri Najafi-Sani

    2011-01-01

    Full Text Available Rosai-Dorfman disease (RDD is a rare lymphoproliferative disorder with nodal and extranodal involvements. Here we report a case of RDD in a 15-year-old female who presented with epigastric pain, fatigue, Raynaud phenomenon in fingers, submandibular lymphadenopathy, proptosis, hepatosplenomegaly, and round shape painless patches on the extensor surfaces. Histological examination of the submandibular lymph nodes and skin biopsy demonstrated evidences of RDD. Patient was treated with prednisone and thereafter, with azathioprine. After one year, prednisone was discontinued and all of the symptoms and signs, except proptosis, were resolved. This report highlights the extranodal manifestations of RDD. The presentation, differential diagnosis, and treatment are discussed.

  4. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

    Science.gov (United States)

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona

    2015-03-01

    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  5. The Flare Up of Catastrophic Antiphospholipid Syndrome: a Report of an Immunosuppressive Withdrawal-Induced Case

    Directory of Open Access Journals (Sweden)

    Sayyed Gholamreza Mortazavimoghaddam

    2011-09-01

    Full Text Available Antiphospholipid syndrome (APS is a systemic disease that causes venous and arterial thrombosis in virtually any organ. Sometimes it is complicated into pulmonary infarction and cavitation, pulmonary hypertension, and catastrophic course with high morbidity and mortality. The present case is a 35-year-old woman with one episode of postpartum deep veins thrombosis (DVT 12 years earlier and the second one after the second labor two years later. In spite of usual therapy for each episode of DVT, the condition had progressed into severe pulmonary hypertension. The diagnosis of primary APL syndrome was confirmed four years ago. She had been on warfarin, low dose of steroid, and azathioprine since the diagnosis of APL syndrome. After one year treatment with steroid and azathiprine the patient showed progressive well being; however, because of hyperglycemia the steroid tapered and discontinued. She had several attacks of paroxismal atrial tachycardia in the last year. On the last time, she presented with severe dyspnea, hemoptesis, and lower limbs edema. Chest radiography and Lung CT scan demonsterated the presence of lung cavitations. Because of high suspicious for fungal pulmonary infection, azathioprine was also discontinued. However, constellation renal failure, hemodynamic instability, and confusion caused the patient to succumb to death. The definite diagnosis of lung cavitations was not obtained

  6. Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients.

    Science.gov (United States)

    Zakharova, Elena V; Makarova, Tatiana A; Zvonova, Elena V; Anilina, Alina M; Stolyarevich, Ekaterina S

    2016-01-01

    Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47) of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2-4 due to the serological abnormalities only. We conclude that (1) initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2) complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3) the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission.

  7. Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients

    Directory of Open Access Journals (Sweden)

    Elena V. Zakharova

    2016-01-01

    Full Text Available Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47 of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2–4 due to the serological abnormalities only. We conclude that (1 initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2 complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3 the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission.

  8. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis

    Science.gov (United States)

    Bertsias, George K; Tektonidou, Maria; Amoura, Zahir; Aringer, Martin; Bajema, Ingeborg; Berden, Jo H M; Boletis, John; Cervera, Ricard; Dörner, Thomas; Doria, Andrea; Ferrario, Franco; Floege, Jürgen; Houssiau, Frederic A; Ioannidis, John P A; Isenberg, David A; Kallenberg, Cees G M; Lightstone, Liz; Marks, Stephen D; Martini, Alberto; Moroni, Gabriela; Neumann, Irmgard; Praga, Manuel; Schneider, Matthias; Starra, Argyre; Tesar, Vladimir; Vasconcelos, Carlos; van Vollenhoven, Ronald F; Zakharova, Helena; Haubitz, Marion; Gordon, Caroline; Jayne, David; Boumpas, Dimitrios T

    2012-01-01

    Objectives To develop recommendations for the management of adult and paediatric lupus nephritis (LN). Methods The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus. Results Immunosuppressive treatment should be guided by renal biopsy, and aiming for complete renal response (proteinuria treatment for patients with class III–IVA or A/C (±V) LN according to the International Society of Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. In patients with adverse clinical or histological features, CY can be prescribed at higher doses, while azathioprine is an alternative for milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in combination with oral glucocorticoids is recommended as initial treatment. In patients improving after initial treatment, subsequent immunosuppression with MPA or azathioprine is recommended for at least 3 years; in such cases, initial treatment with MPA should be followed by MPA. For MPA or CY failures, switching to the other agent, or to rituximab, is the suggested course of action. In anticipation of pregnancy, patients should be switched to appropriate medications without reducing the intensity of treatment. There is no evidence to suggest that management of LN should differ in children versus adults. Conclusions Recommendations for the management of LN were developed using an evidence-based approach followed by expert consensus. PMID:22851469

  9. Duodenal villous atrophy: a cause of chronic diarrhea after solid-organ transplantation.

    Science.gov (United States)

    Weclawiak, H; Ould-Mohamed, A; Bournet, B; Guilbeau-Frugier, C; Fortenfant, F; Muscari, F; Sallusto, F; Dambrin, C; Esposito, L; Guitard, J; Abbal, M; Rostaing, L; Kamar, N

    2011-03-01

    Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Pemphigus in North-Western Yemen: A therapeutic study of 75 cases.

    Science.gov (United States)

    Khatri, Mishri Lal

    2016-01-01

    The incidence of pemphigus, though not documented, seems to be quite high in Yemen. There is no universal consensus on the treatment of this disease. The aim was to evaluate the efficacy and side effects of different therapeutic regimens used in patients of pemphigus in North-Western Yemen. Seventy-five Yemeni patients (39 males and 36 females) were included. Diagnosis was based on clinical features, histopathology and the Tzanck test. Results of treatment with these different therapeutic regimens were compared: (1) dexamethasone-cyclophosphamide pulse (DCP), (2) dexamethasone pulse with oral azathioprine, (3) oral prednisolone with azathioprine, (4) oral prednisolone with oral cyclophosphamide, and (5) prednisolone monotherapy. Pemphigus vulgaris (PV) was diagnosed in 46 patients, pemphigus foliaceus (PF) in 23, pemphigus vegetans (PVEG) in 5 and pemphigus herpetiformis (PH) in one. Among the 16 patients who received regular DCP therapy, 13 were in remission for 6 months to 11 years without medications (phase 4). Remission without pharmacotherapy could not be achieved with the other regimens and steroid-induced side-effects appeared to be more than with DCP. Immunofluorescence was not available to confirm the diagnosis of pemphigus. Randomization was not done. The DCP regimen seemed to be superior to the other regimens used.

  11. Hyperbaric oxygen therapy for pyoderma gangrenosum associated with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Hyun Il Seo

    2018-01-01

    Full Text Available Pyoderma gangrenosum (PG, an ulcerating skin condition, is rare in patients with ulcerative colitis (UC. We report a case of successful treatment of PG in a patient with UC using hyperbaric oxygen therapy (HBOT. The patient had UC that was in remission following treatment with mesalazine and azathioprine therapy. After visiting an orthopedic clinic, the patient opted for treatment with antibiotics and daily dressing of the ulcerative skin lesions, while azathioprine was discontinued. However, the lesions did not improve. Two months later, the patient visited a dermatologist who diagnosed the lesions as PG, and he was admitted to our unit. Surgical debridement and HBOT were performed by a plastic surgeon in the emergency department. After 3 months of HBOT and topical treatment, the patient's PG completely resolved. His UC was still in remission with mesalazine alone. HBOT may be an effective and safe alternative treatment for PG associated with UC, particularly in patients in whom anti-tumor necrosis factor agents are unnecessary.

  12. Recognising and Managing Refractory Coeliac Disease: A Tertiary Centre Experience

    Science.gov (United States)

    Nasr, Ikram; Nasr, Iman; Beyers, Carl; Chang, Fuju; Donnelly, Suzanne; Ciclitira, Paul J.

    2015-01-01

    Refractory coeliac disease (RCD) is a rare complication of coeliac disease (CD) and involves malabsorption and villous atrophy despite adherence to a strict gluten-free diet (GFD) for at least 12 months in the absence of another cause. RCD is classified based on the T-cells in the intra-epithelial lymphocyte (IEL) morphology into type 1 with normal IEL and type 2 with aberrant IEL (clonal) by PCR (polymerase chain reaction) for T cell receptors (TCR) at the β/γ loci. RCD type 1 is managed with strict nutritional and pharmacological management. RCD type 2 can be complicated by ulcerative jejunitis or enteropathy associated lymphoma (EATL), the latter having a five-year mortality of 50%. Management options for RCD type 2 and response to treatment differs across centres and there have been debates over the best treatment option. Treatment options that have been used include azathioprine and steroids, methotrexate, cyclosporine, campath (an anti CD-52 monoclonal antibody), and cladribine or fluadribine with or without autologous stem cell transplantation. We present a tertiary centre’s experience in the treatment of RCD type 2 where treatment with prednisolone and azathioprine was used, and our results show good response with histological recovery in 56.6% of treated individuals. PMID:26633478

  13. Recurrent Iliofemoral Venous Thrombosis in the Setting of May-Thurner Syndrome as the Presenting Symptom of Behcet's Disease.

    Science.gov (United States)

    Lakha, Sameer; Png, Chien Yi Maximilian; Chun, Kevin; Ting, Windsor

    2018-02-23

    Vascular manifestations including pulmonary artery aneurysms and venous thrombosis are seen in up to 14% of patients with Behcet's disease. We report a patient who had recurrent deep vein thrombosis (DVT) as the presenting symptom of Behcet's Disease. A 19-year-old male who presented with acute iliofemoral DVT, confirmed by intravascular ultrasound (IVUS) and venogram. May-Thurner syndrome was also observed. Repeated catheter-based pharmacomechanical thrombolysis, thrombectomy, and subsequent iliac vein stenting were performed. The patient was then discharged on rivaroxaban and aspirin. Five months later, the patient experienced left calf pain. In the interim, he had been diagnosed with Behcet's disease by a rheumatologist who was consulted due to oral ulcers and skin lesions and accordingly started on prednisone, colchicine, and azathioprine. At this time, IVUS and venogram revealed thrombotic occlusion of the previously placed stent. Tissue plasminogen activator was infused into the stent, and pharmacomechanical thrombectomy restored flow through the left iliac veins. Follow-up laboratory workup revealed that subtherapeutic azathioprine dosing, and after appropriate adjustment, the patient has been asymptomatic for 12 months. Acute refractory DVT is a possible presenting symptom of Behcet's disease, which may be complicated by May-Thurner syndrome. Such patients should receive therapeutic immunosuppression in addition to anticoagulation. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    International Nuclear Information System (INIS)

    Pennock, J.L.; Reitz, B.A.; Beiber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-01-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either Cy A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy

  15. Recognising and Managing Refractory Coeliac Disease: A Tertiary Centre Experience

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    Ikram Nasr

    2015-12-01

    Full Text Available Refractory coeliac disease (RCD is a rare complication of coeliac disease (CD and involves malabsorption and villous atrophy despite adherence to a strict gluten-free diet (GFD for at least 12 months in the absence of another cause. RCD is classified based on the T-cells in the intra-epithelial lymphocyte (IEL morphology into type 1 with normal IEL and type 2 with aberrant IEL (clonal by PCR (polymerase chain reaction for T cell receptors (TCR at the β/γ loci. RCD type 1 is managed with strict nutritional and pharmacological management. RCD type 2 can be complicated by ulcerative jejunitis or enteropathy associated lymphoma (EATL, the latter having a five-year mortality of 50%. Management options for RCD type 2 and response to treatment differs across centres and there have been debates over the best treatment option. Treatment options that have been used include azathioprine and steroids, methotrexate, cyclosporine, campath (an anti CD-52 monoclonal antibody, and cladribine or fluadribine with or without autologous stem cell transplantation. We present a tertiary centre’s experience in the treatment of RCD type 2 where treatment with prednisolone and azathioprine was used, and our results show good response with histological recovery in 56.6% of treated individuals.

  16. Non-paraneoplastic Lambert-Eaton myasthenic syndrome: a brief review of 10 cases

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    Paulo J. Lorenzoni

    2010-12-01

    Full Text Available Lambert-Eaton myasthenic syndrome (LEMS is an immune-mediated disorder of the presynaptic neuromuscular transmission, which more frequently occurs as the remote effect of a neoplasm, in the paraneoplastic form (P-LEMS, or in a non-paraneoplastic form (NP-LEMS; but few studies describe the clinical features of NP-LEMS. We analyzed the clinical manifestations, laboratory findings, electrophysiological studies, and treatment responses in ten Brazilian patients suffering from NP-LEMS. The mean age was 41.5 years. More often neurological findings were hyporeflexia or areflexia with a post-exercise improvement. Treatment response occurred with pyridostigmine, guanidine, prednisone, azathioprine, and cyclosporine; but not response was observed after intravenous immunoglobulin and plasma exchange. Age at onset, clinical manifestations, and electrophysiological abnormalities can help more in the diagnosis than serum antibodies; the symptomatic treatment with pyridostigmine was effective; and the immunosuppressive treatment with prednisone, azathioprine, or cyclosporine was more beneficial than plasma exchange or intravenous immunoglobulin treatment.

  17. Perspective on future therapy of vasculitis.

    Science.gov (United States)

    Boumpas, D T; Kritikos, H D; Daskalakis, N G

    2000-10-01

    This article summarizes recent advances in the management of various vasculitic syndromes and discusses potential new therapies based on a better understanding of their pathogenesis and natural history. Current efforts for optimization of testing for antineutrophil cytoplasmic antibodies and improvement of diagnostic criteria will certainly have a significant impact on future therapy. Biologic agents such as interferon-alpha are already in use in various vasculitides, whereas others, such as inhibitors of tumor necrosis factor-alpha, are in phase I clinical trials. Agents that selectively inhibit distinct steps in the pathogenesis of vasculitis are in preclinical or early clinical stages of development. Newer (mycophenolate mofetil, leflunamide) or older (methotrexate, azathioprine) immunosuppresive agents are finding new roles in the management of vasculitides. For patients with severe vasculitis, short-term use of cytotoxic agents, such as cyclophosphamide, alone or in combination with biologic agents, may expedite remission, which could then be better maintained with other, less toxic (and less expensive) immunosuppressive agents, such as methotrexate, azathioprine, mycophenolate mofetil, and leflunamide. For patients with mild or moderately severe vasculitis, these latter agents alone may be adequate. New therapeutic studies in vasculitis should better address the impact of therapy on health-related quality of life and its long-term toxicity.

  18. Spectroscopic investigations (FT-IR & FT-Raman) and molecular docking analysis of 6-[1-methyl-4-nitro-1H-imidazol-5-yl) sulfonyl]-7H-purine

    Science.gov (United States)

    Prasath, M.; Govindammal, M.; Sathya, B.

    2017-10-01

    The Azathioprine is used as anticancer agent. Azathioprine is chemically called 6-[1-methyl-4-nitro-1H-imidazol-5-yl) sulfonyl]-7H-purine (6M4N5P). The vibrational analysis of the 6M4N5P compound was carried out by using FT-IR and FT-Raman spectroscopic techniques and compared with aspects. The optimized geometry, frequency and intensity of the vibrational bands of 6M4N5P were obtained from the HF and DFT methods with 6-31G (d,p) basis set. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. The calculated Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energies show that charge transfer occur within the molecule. MEP (Molecular Electrostatic Potential) is very useful in the investigation of the charge distributions and molecular structure. The molecule orbital contributions were determined by using the total density of states (TDOS). A molecular docking analysis has been carried out to understand the conformational change and electrostatic properties of 6M4N5P in the active site of Rac1-Receptor.

  19. Remission Achieved in Refractory Advanced Takayasu Arteritis Using Rituximab

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    D. Ernst

    2012-01-01

    Full Text Available A 25-year-old patient was referred due to subclavian stenosis, identified on echocardiography. She presented with exertional dizziness and dyspnoea. Questioning revealed bilateral arm claudication. Examination demonstrated an absent right ulnar pulse and asymmetrical brachial blood pressure. Bruits were evident over both common carotid arteries. Doppler ultrasound and MRI angiograms revealed occlusion or stenosis in multiple large arteries. Takayasu arteritis (TA was diagnosed and induction therapy commenced: 1 mg/kg oral prednisolone and 500 mg/m2 intravenous cyclophosphamide (CYC. Attempts to reduce prednisolone below 15 mg/d proved impossible due to recurring disease activity. Adjuvant azathioprine 100 mg/d was subsequently added. Several weeks later, the patient was admitted with a left homonymous hemianopia. The culprit lesion in the right carotid artery was surgically managed and the patient discharged on azathioprine 150 mg/d and prednisolone 30 mg/d. Despite this, deteriorating exertional dyspnoea and angina pectoris were reported. Reimaging confirmed new stenosis in the right pulmonary artery. Surgical treatment proved infeasible. Given evidence of refractory disease activity on maximal standard therapy, we initiated rituximab, based on recently reported B-cell activity in TA.

  20. Successful Treatment of Small Intestinal Bleeding in a Crohn’s Patient with Noncirrhotic Portal Hypertension by Transjugular Portosystemic Shunt Placement and Infliximab Treatment

    Directory of Open Access Journals (Sweden)

    Benjamin Heimgartner

    2016-10-01

    Full Text Available Small intestinal bleeding in Crohn’s disease patients with noncirrhotic portal hypertension and partial portal and superior mesenteric vein thrombosis is a life-threatening event. Here, a case is reported in which treatment with azathioprine may have resulted in nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis. The 56-year-old patient with Crohn’s disease developed nodular regenerative hyperplasia under treatment with azathioprine. He was admitted with severe bleeding. Gastroscopy showed small esophageal varices without bleeding stigmata. Blood was detected in the terminal ileum. CT scan revealed a partial portal vein thrombosis with extension to the superior mesenteric vein, thickening of the jejunal wall and splenomegaly. Because intestinal bleeding could not be controlled by conservative treatment, the thrombus was aspirated and a transjugular intrahepatic portosystemic shunt (TIPS was placed. Switching the immunosuppressive medication to infliximab controlled Crohn’s disease activity. Bleeding was stopped, hemoglobin normalized, and thrombocytopenia and bowel movements improved. In summary, small intestinal bleeding in a Crohn’s patient with nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis can be efficiently treated by TIPS. TIPS placement together with infliximab treatment led to the improvement of the blood panel and remission in this patient.

  1. Gastrointestinal system manifestations in juvenile systemic lupus erythematosus.

    Science.gov (United States)

    Sönmez, Hafize Emine; Karhan, Asuman Nur; Batu, Ezgi Deniz; Bilginer, Yelda; Gümüş, Ersin; Demir, Hülya; Yüce, Aysel; Özen, Seza

    2017-07-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68.4%). The GIS manifestations due to SLE were autoimmune hepatitis (AIH) (n = 8) and lupus enteritis (n = 1). Manifestations associated with SLE were hepatomegaly and hypertransaminasemia due to macrophage activation syndrome (MAS) (n = 3) and hepatic steatosis (n = 1). GIS manifestations as a result of the adverse events of drugs were as follows: toxic hepatitis (n = 3; associated with methotrexate and nonsteroidal anti-inflammatory drugs in one, methotrexate in another, and azathioprine in another patient), azathioprine-induced cholestatic hepatitis (n = 1), and gastritis associated with corticosteroid (n = 1). In one patient, acute appendicitis occurred as a coincidence. In this study, one of every five pediatric SLE patients had GIS-related manifestations. GIS involvement may occur as an initial manifestation of the disease.

  2. Lupus nephritis. Remissions and relapses. Long-term follow up of 84 patients

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    Gerardo Oscar Mogni

    2014-06-01

    Full Text Available Introduction: Nephritis is the most common of all serious manifestations of SLE. The proliferative forms require immunosuppressive treatment, but responses are not consistent and exacerbations are frequent during or after the treatment has been completed. Methods: We retrospectively analyzed the evolution of a cohort of 84 patients with proliferative lupus nephritis with immunosuppressive treatment, in a long-term (up to 203 months follow up. Were taken as basal: sex, age, latency between onset and diagnosis of SLE nephritis, serum complement, plasmatic creatinine and proteinuria. We evaluated: initial response to therapy, occurrence of relapse or recurrence and score at the end of the observation period. Results: Remission of initial nephritis was seen in 73% of the cases, although at the end of monitoring only 54% of patients were in remission. 45 patients had one episode of nephritis, 32 patients had two, and 7 patients had three. Most of the remissions took place during the maintenance period. Complete remission had better evolution than partial remission. High serum creatinine levels and proteinuria at baseline were indicators of bad prognosis. Oral Azathioprine was more effective than quarterly IV Cylophosphamide as maintenance therapy, despite of a high incidence of relapses. Mycophenolate was not more effective than Cyclophosphamide/azathioprine for the treatment of relapses or recurrences. Conclusions: Our results are similar to the literature. Extended follow up enables the evaluation of the long term result of the initial symptoms, any possible future outbreaks, the effectiveness of the treatment and its evolution after its interruption.

  3. Myasthenia gravis: an update for the clinician.

    Science.gov (United States)

    Sieb, J P

    2014-03-01

    This paper provides a thorough overview of the current advances in diagnosis and therapy of myasthenia gravis (MG). Nowadays the term 'myasthenia gravis' includes heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular transmission as the common feature. Myasthenia gravis should be classified according to the antibody specificity [acetylcholine, muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at onset (in children; aged less than or more than 50 years) and type of course (ocular or generalized). With optimal treatment, the prognosis is good in terms of daily functions, quality of life and survival. Symptomatic treatment with acetylcholine esterase inhibition is usually combined with immunosuppression. Azathioprine still remains the first choice for long-term immunosuppressive therapy. Alternative immunosuppressive options to azathioprine include cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging therapy options include belimumab, eculizumab and the granulocyte- macrophage colony-stimulating factor. One pilot study on etanercept has given disappointing results. For decades, thymectomy has been performed in younger adults to improve non-paraneoplastic MG. However, controlled prospective studies on the suspected benefit of this surgical procedure are still lacking. In acute exacerbations, including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and immunoadsorption are similarly effective. © 2013 British Society for Immunology.

  4. [Skeletal changes in the kidney transplant patient].

    Science.gov (United States)

    Orzincolo, C; Bagni, B; Bedani, P L; Ghedini, M; Scutellari, P N

    1994-06-01

    The skeletal status was investigated with noninvasive diagnostic procedures in 44 renal transplant patients (mean time since intervention: 5 to 195 months) treated with steroid and azathioprine (21 cases) or with steroid, azathioprine and cyclosporine (23 cases). 38.6% of the patients had reduced renal function (creatininemia: 1.6-3.0 mg/dl). Our patients underwent biochemical and hormonal tests of bone metabolism, digital radiographs of the skeleton and bone mineral density measurement with dual-energy X-ray absorptiometry (DXA, Hologic QDR 1000). All the patients exhibited moderate to severe osteopenia at both radiographic and densitometric investigations; the risk of fracture was high in 47% of cases. Radiographic signs of vertebral fractures were observed in 4.5% of cases. Other major radiographic patterns were the aseptic necrosis of femoral head (9%), of carpal bone (4.5%) and of humeral head (2.2%). Fibrous osteitis was demonstrated in three patients. Geodes in the wrist were also observed. The correlation of bone densitometry values and time since renal transplantation was statistically significant (r = 0.381; p < 0.01). Moreover, the grade of osteopenia correlated with serum levels of calcitonin and calcitriol--the latter especially in the patients with severe osteopenia.

  5. Gastrointestinal disorders after immunosuppression: an experimental model to evaluate the influence of monotherapy on motility parameters.

    Science.gov (United States)

    Dall'Agnol, Denize Jussara Rupolo; Corá, Luciana Aparecida; Teixeira, Maria do Carmo Borges; de Lima, Maysa Bruno; Gama, Loyane Almeida; Miranda, José Ricardo de Arruda; Américo, Madileine Francely

    2017-08-01

    What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Male Wistar rats were randomly distributed into the following treatment groups: ciclosporin, tacrolimus, prednisone, sirolimus, mycophenolate mofetil, everolimus, azathioprine and control. Each animal was treated for 14 days by gavage with dosages ranging from 1 to 20 mg kg -1  day -1 considering the area-to-volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by alternating current biosusceptometry before and after treatment. Gastric emptying was faster in animals treated with tacrolimus, prednisone, sirolimus and everolimus compared with control animals (126.7 ± 12.7 min). There was a significant increase in the frequency of contractions after ciclosporin, tacrolimus, azathioprine and sirolimus treatment compared with control animals (4.6 ± 0.3 cycles min -1 ). Increases in the amplitude of contraction were observed after treatment with tacrolimus, sirolimus and everolimus compared with control rats (34.9 ± 6.0 dB). The results showed that our animal model was suitable for demonstrating that most immunosuppressive drugs

  6. Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease.

    Science.gov (United States)

    Watanabe, Kenji; Matsumoto, Takayuki; Hisamatsu, Tadakazu; Nakase, Hiroshi; Motoya, Satoshi; Yoshimura, Naoki; Ishida, Tetsuya; Kato, Shingo; Nakagawa, Tomoo; Esaki, Motohiro; Nagahori, Masakazu; Matsui, Toshiyuki; Naito, Yuji; Kanai, Takanori; Suzuki, Yasuo; Nojima, Masanori; Watanabe, Mamoru; Hibi, Toshifumi

    2017-11-11

    We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. We compared simple endoscopic scores for CD in between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04-4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77-2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72-0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84-0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14-1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001). In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at

  7. Systemic lupus erythematosus in Thai children: clinicopathologic findings and outcome in 82 patients.

    Science.gov (United States)

    Pattaragarn, Anirut; Sumboonnanonda, Achra; Parichatikanond, Paisal; Supavekin, Suroj; Suntornpoch, Vibul; Vongjirad, Arun

    2005-11-01

    To define the patterns of clinicopathologic findings and to identify the risk factors for renal failure and mortality of childhood-onset systemic lupus erythematosus (SLE) in Thailand. The study is a retrospective analysis of clinical manifestations, laboratory data, and pathologic findings, treatment modalities, and outcome of 82 patients with biopsy-proven lupus nephritis (LN) with disease onset between I January 1987 and 31 December 1997. All children developed these first manifestations at the age 13 years or under Sixty-four (789%) patients were females and eighteen (22%) were males (ratio female/male = 3.5:1). The patients were followed for a mean period of 53.6 months (range 1 -141). The mean age at disease onset was 9.2 years (range 2-12.6). Class-IV LN, observed in 40 (48.8%) patients, was the most frequent histopathology on initial renal biopsy. Less frequent findings were class-II (30.5%), V (14.6%), I (3.7%) and III (2.4%) LN. Based on the renal histopathology and clinical presentations, patients were treated with corticosteroids alone or in combination with azathioprine or with intravenous cyclophosphamide (CYC). Methylprednisolone pulses were given in patients with clinically more severe disease. Follow-up biopsies, performed in 12 patients, showed no change in 4 patients, and were progressive in 8 patients. On final clinical evaluation, 20 patients died, 65% died from serious infections, 15% from cardiopulmonary complications, and 10% from end stage renal disease. As the whole group, survival rates were 89% and 74% at 12 and 60 months, respectively. The 5-year patient survival in class-II, class-IV and class- VLN patients were 83%, 67% and 64%, respectively. Within the group of class-IV LN, the 5-year survival in the patients treated with intravenous CYC was significantly better than those receiving prednisolone with or without azathioprine. Five-year kidney survival rates from the time of diagnosis to the endpoints of terminal renal failure were 94

  8. Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

    Science.gov (United States)

    Sánchez, Elena; García de la Torre, Ignacio; Sacnún, Mónica; Goñi, Mario; Berbotto, Guillermo; Paira, Sergio; Musuruana, Jorge Luis; Graf, César; Alvarellos, Alejandro; Messina, Osvaldo D; Babini, Alejandra; Strusberg, Ingrid; Marcos, Juan Carlos; Scherbarth, Hugo; Spindler, Alberto; Quinteros, Ana; Toloza, Sergio; Moreno, José Luis C; Catoggio, Luis J; Tate, Guillermo; Eimon, Alicia; Citera, Gustavo; Pellet, Antonio Catalán; Nasswetter, Gustavo; Cardiel, Mario H; Miranda, Pedro; Ballesteros, Francisco; Esquivel-Valerio, Jorge A; Maradiaga-Ceceña, Marco A; Acevedo-Vásquez, Eduardo M; García, Conrado García; Tusié-Luna, Teresa; Pons-Estel, Bernardo A; Alarcón-Riquelme, Marta E

    2017-12-01

    To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (p Bonferroni ancestry correlated with higher doses of azathioprine (p ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

  9. Marfan syndrome with antineutrophil cytoplasmic antibody-associated systemic vasculitis presenting as severe anaemia and haematuria after the Bentall procedure.

    Science.gov (United States)

    Sijia, Li; Shuangxin, Liu; Wei, Shi; Yanhai, Cui

    2013-08-01

    One month previously, a 28-year old male underwent an emergency modified Bentall procedure because of Marfan syndrome with acute aortic dissection Stanford Class A. Computed tomography of the chest did not reveal severe graft stenosis of the anastomosis. To explore the cause of anaemia, renal dysfunction and macroscopic haematuria, the patient was tested for antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (AASV). Antimyeloperoxidase antibodies (MPO)-ANCA and antiproteinase 3 antibodies (PR3)-ANCA were strongly positive. Corticosteroid therapy was applied, followed by cyclophosphamide and azathioprine. In response to treatment, the MPO-ANCA and PR3-ANCA levels gradually decreased, proteinuria was alleviated and haemoglobin levels returned to normal after 6 months. This is the first report to highlight haemolytic anaemia and AASV with Marfan syndrome after surgery for aortic dissection.

  10. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Sarma Nilendu

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

  11. Management of pemphigus vulgaris: challenges and solutions

    Science.gov (United States)

    Gregoriou, Stamatis; Efthymiou, Ourania; Stefanaki, Christina; Rigopoulos, Dimitris

    2015-01-01

    The main objective in the treatment of pemphigus vulgaris is to control the disease, prevent relapses, and avoid adverse events associated with the prolonged use of steroids and immunosuppressive agents. Systemic corticosteroids remain the gold standard treatment for pemphigus vulgaris. Azathioprine and mycophenolate mofetil are the first line of steroid-sparing treatment. Rituximab is extremely effective in recalcitrant pemphigus, when other treatments fail to control the disease. The European Dermatology Forum recommends tapering prednisolone by 25% every 2 weeks after the consolidation phase, and a 5 mg reduction every 4 weeks when the dose is reduced to <20 mg. If the patient relapses, options include increasing steroids back to the previous dose, adding an immunosuppressant if using steroid monotherapy, or replacing a first-line immunosuppressant by another if already on combination therapy. PMID:26543381

  12. Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: Report of two cases

    Directory of Open Access Journals (Sweden)

    Reddy I

    2005-01-01

    Full Text Available Disseminated strongyloidiasis is a rare manifestation in patients on immunosuppressive drugs. We report two cases of fatal disseminated Strongyloides stercoralis infestation. The first was in a patient of pemphigus vulgaris who developed an exacerbation of symptoms, one year after diagnosis and was given intravenous dexamethasone and azathioprine and in the third week of hospitalization developed features of septicemia, respiratory failure and petechial hemorrhages which were proven to be due to disseminated strongyloidiasis. The second patient was diagnosed to have stage IV diffuse large cell type of non-Hodgkin lymphoma and after the second cycle of chemotherapy, developed generalized symptoms of septicemia, respiratory failure, purpuric macules and patches. This was also proven to be disseminated strongyloidiasis.

  13. Mycophenolate mofetil in autoimmune and inflammatory skin disorders.

    Science.gov (United States)

    Nousari, H C; Sragovich, A; Kimyai-Asadi, A; Orlinsky, D; Anhalt, G J

    1999-02-01

    Mycophenolate mofetil (MMF) has been widely used as an immunosuppressant in organ transplantation. MMF has recently been added to therapeutic regimens for skin disorders. Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin diseases, including 4 cases of pemphigus vulgaris, 1 case of pemphigus foliaceus, 1 case of perineal and metastatic cutaneous Crohn's disease, 1 case of bullous pemphigoid and psoriasis, and 1 case of psoriasis. Most of these patients had refractory disease or had developed significant side effects to conventional therapy, including azathioprine, methotrexate, prednisone, cyclosporine, acitretin, PUVA, UVB, and tacrolimus. MMF was effective and well tolerated in all these patients. The dosages of MMF ranged from 500 mg twice daily (for psoriasis and Crohn's disease) to 1250mg twice daily (for 3 of 4 patients with pemphigus vulgaris). MMF is an effective and relatively safe immunosuppressant in autoimmune and inflammatory skin diseases.

  14. Retroperitoneal fibrosis - a report of five cases.

    Science.gov (United States)

    Runowska, Marta; Majewski, Dominik; Puszczewicz, Mariusz

    2017-01-01

    Retroperitoneal fibrosis (RPF) is a rare disease, characterized by inflammation and deposition of fibrotic tissue in the vicinity of the abdominal aorta and iliac arteries. We present a report of five patients admitted to our department between January 2014 and February 2017, diagnosed with RPF. Abdominal pain was the most common presenting symptom; however, in one patient, RPF was identified accidentally in routinely performed ultrasonography. In 4 cases, corticosteroids (CS) in combination with azathioprine were applied as first-line therapy, whereas one patient was treated with intravenous methylprednisolone pulses followed by oral CS. In this paper, clinical features as well as laboratory and radiographic findings together with management and treatment outcomes in patients with RPF are discussed. Given the rarity of the condition, it seems important to report every single case of RPF to help establish its management algorithm.

  15. Generalized subcutaneous edema as a rare manifestation of dermatomyositis: clinical lesson from a rare feature.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-04-01

    Generalized subcutaneous edema is a very rare manifestation of inflammatory myopathies. A 61-year-old woman presented with classic signs and symptoms of dermatomyositis. She was also noted to have generalized edema that was so florid that an alternative diagnosis was considered. Her disease was resistant to corticosteroids, azathioprine, and mycophenolate mofetil. Intravenous administration of immunoglobulins was started because of marked worsening of her disease-muscle weakness, generalized anasarca, and involvement of her bulbar muscles. This led to dramatic resolution of her subcutaneous edema and significant improvement of her skin and muscle disease. As the initial screen for malignancy was negative, a positron emission tomography-computed tomography scan was requested, which interestingly showed a metabolically active cervical tumor. Anasarca is an unusual manifestation of dermatomyositis. In treatment-refractory cases, it seems reasonable to consider positron emission tomography scan in excluding underlying malignant disease.

  16. Current status of lupus nephritis

    Science.gov (United States)

    Jaryal, Ajay; Vikrant, Sanjay

    2017-01-01

    Systemic lupus erythematosus (SLE) is a systemic disease of unknown aetiology with variable course and prognosis. Lupus nephritis (LN) is one of the important disease manifestations of SLE with considerable influence on patient outcomes. Immunosuppression therapy has made it possible to control the disease with improved life expectancy and quality of life. In the last few decades, various studies across the globe have clarified the role, dose and duration of immunosuppression currently in use and also provided evidence for new agents such as mycophenolate mofetil, calcineurin inhibitors and rituximab. However, there is still a need to develop new and specific therapy with less adverse effects. In this review, the current evidence of the treatment of LN and its evolution, and new classification criteria for SLE have been discussed. Also, rationale for low-dose intravenous cyclophosphamide as induction agent followed by azathioprine as maintenance agent has been provided with emphasis on individualized and holistic approach. PMID:28639592

  17. Successful treatment of idiopathic pulmonary capillaritis with intravenous cyclophosphamide.

    LENUS (Irish Health Repository)

    Flanagan, Frances

    2013-03-01

    Idiopathic pulmonary hemosiderosis (IPH), a subtype of diffuse alveolar hemorrhage is a rare condition, first described by Virchow in 1864. Historically, it manifests in children in the first decade of life with the combination of hemoptysis, iron deficiency anemia, and alveolar infiltrates on chest radiograph. More recently, diffuse alveolar hemorrhage has been classified by the absence or presence of pulmonary capillaritis (PC), the latter carrying a potential for a poorer outcome. While systemic corticosteroids remain the first line treatment option, other immune modulators have been trailed including hydroxychloroquine, azathioprine, 6-mercaptopurine, and cyclophosphamide with varying results. Our case demonstrates for the first time, the successful use of intravenous cyclophosphamide in the management of chronic idiopathic PC.

  18. Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita.

    Science.gov (United States)

    Kofler, H; Wambacher-Gasser, B; Topar, G; Weinlich, G; Schuler, G; Hintner, H; Romani, N; Fritsch, P

    1997-02-01

    Epidermolysis bullosa acquisita is an uncommon autoimmune bullous disease of the skin and mucous membranes. It is chronic, disabling, and difficult to treat. We describe a case of severe epidermolysis bullosa acquisita of 7 years' duration that had been treated with azathioprine, corticosteroids, chlorambucil, plasma exchanges, cyclophosphamide, cyclosporine, and colchicine without any lasting effect. Seven cycles of treatment were administered with immunoglobulin given intravenously at a low dose, 40 mg/kg body weight daily for 5 days. The patient was free of disease for 10 months after the initiation of therapy. We suggest that low-dose regimens of immunoglobulins may be as effective in this disease as the high-dose regimens suggested in the literature, and at much lower cost.

  19. Infliximab-induced intertriginous psoriasis in patient with Crohn's desease

    Directory of Open Access Journals (Sweden)

    Federica Mola

    2011-10-01

    Full Text Available Tumor necrosis factor-α (TNFα inhibition is an effective treatment of moderate-to-severe psoriasis and other diseases (rheumatoid arthritis, ankylosing spondylitis, psoriasis or Crohn’s disease. We report a case of a 32- years-old patient affected by Crohn’s disease since the age of 25 who started infliximab infusion after four years of treatment with prednisone and azathioprine per os without improvement. After the fifth infusion of infliximab, he developed a form of intertriginous psoriasis which was approached with topical steroid cream. The patient never presented psoriasis in the past. New onset of psoriasis in patients without history for skin diseases (as in our case is a quite uncommon complication of TNFα inhibitor therapy. The increased production of IFNα during TNFα inhibitor therapy is a possible pathophysiologic explanation for this paradoxical effect of the anti-TNFα.

  20. Pharmacogenomics Implementation at the National Institutes of Health Clinical Center.

    Science.gov (United States)

    Sissung, Tristan M; McKeeby, Jon W; Patel, Jharana; Lertora, Juan J; Kumar, Parag; Flegel, Willy A; Adams, Sharon D; Eckes, Ellen J; Mickey, Frank; Plona, Teri M; Mellot, Stephanie D; Baugher, Ryan N; Wu, Xiaolin; Soppet, Daniel R; Barcus, Mary E; Datta, Vivekananda; Pike, Kristen M; DiPatrizio, Gary; Figg, William D; Goldspiel, Barry R

    2017-10-01

    The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol. In the second phase, we implemented genotyping for drug-metabolizing enzymes and transporters: SLCO1B1 for CDS of simvastatin and TPMT for CDS of mercaptopurine, azathioprine, and thioguanine. The purpose of this review is to describe the implementation process, which involves clinical, laboratory, informatics, and policy decisions pertinent to the NIH CC. © 2017, The American College of Clinical Pharmacology.

  1. Hodgkin's Lymphoma in Crohn's Disease Treated with Infliximab

    Directory of Open Access Journals (Sweden)

    Diana Carvalho

    2017-09-01

    Full Text Available Introduction: Lymphoproliferative disorders, particularly non-Hodgkin's and Hodgkin's lymphomas, are rare in patients with inflammatory bowel diseases. The use of thiopurines and infection by Epstein-Barr virus are well-known cofactors that can raise its prevalence. Other risk factors such as disease activity and biological treatment are the subject of discussion, without enough data in the literature to confirm a potential association. Methods: We report a case of Hodgkin's lymphoma in a patient who had been treated with azathioprine and was on long-term monotherapy with infliximab. Conclusions: We stress the importance of recognizing the possible occurrence of a lymphoproliferative disorder in association with anti-tumor necrosis factor-α therapy

  2. Diagnosis and treatment of fistulising Crohn's disease

    DEFF Research Database (Denmark)

    Hvas, Christian Lodberg; Dahlerup, Jens Frederik; Jacobsen, Bent Ascanius

    2011-01-01

    /MRI for complete anatomical definition. Any abscess should be drained, and the disease extent throughout the entire gastrointestinal tract should be evaluated. Treatment goals for perianal fistulas include reduced fistula secretion or none, evaluated by clinical examination; the absence of abscesses; and patient......A fistula is defined as a pathological connection between the intestine and an inner (bladder or other intestine) or outer (vagina or skin) epithelial surface. Fistulas are discovered in up to 25% of all Crohn's disease patients during long-term follow-up examinations. Most are perianal fistulas...... satisfaction. MR imaging is required to demonstrate definitive fistula closure. Fistulotomy is considered for simple perianal fistulas. In complex perianal fistulas, antibiotics and azathioprine or 6-mercaptopurine, which are often combined with a loose seton, constitute the first-line medical therapy...

  3. Genetic variants in microsomal epoxide hydrolase and N-acetyltransferase 2 in susceptibility of IBD in the Danish population

    DEFF Research Database (Denmark)

    Ernst, Anja; Andersen, Vibeke; Østergaard, Mette

    , or severity of disease measured either as need for surgery or azathioprine treatment. Smoking was found to be a risk factor of CD (OR=1.8(1.4; 2.3) Pfactor regarding UC (0.7 (0.5-0.9) P=0.02) which is in agreement with previous findings in other study...... induce or sustain an immune response. Changes in detoxification of substances that causes epithelial damage may confer susceptibility to IBD. Hence, polymorphic enzymes involved in the detoxification processes may be risk factors of IBD. Methods. The two biotransformation enzymes microsomal epoxide...... hydrolase and N-acetyltransferase 2 were genotyped using TaqMan based Real-Time PCR in 388 patients with Crohn's disease (CD), 565 patients with ulcerative colitis (UC) and 796 healthy Danish controls. Results. No association was found between low microsomal epoxide hydrolase activity or slow N...

  4. Successful induction of granulomatosis with polyangiitis with tacrolimus

    Directory of Open Access Journals (Sweden)

    R Ramachandran

    2015-01-01

    Full Text Available We report a 50-year-old female who presented with inflammatory arthritis, upper respiratory tract symptoms, and microscopic hematuria with nephrotic range proteinuria. Antineutrophil cytoplasmic antibodies (ANCA were detectable and kidney biopsy showed pauci-immune focal necrotizing crescentic glomerulonephritis. She was treated with pulse intravenous cyclophosphamide (CYC and prednisolone. Patient developed severe leucopenia after the first dose and subsequently had leucopenia to low dose CYC, mycophenolate mofetil and azathioprine were also tried. However, patient developed leukopenia with all the above agents. Initiation of tacrolimus (TAC was followed by dramatic response: Proteinuria decreased, serum albumin normalized and C-ANCA and anti-PR3 ANCA assays became negative. This is the first successful case of TAC as an induction agent in a patient with GPA (ANCA associated vasculitis with renal involvement.

  5. Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

    Science.gov (United States)

    Alba, Marco A; Flores-Suárez, Luis Felipe

    2016-01-01

    ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. A rare prenatal case with two de novo inversions and a translocation: 48, XX,t(9;12)(q32;p24.3), inv(11)(p15.1q25), inv(13)(q12.q22)

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, B.; Balaban, L.; Eldred, C. [Albany Medical College, Albany, NY (United States)] [and others

    1994-09-01

    Ultrasound examination of a para 1, gravida 2, 26 y.o. showed severe hydrocephalus and polyhydramnios. Amniocentesis was performed at 27 weeks. High resolution chromosome analysis revealed a karyotype with a 9;12 translocation, a pericentric inversion of chromosome 11, and a paracentric inversion of chromosome 13. Parental chromosome studies were normal. The mother was not on medication prior to her pregnancy and there was no known exposure to radiation. Delivery was at 34 weeks gestation. The phenotype consisted of micrognathia, low set ears, hypertelorism, and hydrodcephaly. Review of the literature revealed a single report with multiple de novo aberrations consisting of a 6;14 translocation and a deleted 7. This was diagnosed in the child of a woman with systemic lupus erythematous treated with azathioprine. These types of abnormalities have been known to be induced by chemical and radiation exposure. High resolution banding combined with molecular studies presently improve our ability to detect subtle structural aberrations.

  7. Flares of systemic lupus erythematosus during pregnancy and the puerperium: prevention, diagnosis and management.

    Science.gov (United States)

    Stojan, George; Baer, Alan N

    2012-07-01

    Systemic lupus erythematosus is a systemic autoimmune disease that primarily affects women in their reproductive age years. Pregnancy in systemic lupus erythematosus now has favorable outcomes for the majority of women. However, flares of disease activity, preeclampsia, fetal loss, intrauterine growth retardation and preterm birth are established risks of such pregnancies. Active lupus nephritis at the time of conception poses the greatest risk for disease flares and poor obstetric outcomes. Patients should delay conception until their lupus has been in remission for at least 6 months. In addition, certain lupus medications are potentially teratogenic and need to be stopped before conception. The signs and symptoms of a lupus flare may mimic those of normal pregnancy, impeding its recognition during pregnancy. Hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone and azathioprine are commonly used to treat lupus flares during pregnancy.

  8. Immunosuppression in pregnant women with systemic lupus erythematosus.

    Science.gov (United States)

    Ponticelli, Claudio; Moroni, Gabriella

    2015-05-01

    Most pregnancies are successful in women with systemic lupus erythematosus, particularly if the disease is quiescent and there are no signs of active nephritis. There is no major impact of immunosuppression on maternal outcome. However, high doses of cyclosporine and glucocorticoids are used which may favor development of hypertension or preeclampsia. Some immunosuppressive drugs may exert toxic effects on the fetus. Glucocorticoids may cause small birth weight, and azathioprine and calcineurin inhibitors may be associated with lower birth weight, gestational age and prematurity. Cyclophosphamide may cause fetal malformation when given in the first trimester. Mycophenolate and leflunomide are teratogenic drugs and should be withdrawn before conception in case of programmed pregnancy or should be rapidly discontinued in case of unexpected pregnancy. Option counseling for pregnancy and correct use of immunosuppressive drugs are prerequisites for a successful pregnancy in women with lupus.

  9. Mycobacterium avium-intracellulare cellulitis occurring with septic arthritis after joint injection: a case report

    Directory of Open Access Journals (Sweden)

    Murdoch David M

    2007-02-01

    Full Text Available Abstract Background Cellulitis caused by Mycobacterium avium-intracellulare has rarely been described. Mycobacterium avium-intracellulare is a rare cause of septic arthritis after intra-articular injection, though the causative role of injection is difficult to ascertain in such cases. Case presentation A 57-year-old with rheumatoid arthritis treated with prednisone and azathioprine developed bilateral painful degenerative shoulder arthritis. After corticosteroid injections into both acromioclavicular joints, he developed bilateral cellulitis centered over the injection sites. Skin biopsy showed non-caseating granulomas, and culture grew Mycobacterium avium-intracellulare. Joint aspiration also revealed Mycobacterium avium-intracellulare infection. Conclusion Although rare, skin and joint infections caused by Mycobacterium avium-intracellulare should be considered in any immunocompromised host, particularly after intra-articular injection. Stains for acid-fast bacilli may be negative in pathologic samples even in the presence of infection; cultures of tissue specimens should always be obtained.

  10. [Inflammatory bowel diseases: conservative therapy].

    Science.gov (United States)

    Bansky, G

    1991-07-01

    Recent advances in the medical treatment of the inflammatory bowel diseases are reviewed with emphasizes on controlled clinical trials. The newly developed mesalazine contains the active moiety of sulfasalazine, the 5-aminosalicylic acid. In ulcerative colitis mesalazine appears to be as efficacious as the time-honored sulfasalazine; it has however less adverse effects. Corticosteroids remain the most effective drugs in severe attacks of all forms of inflammatory bowel diseases. The immunosuppressive agents 6-mercoptopurine and azathioprine are useful second-line drugs in otherwise refractory Crohn's disease. The place of cyclosporin is at present uncertain. Metronidazole is the only efficient antibiotics in the treatment of Crohn's disease. The relative merits of various diets are discussed.

  11. Report of validation study of assessment of direct immunotoxicity in the rat

    DEFF Research Database (Denmark)

    Dayan, A. D.; Kuper, F.; Madsen, Charlotte Bernhard

    1998-01-01

    . For this purpose scientists in a number of laboratories in different countries agreed to do joint studies, first of azathioprine (AZA) and then of cyclosporin A (CYA), as potent immunosuppressive compounds. The general experimental procedures and the detailed techniques employed were selected to explore whether......The International Collaborative Immunotoxicity Study (ICICIS) was established in 1986 as a joint activity of the International Programme on Chemical Safety (a cooperative programme of the United Nations Environment Programme, the International Labour Office and the World Health Organization...... compartments of lymphoid tissues) would suffice to indicate ('flag') the occurrence of immunotoxicity due to a chemical, or whether specific tests of immune function would be required. When the second chemical, CYA, was studied, standardisation of the protocol for the test, and of all the investigations...

  12. Epidemiologic and therapeutic aspects of refractory coeliac disease - a systematic review

    DEFF Research Database (Denmark)

    Rowinski, Sara Anna; Christensen, Erik

    2016-01-01

    INTRODUCTION: Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and because RCD has a poor prognosis due to progress to enteropathy-associated T-cell lymphoma, the aim was to review...... the epidemiologic aspects and the therapeutic options for RCD. METHODS: A systematic literature search was performed in 18 databases, and 122 records were identified. Incidence, prevalence, treatment methods and their efficacy were evaluated. RESULTS: Among coeliac disease patients, the cumulative incidence of RCD...... is 1-4% per ten-year period and the prevalence is 0.31-0.38%. In the general population, the prevalence of RCD is 0.002%. Treatment of RCDI is azathioprine (effect 100%), mesalamine (effect 60%) or tioguanine (effect 83%). Treatment for RCDII is the antimetabolite cladribine (effect 81%) and autologous...

  13. Cytomegalovirus retinitis treated with valganciclovir in Wegener’s granulomatosis

    Directory of Open Access Journals (Sweden)

    Kabata Y

    2012-03-01

    Full Text Available Yoshiaki Kabata1, Genichiro Takahashi1, Hiroshi Tsuneoka21Department of Ophthalmology, Jikei University School of Medicine, Katsushika Medical Center, Katsushika, Tokyo, Japan; 2Department of Ophthalmology, Jikei University School of Medicine, Minato, Tokyo, JapanAbstract: A case of cytomegalovirus (CMV retinitis in a patient with Wegener’s granulomatosis treated with oral valganciclovir as maintenance therapy is reported. A 68-year-old male patient with anti-proteinase-3 ANCA-positive Wegener’s granulomatosis who was receiving immunosuppressive therapy with methylprednisolone, cyclophosphamide, and azathioprine developed CMV retinitis. The patient received intravenous ganciclovir as induction therapy and oral valganciclovir as maintenance therapy. The patient responded to treatment and showed no recurrence for 8 months. There were no serious adverse effects associated with oral valganciclovir. Oral valganciclovir is convenient and effective for the management of CMV retinitis in the patient with Wegener’s granulomatosis.Keywords: cytomegalovirus retinitis, Wegener’s granulomatosis, valganciclovir, ganciclovir, maintenance therapy

  14. Efficacy of prophylactic irradiation in altering renal allograft survival

    International Nuclear Information System (INIS)

    Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.

    1974-01-01

    Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids

  15. Renal-sparing strategies in cardiac transplantation

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Ross, Heather J

    2009-01-01

    PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...... of sirolimus or everolimus. However, studies that use very early CNI discontinuation have found an increased risk of allograft rejection, and this strategy requires further study before it can be routinely recommended. CNI discontinuation late after cardiac transplantation seems more effective than CNI...

  16. Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis.

    Science.gov (United States)

    Gallego-Pinazo, Roberto; Dolz-Marco, Rosa; Martínez-Castillo, Sebastián; Arévalo, J Fernando; Díaz-Llopis, Manuel

    2013-02-01

    Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

  17. General principles for the treatment of non-infectious uveitis.

    Science.gov (United States)

    Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto; García-Delpech, Salvador; Salom-Alonso, David

    2009-09-01

    Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to develop the role of corticosteroid-saving agents. These can be organized in four other steps: Cyclosporine and Methotrexate in a second one; Azathioprine, Mycophenolate Mofetil and Tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a theoretical last one with Cyclophosphamide and Chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non infectious posterior uveitis.

  18. Endolymphatic irradiation. A useful method for immunosuppression in renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Galvao, M.M.; Ianhez, L.E.; Sabbaga, E. (Sao Paulo Univ. (Brazil). Faculdade de Medicina)

    1982-02-01

    The authors analysed the clinical evolution and the result of renal transplantation some years after irradiation in 24 patients (group I) who received endolymphatic /sup 131/I as a pre-transplantation immunosuppresive measure. The control group (group II) consisted of 24 non-irradiated patients comparable to group I in age, sex, primary disease, type of donor and immunosuppressive therapy. Significant differences were observed between the two groups regarding such factors as incidence and reversibility of rejection crises in the first 60 post-transplantation days, loss of kidney due to rejection, and dosage of azathioprine. The authors conclude that this method, besides being harmless, has prolonged immunosuppressive action, its administration being advised for receptors of cadaver kidneys, mainly those who show positive cross-match against HLA antigens for painel.

  19. Clinical utility of labeled cells for detection of allograft rejection and myocardial infarction

    International Nuclear Information System (INIS)

    Fawwaz, R.A.

    1984-01-01

    The choice of a specific radiolabeled blood component for use in detection of allograft rejection depends on several factors including the immunosuppressive agents used, the type of organ allografted, and particularly the length of time the allograft resides in the host and the duration of rejection. To date, only the use of 111In-labeled platelets in renal allograft recipients immunosuppressed with azathioprine and corticosteroids has shown clinical promise in the detection of early allograft rejection. Radiolabeled blood components are unlikely to play a significant role in detection of myocardial infarction. The use of these agents for monitoring therapeutic interventions or as indicators of prognosis in patients with myocardial infarction continues to be investigated

  20. Asymptomatic giant coronary aneurysm in an adolescent with Behcet's syndrome

    Directory of Open Access Journals (Sweden)

    Kahn Philip J

    2012-01-01

    Full Text Available Abstract Objective Behcet's is an idiopathic multi-organ syndrome, which may have onset during childhood. Vascular involvement is uncommon, with rarely reported coronary aneurysm formation. We present a case report of a teenager girl who developed recalcitrant life-threatening Behcet's vasculitis, involving both small and large venous and arterial systems including a giant coronary aneurysm. Case report De-identified data were collected retrospectively in case report format. Although our sixteen year old female with Behcet's vasculitis had resolution of many arterial aneurysms, she had persistent venous thrombosis of large vessels, as well as persistent, giant arterial aneurysms requiring intra-arterial coiling of a lumbar artery and coronary bypass grafting despite intensive immunosuppression including glucocorticoids, cyclophosphamide, infliximab, methotrexate, azathioprine and intravenous immunoglobulin. Conclusions Vascular manifestations may be seen in Behcet's syndrome, including asymptomatic coronary aneurysm, which may be refractory to immunosuppression and ultimately require surgical intervention. Increased awareness is essential for prompt diagnosis and management.

  1. Memory in myasthenia gravis: neuropsychological tests of central cholinergic function before and after effective immunologic treatment.

    Science.gov (United States)

    Glennerster, A; Palace, J; Warburton, D; Oxbury, S; Newsom-Davis, J

    1996-04-01

    There are reports of central cholinergic deficits in myasthenia gravis (MG) describing impaired performance on a variety of tests of memory with varying benefits from plasmapheresis. We tested 11 patients with symptomatic MG at the start of a trial of immunosuppressive treatment (prednisolone plus azathioprine or placebo) and again when in remission. The tests included the Logical Memory and Design Reproduction parts of the Wechsler Memory Scale, the Rey Auditory Verbal Learning Test, Peterson-Peterson task, and an auditory vigilance task. Muscle strength improved significantly over the period of treatment, but overall performance on tests of memory or attention did not. These results fail to substantiate reports of functionally significant and reversible central deficits in myasthenia gravis.

  2. Predicting, treating and preventing postoperative recurrence of Crohn's disease: the state of the field.

    Science.gov (United States)

    Borowiec, Anna M; Fedorak, Richard N

    2011-03-01

    The majority of patients diagnosed with Crohn's disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn's disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn's disease recurrence.

  3. Predicting, Treating and Preventing Postoperative Recurrence of Crohn’s Disease: The State of the Field

    Directory of Open Access Journals (Sweden)

    Anna M Borowiec

    2011-01-01

    Full Text Available The majority of patients diagnosed with Crohn’s disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn’s disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn’s disease recurrence.

  4. Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth

    DEFF Research Database (Denmark)

    Stormly Hansen, Michael; Klefter, Oliver Niels; Julian, Hanne Olsen

    2017-01-01

    Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon......, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and Meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti...... by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous...

  5. Successful immune moderation treatment for progressive encephalomyelitis with rigidity and myoclonus.

    Science.gov (United States)

    Ueno, Shinichi; Miyamoto, Nobukazu; Shimura, Hideki; Ueno, Yuji; Watanabe, Masao; Hayashi, Akito; Hattori, Nobutaka; Urabe, Takao

    2015-01-01

    Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disease. PERM consists of the same symptoms as stiff person syndrome, in addition to sensory, brainstem and autonomic features. We herein report a case of PERM in a 48-year-old woman who initially presented with spasticity of the lower limbs and subsequently developed upper limb spasticity, perioral myoclonus and restlessness after three months. The onset of potentially fatal dysautonomia was observed at the peak of the disease. Treatment with high-dose immunoglobulin (400 mg/kg, 5 days), levetiracetam and azathioprine resulted in a drastic and sustained improvement of these symptoms. This is an interesting case of PERM in which the patient showed a dramatic improvement following immune moderation.

  6. [Lung epithelioid hemangioendothelioma: Report of one case].

    Science.gov (United States)

    Quiroz, Manuel; Undurraga, Álvaro; Moya, Rafael; Fernández, Cristina; Bezares, Katiuska; Linacre, Virginia

    2017-05-01

    Epithelioid hemangioendothelioma is a multifocal tumor that rarely metastasizes. It is difficult to diagnose, most often it is an incidental finding in young asymptomatic women. The radiologic pattern is heterogeneous. Histologic confirmation of Weibel-Palade bodies or immunohistochemistry based on specific tumor markers such as factor VIII and CD34 are the most important finding to confirm the diagnosis. We report a 21 years old woman Presenting with cough and dyspnea. A chest X ray was suggestive of tuberculosis. Sputum smears were negative for acid fat bacilli and the tuberculin test was negative. A chest CAT scan showed multiple nodular lesions. A surgical biopsy of the lesions confirmed the presence of a hemangioendothelioma. The patient was initially treated with prednisone and azathioprine without response. Thereafter, the patient is without treatment and without evidence of disease progression.

  7. Cryoglobulinemic vasculitis preceding diagnosis of Carney Complex

    DEFF Research Database (Denmark)

    Glerup, Mia; Stausbøl-Grøn, Brian; Heuck, Carsten

    2014-01-01

    Carney complex (CNC) is a disorder characterized by skin pigmentary abnormalities and benign cardiac, endocrine, skin and neuronal tumors. We present a previously healthy 12-year-old boy with recurrent pain and swelling of the feet. One year later he presented with stiffness of the fingers...... and the toes were painful with no swelling. Rheumatoid factor, ANCA and ANA were all negative but cryoglobulins were positive. Unusual lentigines were noted. The monthly attacks with pain and joint swelling were treated sufficiently with prednisolone and azathioprine. Two years later he was admitted....... The lentigines and myxoma led to the suggestion of Carney Complex and the diagnosis was confirmed by a PRKAR1A mutation found in the child as well as the mother....

  8. A Case of Peripheral Ulcerative Keratitis Associated with Autoimmune Hepatitis

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    Hamoon Eshraghi

    2017-01-01

    Full Text Available Purpose. To describe a case of peripheral ulcerative keratitis in the setting of autoimmune hepatitis and possible overlap syndrome with primary sclerosing cholangitis. Case Report. A 48-year-old African American female with autoimmune hepatitis with possible overlap syndrome with primary sclerosing cholangitis presented with tearing, irritation, and injection of the left eye that was determined to be peripheral ulcerative keratitis. The patient was treated with topical and systemic steroids, immunosuppressant drugs (azathioprine and mycophenolate mofetil, a biologic (rituximab, and surgery (conjunctival resection, and the peripheral ulcerative keratitis epithelialized but ultimately led to corneal perforation. Conclusion. In this unique case, a patient with peripheral ulcerative keratitis who underwent treatment ultimately had a corneal perforation. This case may suggest a possible relationship between autoimmune hepatitis and peripheral ulcerative keratitis.

  9. Immunomodulatory Activity of Chlorophytum borivilianum Sant. F

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    Mayank Thakur

    2007-01-01

    Full Text Available Chlorophytum borivilianum Santapau & Fernandes (Liliaceae is a very popular herb in traditional Indian medicine and constitute a group of herbs used as ‘Rasayan’ or adaptogen. Ethanolic extract of the roots and its sapogenin were evaluated for their immunomodulatory activity. Effect of azathioprine-induced myelosuppresion and administration of extracts on hematological and serological parameters was determined. Administration of extracts greatly improved survival against Candida albicans infection. An increase in delayed-type hypersensitivity response (DTH, % neutrophil adhesion and in vivo phagocytosis by carbon clearance method was observed after treatment with extracts. Immunostimulant activity of ethanolic extract was more pronounced as compared to sapogenins. The results, thus justifies the traditional use of C. borivilianum as a rasayana drug.

  10. Immunomodulatory Activity of Chlorophytum borivilianum Sant. F.

    Science.gov (United States)

    Thakur, Mayank; Bhargava, Shilpi; Dixit, V K

    2007-12-01

    Chlorophytum borivilianum Santapau & Fernandes (Liliaceae) is a very popular herb in traditional Indian medicine and constitute a group of herbs used as 'Rasayan' or adaptogen. Ethanolic extract of the roots and its sapogenin were evaluated for their immunomodulatory activity. Effect of azathioprine-induced myelosuppresion and administration of extracts on hematological and serological parameters was determined. Administration of extracts greatly improved survival against Candida albicans infection. An increase in delayed-type hypersensitivity response (DTH), % neutrophil adhesion and in vivo phagocytosis by carbon clearance method was observed after treatment with extracts. Immunostimulant activity of ethanolic extract was more pronounced as compared to sapogenins. The results, thus justifies the traditional use of C. borivilianum as a rasayana drug.

  11. Hearing status in patients with rheumatoid arthritis.

    Science.gov (United States)

    Ahmadzadeh, A; Daraei, M; Jalessi, M; Peyvandi, A A; Amini, E; Ranjbar, L A; Daneshi, A

    2017-10-01

    Rheumatoid arthritis is thought to induce conductive hearing loss and/or sensorineural hearing loss. This study evaluated the function of the middle ear and cochlea, and the related factors. Pure tone audiometry, speech reception thresholds, speech discrimination scores, tympanometry, acoustic reflexes, and distortion product otoacoustic emissions were assessed in rheumatoid arthritis patients and healthy volunteers. Pure tone audiometry results revealed a higher bone conduction threshold in the rheumatoid arthritis group, but there was no significant difference when evaluated according to the sensorineural hearing loss definition. Distortion product otoacoustic emissions related prevalence of conductive or mixed hearing loss, tympanometry values, acoustic reflexes, and speech discrimination scores were not significantly different between the two groups. Sensorineural hearing loss was significantly more prevalent in patients who used azathioprine, cyclosporine and etanercept. Higher bone conduction thresholds in some frequencies were detected in rheumatoid arthritis patients that were not clinically significant. Sensorineural hearing loss is significantly more prevalent in refractory rheumatoid arthritis patients.

  12. The clinical extremes of autoimmune cholangitis

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    Sara Campos

    Full Text Available Autoimmune cholangitis (AIC was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC, but who were antimitochondrial (AMA negative and antinuclear antibodies (ANA positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1. AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2. In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH. The diagnostic differentiation between these diseases (AIC, PBC and AIH is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases.

  13. Drug therapy in Behçet's disease.

    Science.gov (United States)

    Okada, A A

    2000-06-01

    Behçet's disease is one of the most difficult forms of uveitis to treat. Variety in disease presentation and severity, as well as regional differences in standard of care, demand a tailor-made approach. Anterior segment inflammation generally responds to topical corticosteroids. However, the onset of posterior segment inflammation usually requires the advancement of treatment to periocular injections and/or oral administration of corticosteroids. Cyclosporin, either alone or in combination with corticosteroids, is considered in refractory patients. Other immunosuppressive drugs, such as azathioprine and chlorambucil, may be considered in difficult cases. Finally, preliminary results suggest efficacy with the immunomodulatory agent interferon alfa, although further clinical trials are necessary to evaluate safety and efficacy.

  14. [Primary chronic polyarthritis with kidney involvement (mesangiocapillary glomerulonephritis)].

    Science.gov (United States)

    Bürkle, P A

    1979-01-01

    A 34 year old white male patient suffering from seropositive "probable" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulo-nephritis. Rheumatoid factors (Latex test, Waaler-Rose titer) and IgM were markedly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within normal range. The rapid progression of the disease forced us to start an immunosuppressive drug therapy using azathioprine and steroids. Despite marked clinical improvement, e.g. normalisation of complement components, renal function, the disappearance of rheumatoid factor and proteinuria, the second biopsy taken two years later showed unchanged histological and immuno-histological changes of the glomerula.

  15. Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

    Directory of Open Access Journals (Sweden)

    Nicole Marijanovich

    2018-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25% and severe (+4 mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

  16. Dermatomyositis without Elevation of Creatine Kinase Presented as Bronchiolitis Obliterans Organizing Pneumonia

    Science.gov (United States)

    Lee, Young Ho; Choi, Seong Jae; Ji, Jong Dae; Shim, Jae Jeong; Kang, Kyung Ho; Cho, Hyun Deuk; Kim, Han Kyeom; Song, Gwan Gyu

    2000-01-01

    A case of dermatomyositis presented as bronchiolitis obliterans organizing pneumonia has been rarely reported. We describe a 46-year-old female patient with dermatomyositis without elevation of creatine kinase presented as bronchiolitis obliterans organizing pneumonia. She was treated with prednisolone and azathioprine. Over a 2-year follow-up she has had no elevation of creatine kinase. The patient remains asymptomatic and has no medication for dermatomyositis and bronchiolitis obliterans organizing pneumonia two years after initial treatment. It has been suggested that the prognosis of dermatomyositis without creatine kinase elevation may be poor. Because the prognosis of bronchiolitis obliterans organizing pneumonia is generally believed to be good, we tentatively suggest that the normal value of creatine kinase in dermatomyositis does not always seem to herald a poor prognosis, an associated malignancy or severe interstitial lung disease. PMID:10714098

  17. Active necrotizing cerebral vasculitis in systemic lupus erythematosus.

    Science.gov (United States)

    Goel, Deepa; Reddy, S Rajashekhar; Sundaram, Challa; Prayaga, Aruna K; Rajasekhar, Liza; Narsimulu, Gumdal

    2007-12-01

    Systemic lupus erythematosus (SLE) is a multisystemic disease with varied clinical manifestations. Focal cortical brain infarcts and CNS infections are the most common neuropathological features reported in most studies. This report describes a 32-year-old woman who had repeated episodes of strokes over 5 years. In view of polyarthritis, oral ulcers, presence of high titres of serum antinuclear antibodies, high titres of double-stranded DNA and strokes, she was treated as SLE. Despite prolonged immunosuppressive therapy with azathioprine and pulse cyclophosphamide, she succumbed to a brainstem stroke. Complete body autopsy showed multiple cerebral cortical and brainstem infarcts with fibrinoid necrosis of the vessel wall. Renal infarction with healed vasculitis and systemic vasculitis involving small vessels was seen. Extensive thrombosis was remarkable by its absence. Active necrotizing vasculitis of cerebral and renal vessels is a rare complication of SLE, which contributed to a fatal outcome in this patient.

  18. Successful treatment of neuro-Behçet’s disease with infliximab: four years follow-up

    Directory of Open Access Journals (Sweden)

    Manjinder Kaur

    2015-10-01

    Full Text Available Neuro-Behçet’s disease (NBD is a rare but severe manifestation of Behçet’s disease. Patients with NBD tend to have high morbidity and mortality. Some patients do not respond adequately to conventional therapy (corticosteroids and immunosuppressants. This has led to treatment gaps in the therapy of NBD. There are reports in the literature of patients with Behçet’s disease responding to anti-TNF therapy. We present a case of a male patient with biopsy proven cerebral vasculitis presenting as NBD who has been in remission with near resolution of cerebral magnetic resonance imaging lesions for 4 years following treatment with infliximab and azathioprine.

  19. Neuropsychiatric Systemic Lupus Erythematosus

    Science.gov (United States)

    Popescu, Alexandra; Kao, Amy H

    2011-01-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus. PMID:22379459

  20. Clinical Perspectives - Biologics in IBD: What's All the Fuss?

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    Hillary Steinhart

    2001-01-01

    Full Text Available Up until the present time, agents with relatively nonspecific anti-inflammatory or immunomodulatory effects such as 5-acetylsalicylic acid, corticosteroids and azathioprine have been the mainstay of inflammatory bowel disease medical therapy. These drugs have been quite useful in one or more clinical settings, but they have been hampered by modest efficacy, significant toxicity or both. With greater understanding of the specific pathways of the gut mucosal immune response, it is hoped that newer biologic response modifiers will provide better efficacy, with an improved adverse event profile compared with older existing therapies. This article examines the evidence behind the use of biologic therapies such as anti-tumour necrosis factor-alpha, interleukin-10, interleukin-11, anti-integrin antibody and antisense intercellular adhesion molecule-1 oligonucleotide.

  1. Endogenous Brucella endophthalmitis: A case report

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    Merih Oray

    2017-04-01

    Full Text Available Brucellosis may be associated with a wide range of ophthalmic manifestations including endophthalmitis, which is a sight-threatening condition that needs to be rapidly recognized and treated to avoid permanent visual loss. A 26-year-old female with a 6-month history of vision loss in the left eye was treated with high dose systemic corticosteroids and azathioprine with an initial misdiagnosis elsewhere. A dense vitreous haze with opacities at the posterior hyaloid and a wide area of retinochoroiditis led to the diagnosis of endogenous endophthalmitis at presentation to us. The vitreous sample and blood cultures demonstrated growth of Brucella melitensis. She received 6 months of systemic antibiotherapy, which resulted in resolution of inflammation; however, visual acuity remained poor due to irreversible damage. Infectious etiology, including brucellosis in endemic countries, has to be considered in the differential diagnosis before administering immunomodulatory therapy in patients with panuveitis of unknown origin.

  2. Hepatotoxicity by Drugs: The Most Common Implicated Agents

    Directory of Open Access Journals (Sweden)

    Einar S. Björnsson

    2016-02-01

    Full Text Available Idiosyncratic drug-induced liver injury (DILI is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov. According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab.

  3. Isolated septic arthritis of hip joint: a rare presentation of melioidosis. A case report.

    Science.gov (United States)

    Weerasinghe, N P; Herath, H M M; Liyanage, T M U

    2018-01-19

    Despite, Sri Lanka lies in the melioidosis endemic belt between 5°N and 10°N surrounded by countries known to have endemic melioidosis for many years, comparatively fewer cases of melioidosis infection have been reported in Sri Lanka. Melioidosis has a wide spectrum of clinical presentation, ranging from severe pneumonia to abscess formation in various organs. Isolated septic arthritis, which is a rare but well-recognized manifestation of melioidosis, could be the sole presenting problem in some patients with melioidosis. We report a middle aged diabetic female who has been on azathioprine for autoimmune hepatitis, presenting with pain and swelling of left hip joint. Investigations confirmed the clinical suspicion of septic arthritis, but all relevant microbiological investigations failed to isolate a causative organism. Due to the history of diabetes, possible immunosuppression with azathioprine, and failure to recognise the possible causative organism by initial investigations prompted us to investigate for melioidosis. Diagnosis of melioidosis was made by presence high titre of antibodies to melioidin antigen, and rapid response to appropriate treatment. The patient was treated with intravenous imipenem 1000 mg 6 hourly and oral cotrimoxazole (1920 mg 12 hourly) for 4 weeks followed by eradication therapy with cotrimoxazole and doxycycline. Given that melioidosis-induced septic arthritis share common features with septic arthritis due to other common pyogenic bacteria, differentiation of these two conditions is extremely difficult. Therefore, melioidosis needs to be considered as a possibility, when a patient with risk factors for melioidosis such as diabetes or immunosuppression presents with isolated septic arthritis. This case report has been presented to raise the awareness of an unusual presentation of melioidosis; isolated septic arthritis.

  4. Treatment of pemphigus vulgaris and pemphigus foliaceus: a systematic review and meta-analysis.

    Science.gov (United States)

    Atzmony, Lihi; Hodak, Emmilia; Gdalevich, Michael; Rosenbaum, Omer; Mimouni, Daniel

    2014-12-01

    No optimal therapeutic approach has been established for pemphigus. Our objective was to evaluate the efficacy, steroid-sparing effect, and safety of available treatment modalities. PubMed, LILACS (up to July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 5 of 12, May 2014), and the ClinicalTrials.gov registry and reference lists were searched for randomized controlled trials of any treatment modality for pemphigus vulgaris and pemphigus foliaceus. Data were extracted independently by two authors using predefined appraisal criteria and data fields. A total of 20 studies (826 participants) were included. Most were small and open-labeled; all but seven were not concealed for allocation. Owing to the variability in intervention arms, five meta-analyses were performed, each pooling the data of two to three trials. Studies excluded from the meta-analyses were described quantitatively. Azathioprine had a steroid-sparing effect but did not increase remission rate. Mycophenolate mofetil induced sustained remission more quickly than did placebo and delayed time to relapse but did not have a steroid-sparing effect or favorable remission rate. Cyclophosphamide had a steroid-sparing effect, though less than azathioprine, but did not affect the remission rate or time-to-disease control. Intravenous immunoglobulin had more favorable short-term efficacy than did placebo. Topical epidermal growth factor hastened lesion healing. Although some of the available therapeutic modalities for pemphigus are beneficial in terms of steroid-sparing, hastening response, or delaying relapse, none were found to increase the complete response rate compared with glucocorticoids alone, currently the mainstay of treatment. Multicenter randomized controlled trials and case control studies with uniform outcome measures are warranted.

  5. Low bone mineral density in children and adolescents with inflammatory bowel disease: a population-based study from Western Sweden.

    Science.gov (United States)

    Schmidt, Susanne; Mellström, Dan; Norjavaara, Ensio; Sundh, S Valter; Saalman, Robert

    2009-12-01

    Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD. To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine. BMD values were expressed as Z-scores using normative pediatric data from Lunar (GE Medical Systems). In this population-based study, the lowest BMD values were found in the lumbar spine. The entire IBD group showed significantly lower BMD Z-scores of the lumbar spine (L2-L4) in comparison to healthy references (-0.8 standard deviation [SD], range -5.9 to 3.7 SD, P < 0.001). Decreased BMD with a Z-score < -1 SD occurred in 46.7% of the individuals with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low BMD with a Z-score ≤ -2 SD was present in 26.7% of the patients with CD and in 24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as the depending variable, possible factors associated with lower BMD were male gender, low body mass index (BMI), and treatment with azathioprine. Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk factors for lower BMD are male gender, low BMI, and treatment with azathioprine, as a probable marker of disease course severity. Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.

  6. Neurosarcoidosis. Radiologe, Oct 2016, v. 56(10); Neurosarkoidose

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    Reith, W.; Roumia, S.; Popp, C. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-10-15

    Neurosarcoidosis is a relatively rare complication of sarcoidosis that occurs in approximately 5-15 % of patients. The clinical picture is variable. Clinically, neurosarcoidosis is mostly manifested as lesions of the cranial nerves (50-70 %) and several cranial nerves are typically affected. This is the result of aseptic granulomatous basal meningitis. Intraparenchymal granulomas also occur, frequently affecting basal near-midline structures, such as the hypothalamus and pituitary glands and can lead to encephalopathy. Diagnostics are essentially performed using magnetic resonance imaging (MRI) as it can demonstrate the thickened meninges, which have a high affinity for contrast media but the results are not specific. Particularly in the absence of systemic sarcoidosis, diagnosis can be difficult. Laboratory tests are not very sensitive and specific, which makes neurosarcoidosis a diagnostic challenge. Due to the substantial morbidity of the disease, early and consistent treatment should be initiated. This is usually carried out with corticosteroids supported by immunosuppressant drugs, such as azathioprine and methotrexate. (orig.) [German] Die Neurosarkoidose ist eine seltene Komplikation der Sarkoidose, die bei ca. 5-15 % der Patienten auftritt. Das klinische Bild ist variabel. Klinisch praesentiert sich eine Neurosarkoidose am haeufigsten mit Hinnervenausfaellen (50-70 %), typischerweise sind mehrere Hirnnerven betroffen. Dies ist Folge der aseptischen basalen granulomatoesen Meningitis. Auch intraparenchymatoese Granulome kommen vor, haeufig mit Befall basaler mittelliniennaher Strukturen wie Hypothalamus und Hypophyse, die zu einer Enzephalopathie fuehren koennen. Diagnostisch wegweisend ist die MRT, welche die verdickten und stark Kontrastmittel (KM) aufnehmenden Meningen nachweisen kann, die Befunde sind allerdings nicht spezifisch. Insbesondere bei fehlender systemischen Sarkoidose ist die Diagnose schwierig. Laboruntersuchungen sind wenig sensitiv und

  7. Assessment of the Prevalence and Risk Factors Associated With Glucocorticoid-Induced Diabetes Mellitus in Pemphigus Vulgaris Patients.

    Science.gov (United States)

    Darjani, Abbas; Nickhah, Nahid; Hedayati Emami, Mohammad Hassan; Alizadeh, Narges; Rafiei, Rana; Eftekhari, Hojat; Gharaei Nejad, Kaveh

    2017-06-01

    Pemphigus vulgaris is a chronic autoimmune disease and glucocorticoids are one of the main treatments. Our study investigates the prevalence and associated factors of glucocorticoid-induced diabetes mellitus in these patients under different glucocorticoid regimens. 36 patients with first diagnosed Pemphigus vulgaris based on pathological and direct immunofluorescence findings who had received different glucocorticoid regimens (1-2 mg/kg oral or 1-2 mg/kg oral with 1g methylprednisolone pulse daily for 3 consecutive days with or without azathioprine) were evaluated during 2014-2016. Our study found that 22.2% of patients had impaired fasting glucose and incidence of corticosteroid-induced diabetes mellitus was 22.2% with no difference between oral and pulse therapy of corticosteroid. The first day after pulse therapy 19 patients of 21 had post bolus hyperglycemia that 36% of them became diabetic after 8 weeks. None of the variables, including age, BMI, HbA1c, LDL, HDL, TG, cholesterol, family history and blood pressure were associated with diabetes. Pretreatment FBS was the factor that would increase the likelihood of glucocorticoid-induced diabetes mellitus, 42.2% of patients with pretreatment FBS 100-126 developed diabetes in comparison with 17.2% in normal pretreatment FBS. Although the group who received azathioprine was associated with increased incidence of diabetes, the overall corticosteroid dose in this group was significantly higher than the other group (P=0.012), and controversy with other studies could be because of difference in corticosteroid dosage and small number of patients. The incidence of diabetes was not different between the group with glucocorticoid pulses and oral prednisolone without pulse therapy. Higher pretreatment FBS can be related to increased incidence of diabetes, but results from this study due to small number of patients are preliminary and multicenter studies are needed.

  8. Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience.

    Science.gov (United States)

    Macaluso, Fabio Salvatore; Renna, Sara; Maida, Marcello; Dimarco, Mariangela; Sapienza, Chiara; Affronti, Marco; Orlando, Emanuele; Rizzuto, Giulia; Orlando, Rosalba; Ventimiglia, Marco; Cottone, Mario; Orlando, Ambrogio

    2017-09-01

    The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting. All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported. Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p = .01 and p = .03, respectively), and occurrence of nausea with Crohn's disease (p = .04). Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.

  9. Efficacy of immunosoppressive therapy and steroid sparing effect in interstitial lung disease associated to antisynthetase syndrome

    Directory of Open Access Journals (Sweden)

    G. De Marchi

    2011-09-01

    Full Text Available Objective: To evaluate the role of bronchoalveolar lavage (BAL in patients with interstitial lung disease associated to antisynthetase syndrome. Methods: We describe 5 patients, anti-Jo1 positive, with interstitial lung disease (lung fibrosis and/or diffusion capacity of CO <80%. Patients were monitored with lung function tests every 6 months, with high-resolution computed tomography (HRCT every 12 months, and with bronchoalveolar lavage (BAL at baseline and in the subsequent follow-up. Patients were treated as follows: a azathioprine with colchicine, or cyclosporine alone b cyclophosphamide when high neutrophil or eosinophil count on BAL was observed. Only low-dose steroids were used for mild muscular or articular involvement. Results: Pulmonary involvement remained stable in all patients at months +24. Lung function remained unchanged compared to the baseline evaluation; HRCT was stable in patients with fibrosis and no progression into fibrosis was observed in patients with ground glass areas at baseline. Bacterial pneumonia occurred in one patient treated with cyclophosphamide and resolved after antibiotic therapy. Conclusions: Clinical manifestations, instrumental tests and BAL may be of value to choice the best immunosuppressive therapy in the single case. An early less aggressive approach (azathioprine with colchicine, or cyclosporine alone may be useful. BAL could be performed when a progression of the lung involvement is demonstrated in the subsequent follow-up. Cyclophosphamide may be a valid alternative treatment in the presence of a neutrophilic or eosinophilic alveolitis. Efficacy and safety of the aforementioned immunosuppressive approach were observed in our series, avoiding prolonged high-dose steroid administration.

  10. Analysis of the data on pregnancy and lactation provided by patient information leaflets of anti-rheumatic drugs in Argentina.

    Science.gov (United States)

    Sabando, Miguel Ormaza; Saavedra, Maira Arias; Sequeira, Gabriel; Kerzberg, Eduardo

    2018-01-13

    To analyse the level of consistency and updating of the information on pregnancy and lactation provided by patient information leaflets (PILs) of the antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR Task Force recommendations on the use of anti-rheumatic drugs during pregnancy and lactation and the information provided by PILs of the same drugs approved in Argentina were analysed along with inconsistencies within the PILs of different registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were analysed. Out of the 88 PILs, 50% presented information inconsistencies as to pregnancy. Medications comprised in this group were: hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As for lactation, 56% had information inconsistencies. Medications encompassed in this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone, colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered trademark, information inconsistencies on pregnancy were found in the PILs of sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning lactation, inconsistencies were present in the PILs of hydroxychloroquine, sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half of the PILs of anti-rheumatic drugs analysed in this study had information inconsistencies on pregnancy and lactation. This is a serious state of affairs because the consensual decision-making process between patient and professional may be compromised, which, in turn, may give rise to medical-legal issues.

  11. [Classical medications in the treatment of inflammatory bowel diseases].

    Science.gov (United States)

    Duvnjak, Marko; Bilić, Ante; Barsić, Neven; Tomasić, Vedran; Stojsavljević, Sanja

    2013-04-01

    The treatment of inflammatory bowel diseases is complex and requires individual approach to every single patient. Traditionally, the approach is based on introduction of so called "classical" medication into the treatment regimen, from ones less potent and with fewer side effects to the ones more toxic but also therapeutically more effective. Aminosalicylates were the first choice of treatment for a long time. However, the role of aminosalicylates is becoming more and more diminished, although they are still the drug of choice in the treatment of mild to moderate ulcerative colitis. Corticosteroids are the therapy of choice in treatment of active IBD for achieving remission in moderate to severe disease. Azathioprine and 6- mercaptopurine belong to a group of thiopurines with an immunomodulatory effect which, in Crohn's disease as well as in ulcerative colitis, primarily have a role in a steroid dependant or steroid refractory type of disease and in maintenance of remission. Lately, early introduction of these medications is proposed to enhance the number of patients that remain in remission. Methotrexate is used for the therapy of active and relapsing Crohn's disease and represents an alternative in patients who do not tolerate or do not respond to azathioprine or 6-mercaptopurine therapy. Cyclosporine is used in treating steroid refractory ulcerative colitis and in some patients can postpone the need for colectomy. Antibiotics do not have a proven effect on the course of inflammatory bowel diseases and their primary role is to treat septic complications. Classic medications today represent a standard in the management of inflammatory bowel diseases, and the combination of the previously mentioned drugs often has a more potent effect on the course of the disease than any medication on its own and their combination is still an object of investigations and clinical studies.

  12. Epidermolysis bullosa acquisita with moderately severe dysphagia due to esophageal strictures

    Directory of Open Access Journals (Sweden)

    Jenny Tu

    2011-01-01

    Full Text Available Epidermolysis bullosa acquisita (EBA is a chronic, autoimmune condition involving the skin and mucous membranes. Symptomatic mucosal involvement is rare, but can impact on quality of life, due to esophageal strictures and dysphagia. We report a case involving a 60-year-old male presenting with bullous skin lesions on areas of friction on his hands, feet and mouth. Milia were visible on some healed areas. Biopsy showed a subepidermal vesicle. Direct immunofluorescence showed intense linear junctional IgG and C3 at the dermo-epidermal junction. Serological tests also supported the diagnosis of EBA. Screening tests for underlying malignancies were negative. Despite treatment with systemic steroids, the patient developed increasing dysphagia, requiring further investigation with esophagoscopy and a barium swallow. Confirmation of extensive esophageal stricturing prompted adjustment of medications including an increase in systemic steroids and addition of azathioprine. Currently, the patient′s disease remains under control, with improvement in all his symptoms and return of anti-basement membrane antibody levels to normal, whilst he remains on azathioprine 150 mg daily and prednisolone 5 mg daily. This case highlights the fact that the treatment of a given patient with EBA depends on severity of disease and co-morbid symptoms. Newer immunoglobulin and biological therapies have shown promise in treatment resistant disease. Considering that long-term immunosuppressants or biologicals will be required, potential side effects of the drugs should be considered. If further deterioration occurs in this patient, cyclosporin A or intravenous immunoglobulin (IV Ig will be considered. Vigilance for associated co-morbidities, especially malignancies, should always be maintained.

  13. [Coincidence of a chronic Hepatitis C and an autoimmune Hepatitis Type 3 - successful therapy with the new direct-acting antiviral agents].

    Science.gov (United States)

    Dikopoulos, N; Zizer, E

    2016-08-01

    Chronic hepatitis C infection may be associated with several features of autoimmunity (i. e., detection of different kinds of autoantibodies in the serum). Hepatitis C is also associated with different autoimmune diseases, such as autoimmune thyroiditis, lichen ruber planus, and membranous glomerulonephritis being the most relevant. There are very few cases of a coincidence of chronic hepatitis C with an autoimmune hepatitis, that is usually diagnosed by detection of specific autoantibodies and typical histological features. During the time of interferon-based antiviral therapies, we often faced a therapeutic dilemma as interferon could lead to an exacerbation of the coincident autoimmune disease. So, in these cases, a prophylactic immunosuppression had to be started before initiation of interferon therapy. Meanwhile, in the new era of direct antiviral agents against hepatitis C, highly specific and effective therapeutic options are available. The case report presented here describes the very rare coincidence of a chronic hepatitis C, genotype 1 with an autoimmune hepatitis type 3 diagnosed by the presence of anti-SLA-antibodies. In the past, the patient had several unsuccessful interferon-based therapies without achieving a sustained virological response in parallel with an immunosuppressive treatment with azathioprine. During the further course of the disease, the patient generated a liver cirrhosis CHILD A after only a few years. After the approval of the direct antiviral agents sofosbuvir and daclatasvir in 2014, we conducted an antiviral therapy, including ribavirin, for 24 weeks and fortunately achieved a sustained virological response. Due to the persistent disease activity caused by the autoimmune hepatitis after the end of antiviral therapy, we treated the patient with prednisolone and azathioprine and could induce a stable and persistent remission of the autoimmune disease. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Features Associated With, and the Impact of, Hemolytic Anemia in Patients With Systemic Lupus Erythematosus: LX, Results From a Multiethnic Cohort

    Science.gov (United States)

    DURÁN, SERGIO; APTE, MANDAR; ALARCÓN, GRACIELA S.; MARION, MIRANDA C.; EDBERG, JEFFREY C.; KIMBERLY, ROBERT P.; ZHANG, JIE; LANGEFELD, CARL D.; VILÁ, LUIS M.; REVEILLE, JOHN D.

    2009-01-01

    Objective To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. Methods SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. Results Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. Conclusion The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality. PMID:18759263

  15. Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists.

    Science.gov (United States)

    Taylor, K; Swan, D J; Affleck, A; Flohr, C; Reynolds, N J

    2017-06-01

    Little is known about U.K. dermatologists' treatment approaches towards adult patients with recalcitrant moderate-to-severe atopic eczema. We wanted to learn about (i) treatment approaches used for this disease in the U.K.; (ii) factors that influence treatment decisions and (iii) perceived gaps in evidence on treatment safety and efficacy, and priorities for future trials. We conducted an online survey of consultant-level dermatologists in the U.K. Sixty-one respondents from over 30 centres reported on management of moderate-to-severe atopic eczema in adults, outwith the context of an acute flare. Phototherapy or psoralen-ultraviolet A was the most common therapeutic modality chosen first line (46%), and this was usually narrowband ultraviolet B. Systemic therapy was chosen as a first-line approach by 36% of dermatologists. Azathioprine was the commonest drug reported being used as first line followed by oral corticosteroids, ciclosporin and methotrexate. Methotrexate was the most common second-line treatment of respondents. The key factors that influenced decision making on the use of phototherapy and systemic agents were the respondent's clinical experience, results of baseline tests (systemic agents) and knowledge of both efficacy and acute and chronic side-effect profiles. The most important evidence gaps identified were the relative effectiveness of treatments, the alternatives to current approaches and the safety of long-term maintenance treatment. With regard to future trials, respondents suggested that priority should be given to studies involving methotrexate. While survey study designs have limitations, we found that phototherapy, in particular narrowband ultraviolet B, was respondents' preferred first-line treatment for adults with recalcitrant moderate-to-severe atopic eczema, perhaps reflecting access to, and clinical experience of, this approach. Azathioprine is widely used as a longer-term maintenance treatment. © 2016 The Authors. British Journal

  16. Granulomatosis With Polyangiitis (Wegener’s)

    Science.gov (United States)

    Springer, Jason; Nutter, Benjamin; Langford, Carol A.; Hoffman, Gary S.; Villa-Forte, Alexandra

    2014-01-01

    Abstract To determine outcomes in relation to duration of maintenance therapy in patients with granulomatosis with polyangiitis (Wegener’s) (GPA), we conducted a retrospective chart review of patients with GPA seen at a single vasculitis center from 1992 to 2010. All patients achieved remission defined by a Birmingham Vasculitis Activity Score for Wegener Granulomatosis (BVAS/WG) of 0 with either cyclophosphamide or methotrexate. After achieving remission all patients were started on maintenance therapy with either methotrexate or azathioprine. The study comprised 157 patients with a median follow-up of 3.1 years. Using a univariate model, the continuation of maintenance medications for >18 months showed a 29% reduction in hazard ratio (HR) for relapse (HR, 0.71; 95% confidence interval [CI], 0.42–1.19; p = 0.19). Treatment for >36 months showed a 66% reduction in hazard ratio for relapse (HR, 0.34; 95% CI, 0.15–0.76; p = 0.008). When length of treatment was considered as a continuous factor, longer courses had an inverse relationship with the risk of relapse (HR, 0.70; 95% CI, 0.58–0.84; p < 0.001), which remained significant after adjusting for prednisone dose (HR, 0.59; 95% CI, 0.42–0.83; p = 0.003). Fifty-two percent of relapses occurred while the patients were off maintenance therapy. Among all patients who relapsed on therapy, 52% of those receiving methotrexate were on <15 mg/week, and 67% of those receiving azathioprine were on ≤50 mg/d. There were no differences between the short- and long-term maintenance therapy groups in overall adverse events or GPA-related morbidity. Discontinuation or use of low doses of maintenance therapy is associated with a higher relapse rate. PMID:24646464

  17. [A case of myasthenia gravis accompanied by steroid-resistant nephritic syndrome and CD57+ lymphocytes expansion in peripheral blood].

    Science.gov (United States)

    Miyamoto, N; Masaki, T; Nakamura, R; Motoyoshi, K; Kamakura, K

    1999-06-01

    A 38-year-old woman showed symptoms of myasthenia gravis (MG) three months after receiving thymectomy for malignant thymoma. She was treated with anti-acetylcholine esterase drugs and azathioprine over 10 years with two exacerbations, which were controlled by plasmapheresis and large amounts of steroid. Nephrotic syndrome developed suddenly at the age of 48, was progressive even after azathioprine withdrawal, and resistant to several immunosuppressive therapies such as steroids and cyclosporine A, and plasmapheresis. She died of systemic infection one-and-a-half years after the onset of nephrotic syndrome. Immunological studies revealed several abnormalities of cellular immunity. The expansion of gamma-delta T cells and CD57+ lymphocytes in peripheral blood was characteristic findings. These cells are thought to originate from the extrathymic process. Nephrotic syndrome has been thought to be sometimes complicated with thymoma. Although some pathogenetic possibilities about combination of nephrotic syndrome and thymoma were supposed, none has yet been clarified. As we noticed the remarkable increase in the number of CD57+ cells, we examined its proportion in the peripheral blood of patients with MG and/or thymoma, as well as in individuals without sickness. The study revealed the expansion of CD57+ cells in MG thymoma patients (32.3 +/- 15.9%), compared with healthy controls (15.2 +/- 5.4%), MG non-thymoma patients (20.3 +/- 11.5%), and thymoma non-MG patients (15.2 +/- 12.0%) statistically (Mann-Whitney's U test). Therefore, we supposed that the peripheral CD57+ cell expansion was associated with parathymic immunological abnormalities, such as MG, thymoma, and nephrotic syndrome.

  18. Eosinophilia in a patient with cyclical vomiting: a case report

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    Fitzgerald S Matthew

    2004-05-01

    Full Text Available Abstract Background Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. Case presentation The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7–10 days, with each episode lasting for 1–3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. Conclusions The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3, granulocyte macrophage colony stimulating factor (GM-CSF and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.

  19. [Hypomethylation and multiple sclerosis, the susceptibility factor?].

    Science.gov (United States)

    Cara Terribas, C J; González Guijarro, L

    2002-03-01

    Azathioprine, off-label used long time ago to treat multiple sclerosis (MS) patients, has recently received approval from the Spanish Medicine Agency (Agencia Española del Medicamento) in relapsing-remitting (RR) forms of this condition. Clinical efficacy of azathioprine is due to the enzymatic conversion to 6-thioguanine (the active metabolite). The key enzyme in this process is thio purine methyl transferase (TPMT), converting 6-MP to 6-methylMP. A specific genetic polymorphism has been described affecting this enzyme. With the aim of optimizing purine therapy in a variety of autoimmune diseases, monitoring of TPMT phenotype has been performed in a vast number of patients. The TPMT activity frequency distribution histogram from a Spanish population sample has been compared with the corresponding ones to Crohn's disease, ulcerative colitis and MS patients. TPMT activity has been studied in red blood cells obtained from 3,640 clinical laboratory samples in Spain of which 1,249 corresponded to patients affected by Crohn's disease, 589 to ulcerative colitis, 348 to MS, 487 to several autoimmune diseases apart from the previously mentioned and 967 to a group of blood donors. The mean TPMT activity in the MS group (17.1 6.1 U/ml) was significantly lower (p < 0.001) than in Crohn's disease (20.0 5.8 U/ml), ulcerative colitis (19.7 6.1 U/ml) and donors group (19.9 6.3 U/ml). Defective methylation profile and subsequent hyperhomocysteinemia leading to a widespread impairment of the methyl-transferase activity (in this case affecting MBP methylation) is a vicious circle we propose as a MS susceptibility factor.

  20. Risk factors for neuropsychiatric manifestations in children with systemic lupus erythematosus: case-control study.

    Science.gov (United States)

    Zuniga Zambrano, Yenny Carolina; Guevara Ramos, Juan David; Penagos Vargas, Nathalia Elena; Benitez Ramirez, Diana Carol; Ramirez Rodriguez, Sandra Milena; Vargas Niño, Adriana Carolina; Izquierdo Bello, Alvaro Hernando

    2014-09-01

    Neuropsychiatric symptoms in children with systemic lupus erythematosus cause high morbidity and disability. This study analyzed risk factors associated with neuropsychiatric presentation in patients with systemic lupus erythematosus aged lupus erythematosus who were hospitalized with or without neuropsychiatric symptoms was collected between March 2007 and January 2012. Clinical variables, laboratory examinations, neuroimages, and disease activity (Systemic Erythematosus Lupus Disease Activity Index) and damage (Systemic Lupus International Collaborating Clinics) indices were analyzed. A total of 90 patients were selected, 30 with neuropsychiatric symptoms. The patients' average age was 12.2 years. The most common neuropsychiatric symptoms were seizures, migraine, and depression. The average Systemic Erythematosus Lupus Disease Activity Index was 19.86 (S.D. 10.83) and the average Systemic Lupus International Collaborating Clinics index was 2.02 (S.D. 2.43), with higher values in patients with neuropsychiatric symptoms (P = 0.001). The levels of complement C3 and C4 were significantly higher in patients with a neuropsychiatric disorder (P = 0.003). Lupus anticoagulant was found in 51.5% of patients with neuropsychiatric symptoms (odds ratio, 3.7; 95% confidence interval, 1.3-10.0). Immunosuppression with azathioprine, rituximab, or cyclophosphamide delayed the time to neuropsychiatric systemic lupus erythematosus development by 18.5 months (95% confidence interval, 10.6-26.5) compared to patients who did not receive these agents. The presence of lupus anticoagulant was a risk factor in our patients. The use of immunosuppressants, such as cyclophosphamide, rituximab, and azathioprine, delayed the presentation of neuropsychiatric manifestations of lupus. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Cytomegalovirus infection causes morbidity and mortality in patients with autoimmune diseases, particularly systemic lupus: in a Chinese population in Taiwan.

    Science.gov (United States)

    Tsai, W P; Chen, M H; Lee, M H; Yu, K H; Wu, M W; Liou, L B

    2012-09-01

    To investigate the clinical outcome of cytomegalovirus (CMV) infection in febrile hospitalized patients with autoimmune diseases, mostly systemic lupus erythematosus (SLE). Fifty-four febrile patients were analyzed retrospectively. Half were diagnosed as CMV infection, by positive CMV pp65 antigenemia assay. Clinical and laboratory data between two groups were compared. Correlation between laboratory data and SELENA-SLEDAI scores/mortality were analyzed in the CMV infection group. Receiver operating characteristic analysis was performed to determine the cutoff points of different parameters for predicting mortality or morbidity. The CMV infection group received a higher corticosteroid dosage (mean 26.3 mg/day) and a higher percentage of azathioprine use before admission than the non-CMV infection group. In the former, the deceased subgroup had a significantly higher number of infected leukocytes for CMV (shortened as CMV counts, P = 0.013), more cases of bacterial infection (P = 0.090), and a higher SLE disease activity index score (P = 0.072) than the alive subgroup. The CMV infection group had lower lymphocyte count and more positive bacterial infection than the non-CMV infection group did (P = 0.013 and P = 0.027, respectively). A level of 25 CMV particles/5 × 10(5) polymorphonuclear neutrophils (PMN) was the best cutoff point for predicting CMV-associated mortality, with a sensitivity of 75.0% and specificity of 72.2%. Moderate dose (30 mg/day) of prednisolone or azathioprine use predisposes patients with autoimmune diseases to CMV infection with concurrent bacterial infection. In particular, peak CMV counts at 25/5 × 10(5) PMN or low lymphocyte counts predict mortality or morbidity, respectively.

  2. Esquistossomose mansoni experimental: carga parasitária e distribuição de vermes adultos no sistema porta de ratos albinos tratados com Azatioprina

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Moreira Campos

    1983-09-01

    Full Text Available Estudou-se o curso da infecção esquistossomótica experimental no rato albino, um hospedeiro singular para o Schistosoma mansoni, e quatro semanas após a infecção houve uma rápida diminuição na carga parasitária, fato esse denominado por alguns pesquisadores como ' fenômeno de autocura Contudo, após a administração de um imunossupressor - a Azatioprina - observou-se uma maior susceptibilidade dos ratos à infecção, com os animais apresentando um significativo retardamento no chamado "fenômeno de autocura A grande maioria dos vermes é recuperada nos vasos intra-hepáticos do sistema porta, sem que haja migração para as veias mesentéricas. Quando os ratos foram tratados com Azatioprina observou-se uma significativa localização mesentérica dos vermes adultos neste hospedeiro.The course of experimental Schistosoma mansoni infection in the albino rat, a singular host for schistosomes was studied. Four weeks after infection there was a decrease of worm burden, a sélf-cure phenomenon reported by other investigators. However, after administration of a immunosupressive drug - Azathioprine - an increase in susceptibility of rats to infection was observed, with the animals presenting a significant delay in the to period selfcure. The majority of worms were recovered from the intra-hepatic veins of the portal system, but there was no migration to mesenteric veins. When rats were treated with Azathioprine a significant mesenteric localization of schistosomes was observed in this host.

  3. Treatment of Adults with Idiopathic Recurrent Pericarditis: Novel Use of Immunotherapy.

    Science.gov (United States)

    Schwier, Nicholas C; Hale, Genevieve M; Davies, Marie L

    2017-03-01

    Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed first-line treatment consisting of aspirin (ASA) or a nonsteroidal antiinflammatory drug (NSAID) in combination with colchicine therapy, recurrences still occur in greater than 20% of patients. Many patients then require treatment with long-term corticosteroids, which is not a favorable option due to their short- and long-term adverse effects. Because it is theorized that the pathophysiology of IRP may possess autoimmune sequelae, the use of immunotherapy for the treatment of IRP has emerged. In this review, we describe the literature associated with immunotherapy used to treat IRP in an adult population as well as provide an overview of the safety and monitoring parameters for each agent. The most common immunotherapies used after patients have had multiple recurrences of IRP are anakinra, intravenous immunoglobulin (IVIG), and azathioprine. In most cases, these immunotherapies are adjunctive therapy, with the goal of tapering and discontinuing immunosuppressive corticosteroids. After reviewing the data, anakinra resulted in more patients discontinuing corticosteroids and prevented further recurrences of pericarditis. IVIG resulted in symptom resolution and no further recurrences in most of the patients. Azathioprine was associated with more than half of patients becoming recurrence free; however, many patients required a restart of corticosteroids due to recurrence. Clinicians should be aware of the adverse effects of immunotherapy, ranging from mild gastrointestinal events to risk of infection and serious blood dyscrasias that may require diligent monitoring. The use of immunotherapy for the treatment of adults with IRP should be restricted to patients who have multiple recurrences. Ideally, immunotherapy would be adjunctive to first-line combination therapy with ASA/NSAID plus colchicine, with the goal of tapering and discontinuing immunosuppressive

  4. Recurrent Pericarditis: Modern Approach in 2016.

    Science.gov (United States)

    Imazio, Massimo; Adler, Yehuda; Charron, Philippe

    2016-06-01

    Recurrent pericarditis is one of the most troublesome complications of pericarditis occurring in about one third of patients with a previous attack of pericarditis. The pathogenesis is presumed to be autoimmune and/or autoinflammatory in most cases. The mainstay of therapy for recurrences is physical restriction and anti-inflammatory therapy based on aspirin or NSAID plus colchicine. Corticosteroids at low to moderate doses (e.g., prednisone 0.2 to 0.5 mg/kg/day) should be considered only after failure of aspirin/NSAID (and more than one of these drugs) or for specific indications (e.g., pregnancy, systemic inflammatory diseases on steroids, renal failure, concomitant oral anticoagulant therapy). One of the most challenging issues is how to cope with patients who have recurrences despite colchicine. A small subset of patients (about 5 %) may develop corticosteroid-dependence and colchicine resistance. Among the emerging treatments, the three most common and evidence-based therapies are based on azathioprine, human intravenous immunoglobulin (IVIG), and anakinra. After failure of all options of medical therapy or for those patients who do not tolerate medical therapy or have serious adverse events related to medical therapy, the last possible option is the surgical removal of the pericardium. Total or radical pericardiectomy is recommended in these cases in experienced centers performing this surgery. A stepwise approach is recommended starting from NSAID and colchicine, corticosteroid and colchicine, a combination of the three options (NSAID, colchicine and corticosteroids), then azathioprine, IVIG, or anakinra as last medical options before pericardiectomy.

  5. Long term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1996-01-01

    Purpose: To evaluate the short and long term effects of total lymphoid irradiation (TLI) in the treatment of allograft rejection in cardiac transplant patients. Materials and Methods: From 1986 to 1995, 48 courses of TLI were delivered to 47 patients who had received cardiac transplants at Stanford University. In 38 cases, TLI was administered for chronic, intractable allograft rejection despite conventional anti-rejection therapy, including corticosteroids, azathioprine, cyclosporine, OKT3, DHPG, RATG, and methotrexate. Ten patients received TLI prophylactically, beginning radiation between 5 and 16 days after heart transplantation. The prescribed radiation dose was 800 cGy given in 80 cGy fractions twice weekly to all major lymph node regions using mantle and inverted Y fields. Patients continued to receive all medications except azathioprine which was held during TLI to prevent severe marrow suppression. All patients were closely monitored for episodes of rejection, infection, prednisone requirements, blood counts, and complications of treatment. Post-irradiation follow up ranged from 6 months to 9.1 years with a mean of 3.1 years. Results: The actual mean dose of radiation was 730 cGy delivered over a mean of 39 calendar days. Fifty six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, the frequency of rejection dropped from 0.46 episodes/patient/month before radiation to 0.14 episodes/patient/month during TLI (p 3 during TLI (p = 0.01) and remained low at 167.6 cells/mm 3 2-4 months after treatment (p = 0.05). CD8+ lymphocytes also decreased during treatment from 233.2 to 65.8 cells/mm 3 (p = 0.003) but rose significantly above normal to 381.3 cells/mm 3 2-4 months after TLI (p 0.05). Thus, the ratio of helper/suppresser T-cells was chronically decreased. Infection rates were not significantly different before, during or after

  6. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy.

    Science.gov (United States)

    Nørgård, Bente Mertz

    2011-12-01

    during pregnancy our data suggest. No significantly increased overall relative risk of congenital abnormalities and no significantly increased risks of selected congenital abnormalities. After exposure to 5-aminosalicylic acid during pregnancy our data suggest. No significantly increased relative risk of low birth weight, intrauterine growth retardation or congenital abnormalities (evaluated overall). A significantly increased relative risk of preterm birth and stillbirth in ulcerative colitis women, compared to women with no prescription of reimbursed medicine in pregnancy - and also after comparing with women with chronic inflammatory bowel disease not taking 5-aminosalicylic acid during pregnancy. It is not clear whether these associations are causal or influenced by confounding by disease activity in particular. After maternal exposure to azathioprine/6-mercaptopurine during pregnancy our data suggest. An increased relative risk of preterm birth, congenital abnormalities, and perinatal mortality - also after using controls with similar underlying diseases. It is difficult to rule out an influence of uncontrolled confounding. These were the first published data from a controlled observational study on exposed women with chronic inflammatory bowel disease. After preconceptional paternal use of azathioprine/6-mercaptopurine our data suggest An increased risk of congenital abnormalities, although not significantly increased. The birth outcomes in women with Crohn's disease are examined in nationwide sub-cohorts classified according to type of anti-inflammatory drug exposure during pregnancy, and based on data from the Danish National Hospital Discharge Registry, the nationwide Danish Prescription Database and the Danish Medical Birth Registry. Furthermore, birth outcomes are examined in Crohn's disease women with disease activity during pregnancy, based on data from review of hospital records, the Danish National Hospital Discharge Registry and the Danish Medical Birth

  7. Tratamiento sistémico del penfigoide cicatrizal ocular Systemic treatment of ocular cicatricial pemphigoid

    Directory of Open Access Journals (Sweden)

    María Cecilia Juri

    2012-04-01

    received azathioprine, cyclophosphamide and ciclosporine. Seventeen received oral steroids in addition to immunosuppresive drugs. Four patients combined two immunosupressive drugs to control their disease. In three refractory cases IV immunoglobulin (Ig was administered with good response. From 48 evaluated patients, 39 improved with treatment, eight remained stable and one progressed. In our experience, methotrexate and azathioprine were effective drugs, with low toxicity. Dapsone was useful in mild cases, with frequent adverse effects. IVIg was effective for refractory cases.

  8. Autoimmune diseases and pregnancy: analysis of a series of cases.

    Science.gov (United States)

    Gomes, Vânia; Mesquita, Alexandra; Capela, Carlos

    2015-06-04

    An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid

  9. Colectomy is a risk factor for venous thromboembolism in ulcerative colitis.

    Science.gov (United States)

    Kaplan, Gilaad G; Lim, Allen; Seow, Cynthia H; Moran, Gordon W; Ghosh, Subrata; Leung, Yvette; Debruyn, Jennifer; Nguyen, Geoffrey C; Hubbard, James; Panaccione, Remo

    2015-01-28

    To compare venous thromboembolism (VTE) in hospitalized ulcerative colitis (UC) patients who respond to medical management to patients requiring colectomy. Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by: (1) responsive to inpatient medical therapy (n=382); (2) medically refractory requiring emergent colectomy (n=309); and (3) elective colectomy (n=329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course (i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications (i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios (OR) with 95%CI. The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparin prophylaxis. In contrast, VTE was higher among patients who underwent an emergent (8.7%) and elective (4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal (45.8%) followed by lower extremity (19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective (adjusted OR=3.69; 95%CI: 1.30-10.44) and emergent colectomy (adjusted OR=5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time (adjusted OR=1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities

  10. Arterite de Takayasu: aspectos clínicos e terapêuticos em 36 pacientes Takayasu's arteritis: clinical and therapeutic aspects in 36 patients

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    Marília Duarte Brandão Panico

    2008-06-01

    Full Text Available CONTEXTO: A arterite de Takayasu é uma vasculite crônica, geralmente com diagnóstico tardio devido à pouca especificidade dos sintomas durante a fase inicial do acometimento vascular. A terapêutica de eleição é o uso de imunossupressores. O procedimento cirúrgico, quando necessário, é sempre evitado na fase aguda. OBJETIVO: Descrever alterações clínicas, laboratoriais e vasculares de arterite de Takayasu no período de 1977 a 2006. MÉTODO: A amostra compreendeu 36 pacientes - 10 brancos, 35 mulheres, idade média de 31,7 anos (±13,7, com prevalência significante na quarta década (p 60 mm em 50% da amostra (p 3 mm, 1,7, 1,2 e BACKGROUND: Takayasu arteritis is a chronic vasculitis often with delayed diagnosis due to the nonspecific presentation of clinical symptoms in its initial phase. Treatment includes imunosuppression drugs. Surgical treatment, when necessary, should be avoided in the acute phase. OBJECTIVE: To describe clinical, laboratory and vascular findings in Takayasu's arteritis from 1977 through 2006. METHODS: The sample was comprised of 36 patients (10 Caucasians, 35 women, mean age of 31.7 (±13.7 years, and significant prevalence in the forth decade (p 60 mm in 50% of the sample (p 3 mm (41.6%, 1.7 (19.4%, 1.2 (8.37%, and < 1.2 mm (30.50% (p < 0.005. Glucocorticoids were used in 61%, azathioprine in 16.6%, and azathioprine combined with cyclophosphamide in 8.3%. Surgical and endovascular procedures were performed in 30.5%. Two patients died due to cardiovascular diseases. CONCLUSIONS: Carotid intima-media thickness, PCR, and ESR are important markers for the follow-up of Takayasu's arteritis. Delay in diagnosis is an important issue for Takayasu's progression, since it may reduce morbidity and mortality rates.

  11. Cost-Utility Analysis of Infliximab with Standard Care versus Standard Care Alone for Induction and Maintenance Treatment of Patients with Ulcerative Colitis in Poland.

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    Stawowczyk, Ewa; Kawalec, Paweł; Pilc, Andrzej

    2016-05-01

    To assess the cost-effectiveness of infliximab with standard care (e.g., azathioprine, prednisolone, mesalazine, and 6-mercaptopurine) versus standard care alone for induction and maintenance treatment of patients with ulcerative colitis (UC) in Poland. Cost-utility decision analytic model. A Markov model was used to estimate the expected costs and effects of infliximab/standard care and standard care alone. For each treatment option, costs and quality-adjusted life-years (QALYs) were calculated to estimate the incremental cost-utility ratio. The target population consisted of a hypothetical cohort of adult patients with moderately to severely active UC who had an inadequate response to standard treatment, including corticosteroids and 6-mercaptopurine or azathioprine, or who were intolerant to or had medical contraindications to such therapies. The analysis was performed from the perspective of the Polish public payer over a 30-year time horizon. The clinical parameters were derived mainly from the Active Ulcerative Colitis Trial (ACT) 1 and ACT 2 and from the Ulcerative Colitis Long-term Remission and Maintenance with Adalimumab (ULTRA) 2 clinical trial. Different costs and utility values were assigned to the various health states in the model; utility values were derived from a previously published study. Treatment of patients who received infliximab/standard care instead of standard care alone resulted in 0.174 additional QALYs. Treatment with infliximab/standard care was found to be more expensive than treatment with standard care alone from the Polish National Health Fund perspective. The incremental cost-utility ratio of infliximab/standard care compared with standard care alone was estimated to be 402,420 Polish zlotys (PLN)/QALY gained (95% confidence interval [CI] 253,936-531,450 PLN/QALY gained), which is equivalent to $106,743 (U.S. dollars)/QALY gained (95% CI $67,357-140,968 [U.S. dollars]/QALY gained). Treatment with infliximab/standard care instead

  12. Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

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    Pavlisa Goran

    2009-10-01

    Full Text Available Abstract Background Neuromyelitis optica (NMO is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS and NMO is important, as optimum treatment for both diseases may differ considerably. Case Presentation We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM, having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. Conclusion In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

  13. Treatment of neuromyelitis optica: an evidence based review

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    Douglas Sato

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS, and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

  14. "ALS reversals": demographics, disease characteristics, treatments, and co-morbidities.

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    Harrison, Daniel; Mehta, Paul; van Es, Michael A; Stommel, Elijah; Drory, Vivian E; Nefussy, Beatrice; van den Berg, Leonard H; Crayle, Jesse; Bedlack, Richard

    2018-04-02

    To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with "amyotrophic lateral sclerosis (ALS) reversals" and those with typically progressive ALS. Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study.

  15. Progressive Multifocal Leukoencephalopathy and Systemic Lupus Erythematosus: Focus on Etiology

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    Shala Ghaderi Berntsson

    2016-03-01

    Full Text Available Progressive multifocal leukoencephalopathy (PML caused by reactivation of the JC virus (JCV, a human polyomavirus, occurs in autoimmune disorders, most frequently in systemic lupus erythematosus (SLE. We describe a HIV-negative 34-year-old female with SLE who had been treated with immunosuppressant therapy (IST; steroids and azathioprine since 2004. In 2011, she developed decreased sensation and weakness of the right hand, followed by vertigo and gait instability. The diagnosis of PML was made on the basis of brain MRI findings (posterior fossa lesions and JCV isolation from the cerebrospinal fluid (700 copies/ml. IST was immediately discontinued. Cidofovir, mirtazapine, mefloquine and cycles of cytarabine were sequentially added, but there was progressive deterioration with a fatal outcome 1 year after disease onset. This report discusses current therapeutic choices for PML and the importance of early infection screening when SLE patients present with neurological symptoms. In the light of recent reports of PML in SLE patients treated with rituximab or belimumab, we highlight that other IST may just as well be implicated. We conclude that severe lymphopenia was most likely responsible for JCV reactivation in this patient and discuss how effective management of lymphopenia in SLE and PML therapy remains an unmet need.

  16. Antibiotics and probiotics in inflammatory bowel disease: why, when, and how.

    Science.gov (United States)

    Prantera, Cosimo; Scribano, Maria Lia

    2009-07-01

    To summarize recent evidence on the role of intestinal bacteria in inflammatory bowel diseases, and of antibiotics and probiotics in their treatment. The implications connected with the use of antibiotics are also examined. The hypothesis that Mycobacterium paratuberculosis could be a causative agent of Crohn's disease has not been confirmed by a large trial on symptomatic patients treated by a combination of antibiotics active against this bacterium. An increased number of adherent-invasive Escherichia coli have been found in the intestinal tissue of patients with Crohn's disease, but their role in the pathogenesis of this condition remains to be defined. The combination of metronidazole and azathioprine, associating the effects of a reduced bacterial load with immunosuppression, appears to be a therapeutic option to decrease the recurrence of postoperative Crohn's disease in high-risk patients. However, concerns are raised by the possibility that antibiotics may induce disease relapse due to Clostridium difficile infection. Recent literature provides increasing support for the use of antibiotics in Crohn's disease, although the side effects limit their long-term use. The efficacy of antibiotics in ulcerative colitis is not confirmed by the available literature, except in severe colitis. More trials are needed to support the use of probiotics as therapy in inflammatory bowel disease.

  17. A designated centre for people with disabilities operated by St Joseph's Foundation, Limerick

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  18. Steroid sparing regimens for management of oral immune-mediated diseases

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    Arti Agrawal

    2014-01-01

    Full Text Available Immune-mediated mucocutaneous disease may present oral symptoms as a first sign of the disease. The primary etiology could be the cellular and/or humoral immune responses directed against epithelial or connective tissue, in a chronic and recurrent pattern. Lichen planus, pemphigus vulgaris and bullous pemphigoid are the most frequent immunologically mediated mucocutaneous diseases. More often than not, patients present with complaints of blisters, oral ulcers, pain, burning sensation, and bleeding from the various oral sites. Steroids, whether topical or systemic, are the treatment of choice as they have both anti-inflammatory and immune-suppressant properties; however, challenges in the treatment of autoimmune diseases are the complexity of symptoms, the need to manage long-term medications for preserving organ function, and the long-term adverse effects of steroids. In such situations steroid sparing agents, such as, tacrolimus, dapsone, azathioprine, cyclosporine, and so on, may be helpful. Here an attempt is made to review various treatment regimens that could be used as alternatives to steroids for management of such diseases.

  19. Pemphigus vulgaris in a Welsh pony stallion: case report and demonstration of antidesmoglein autoantibodies.

    Science.gov (United States)

    Winfield, Laramie D; White, Stephen D; Affolter, Verena K; Renier, Anna C; Dawson, Dominic; Olivry, Thierry; Outerbridge, Catherine A; Wang, Yu Hsuan; Iyori, Keita; Nishifuji, Koji

    2013-04-01

    To describe the clinical, histological and immunological findings of an equine case of pemphigus vulgaris, including the demonstration of antidesmoglein (anti-Dsg) autoantibodies. The diagnosis of pemphigus vulgaris was confirmed in a 9-year-old Welsh pony stallion with both direct and indirect immunofluorescence and immunoprecipitation studies, the latter identifying circulating anti-Dsg3 IgG. Treatment with immunosuppressive medications was initiated. Lesions were seen in the perineal area, sheath, mane, tail, eyelids, coronary bands and mucosa of the mouth and oesophagus. Initial corticosteroid treatment improved the clinical signs, but the onset of laminitis necessitated a reduction in dosage, which was associated with a recurrence of lesions and development of oral ulcers. A corneal ulcer developed after 60 days of treatment. Despite treatment with azathioprine, gold salts and dapsone, the disease progressed and the pony was euthanized. Postmortem examination showed additional lesions of the cardia of the stomach. Pemphigus vulgaris is rarely diagnosed in equids. We describe a case that was substantiated by the demonstration of anti-Dsg3 IgG. Response to treatment was poor, with the best response to high doses of prednisolone. Equine pemphigus vulgaris is likely to carry a poor prognosis and if there is no response to treatment, humane euthanasia is warranted. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

  20. Evaluation of cases of pemphigus vulgaris and pemphigus foliaceus from a reference service in Pará state, Brazil*

    Science.gov (United States)

    Pires, Carla Andréa Avelar; Viana, Viviane Brito; Araújo, Fernando Costa; Müller, Silvia Ferreira Rodrigues; de Oliveira, Miguel Saraty; Carneiro, Francisca Regina Oliveira

    2014-01-01

    BACKGROUND Pemphigusis a bullous, rare and chronic autoimmune disease. There are two major forms of pemphigus: vulgaris and foliaceus. Epidemiological data and clinical outcome in patients diagnosed in the Brazilian Amazon states are still rare. OBJECTIVES To study the occurrence of the disease during the study period and analyze the epidemiological profile of patients, the most common subtype of pemphigus, and the clinical evolution of patients. METHODS Retrospective analysis of medical records of hospitalized patients with pemphigus foliaceus and pemphigus vulgaris in the period from 2003 to 2010 in Dermatology Service of Hospital Fundação Santa Casa de Misericórdia do Pará, Belém, Northern Brazil. RESULTS We found a total of 20 cases of pemphigus during the study period, 8 of which were of foliaceus pemphigus and 12 of vulgaris pemphigus. Pemphigus foliaceus had the predominance of male patients (75%), showed satisfactory clinical evolution, and was characterized by absence of pediatric cases. Pemphigus vulgaris affected more women (66.7%), showed mean hospital stay of 1 to 3 months (50%), and there were three cases of death (25%). The prescribed immunosuppressive drugs included prednisone with or without combination of azathioprine and/or dapsone. Sepsis was associated with 100% of the deaths. CONCLUSIONS The occurrence of the disease is rare, there are no familiar/endemic outbreaks in the sample. Evolution is usually favorable, but secondary infection is associated with worse prognosis. The choice of best drugs to treat pemphigus remains controversial. PMID:25054740

  1. Transition from Pemphigus Foliaceus to Pemphigus Vulgaris: Case Report with Literature Review

    Science.gov (United States)

    Park, Sang Gun; Chang, Jae Yong; Cho, Young-Hun; Kim, Soo-Chan

    2006-01-01

    The transition between the main subtypes of pemphigus, pemphigus vulgaris (PV), and pemphigus foliaceus (PF) has rarely been reported. Moreover, the development of PV in a patient with PF is much more unusual than that of PF in a patient with PV. We report a 48-year-old man who presented with cutaneous lesions showing the typical clinical and histological features of PF. Five years later, his skin lesions became extensive and he developed oral erosions. His condition did not respond well to steroids and azathioprine. Histological examination of a vesicle disclosed suprabasal acantholysis in contrast to the subcorneal acantholysis discovered upon initial histological evaluation. Indirect immunofluorescence revealed IgG antikeratinocyte cell surface antibodies at a titer of 1:640. The titer was 1:160 at initial diagnosis. Upon immunoblotting, the patient's serum reacted with 130 kiloDalton (kDa) and 160 kDa proteins, suggesting desmoglein (Dsg) 3 and 1, respectively. We herein report an unusual case of PV that developed from PF during the disease's flare-up. PMID:16642562

  2. Treatment of Intraepidermal Autoimmune Bullous Diseases Sürekli Eğitim

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    Tamer İrfan Kaya

    2011-06-01

    Full Text Available Pemfigus is an autoimmune bullous skin disease, characterized by intraepidermal blisters. It is a severe and potentially life-threatening chronic disease with blisters and erosions on the mucosae and the skin. Treatment options do not differ for two most common types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, except that the latter is usually less resistant to treatment and corticosteroids can often be started at lower doses. Systemic corticosteroids are still the most widely used drugs in the treatment of pemphigus and continue to be the mainstay of therapy for this disease. Adjuvant drugs are commonly used in combination with the aims of increasing efficacy and of having a steroid-sparing action, thereby allowing reduced corticosteroid side-effects. Mortality and complete remission rates have improved since the introduction of adjuvant drugs to pemphigus. Adjuvant drugs include immunoadsorbtion, corticosteroid pulse therapy, intravenous immunoglobulin (IVIG, immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate mofetil and and anti-CD20 monoclonal antibody (rituximab. The lack of consensus in the published literature about the treatment of this disorder is responsible for different treatment strategies. Treatments need to be chosen after careful consideration of the potential benefits and side effects according to the patients’ medical condition. Here, both conventional therapies and novel treatment regimens for pemphigus are discussed. (Turkderm 2011; 45 Suppl 1: 44-53

  3. Evaluation of cases of pemphigus vulgaris and pemphigus foliaceus from a reference service in Pará state, Brazil.

    Science.gov (United States)

    Pires, Carla Andréa Avelar; Viana, Viviane Brito; Araújo, Fernando Costa; Müller, Silvia Ferreira Rodrigues; Oliveira, Miguel Saraty de; Carneiro, Francisca Regina Oliveira

    2014-01-01

    Pemphigusis a bullous, rare and chronic autoimmune disease. There are two major forms of pemphigus: vulgaris and foliaceus. Epidemiological data and clinical outcome in patients diagnosed in the Brazilian Amazon states are still rare. To study the occurrence of the disease during the study period and analyze the epidemiological profile of patients, the most common subtype of pemphigus, and the clinical evolution of patients. Retrospective analysis of medical records of hospitalized patients with pemphigus foliaceus and pemphigus vulgaris in the period from 2003 to 2010 in Dermatology Service of Hospital Fundação Santa Casa de Misericórdia do Pará, Belém, Northern Brazil. We found a total of 20 cases of pemphigus during the study period, 8 of which were of foliaceus pemphigus and 12 of vulgaris pemphigus. Pemphigus foliaceus had the predominance of male patients (75%), showed satisfactory clinical evolution, and was characterized by absence of pediatric cases. Pemphigus vulgaris affected more women (66.7%), showed mean hospital stay of 1 to 3 months (50%), and there were three cases of death (25%). The prescribed immunosuppressive drugs included prednisone with or without combination of azathioprine and/or dapsone. Sepsis was associated with 100% of the deaths. The occurrence of the disease is rare, there are no familiar/endemic outbreaks in the sample. Evolution is usually favorable, but secondary infection is associated with worse prognosis. The choice of best drugs to treat pemphigus remains controversial.

  4. The management of pemphigus vulgaris in a burn intensive care unit: a case report and treatment review.

    Science.gov (United States)

    Miletta, Nathanial; Miller, Mary E; Lam, Thomas; Chung, Kevin K; Hivnor, Chad

    2014-01-01

    Pemphigus vulgaris is a rare, potentially fatal, autoimmune blistering disease of the skin and mucous membranes. Treatment of this disease is problematic because of a lack of high-grade, evidence-based recommendations, the side-effect profiles of the therapies available, and the extensive supportive care that afflicted patients require. The authors present the unfortunate course of a patient with severe pemphigus vulgaris who was admitted to the U.S. Army Institute of Surgical Research Burn Center, to demonstrate the potential complications of therapy. Given the patient's complex course, the authors reviewed the literature and share in this article the most up-to-date treatment recommendations for patients with pemphigus vulgaris. The authors' review of the literature supports using conventional therapy consisting of high-dose corticosteroids and an adjuvant immunosuppressant for mild to moderate cases of pemphigus vulgaris. The immunosuppresants recommended are mycophenolate mofetil, azathioprine, and cyclophosphamide, in order of preference, based on their side-effect profiles and steroid-sparing effects. For severe or recalcitrant cases of pemphigus vulgaris, the authors recommend adding rituximab as early as possible. If increased risk of infection is of particular concern, the use of intravenous immunoglobulin in place of rituximab is advised.

  5. A Case of Subacute Cutaneous Lupus Erythematosus in a Patient with Mixed Connective Tissue Disease: Successful Treatment with Plasmapheresis and Rituximab

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    M. Fantò

    2013-01-01

    Full Text Available A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE. Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX (375 mg/m2 weekly for 4 weeks. Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed.

  6. Myasthenia Gravis in Pregnancy: A Case Report

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    Sebastian Berlit

    2012-01-01

    Full Text Available Objective. To present a case of maternal myasthenia gravis in pregnancy and give a systematic review of the literature. Case. We report the case of a 38-year-old parturient with a life-threatening complication of immune-mediated myasthenia gravis shortly after an elective cesarean section on patient's request under spinal anesthesia at 35 + 3 weeks of gestation. The newborn was transferred to the pediatric unit for surveillance and did not show any signs of muscular weakness in the course of time. The mother developed a respiratory insufficiency on the second day postpartum. The myasthenic crisis led to a progressive dyspnoea within minutes, which exacerbated in a secondary generalized seizure with cardiac-circulatory arrest. After successful cardiopulmonary resuscitation, the patient was transferred to intensive care. The interdisciplinary therapeutic approach included ventilatory assistance via endotracheal intubation, parenteral pyridostigmine, azathioprine, and steroids. By interdisciplinary measures, a stable state was regained. Conclusion. Myasthenia gravis especially when associated with pregnancy is a high-risk disease. As this disease predominantly occurs in women of reproductive age, it is important to be aware of this condition in obstetrics and its interdisciplinary diagnostic and therapeutic management.

  7. Metastatic Crohn's disease in pediatrics

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    Javier Blasco-Alonso

    Full Text Available Introduction: Metastatic Crohn's disease (MCD is an extraintestinal manifestation of Crohn's disease, with biopsy as fundamental diagnostic tool. There are few References to MCD in children, with a 0.5-1% estimated incidence in adults. There is no consensus about its therapeutic approach. We describe our diagnostic and therapeutic experience in MCD. Case Reports: Four cases of MCD are described in our Pediatric Gastroenterology Unit in a tertiary care hospital. The age at diagnosis was between 7 and 13 years. Lesions appeared before the diagnosis of Crohn's disease in three of them, and during the course of the disease in another one, with genital location in three patients and bilateral pretibial region in the other. All four cases demonstrated non-caseificant granulomas on biopsy. Only two patients used exclusive enteral nutrition therapy with complete resolution, while other two cases received a combination of therapies (corticosteroids, azathioprine, tacrolimus, infliximab and adalimumab because of recurrence. Only one case required surgery after poor clinical control. Discussion: The MCD is infrequent but must always be included in the differential diagnosis of cutaneous lesions in Crohn's disease, considering it could be the debut of the disease. We will rely on biopsy anyway for definitive diagnosis. In this series the genital region is verified as the most commonly affected in children. The therapeutic approach does not differ from the management of intestinal involvement.

  8. Effect of blood transfusions on canine renal allograft survival

    International Nuclear Information System (INIS)

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-01-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted

  9. Effect of blood transfusions on canine renal allograft survival

    International Nuclear Information System (INIS)

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-01-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted

  10. Predictors of thickened carotid intima media thickness among well controlled lupus nephritis patients in a Malaysian tertiary centre

    Directory of Open Access Journals (Sweden)

    N.CT. Kong

    2012-12-01

    Full Text Available Objectives. To investigate the prevalence of thickened carotid intima media thickness (CIMT and its associated risk factors in patients with lupus nephritis (LN who were in remission. Methods. This was a cross sectional study in which consecutive LN patients who were in remission and attending our Nephrology/SLE Clinic were included. Their demographic profile, traditional cardiovascular risk factors and treatment medications were evaluated by clinical interview and review of medical records. Carotid intima media thickness (CIMT was measured using B Mode carotid ultrasonography. CIMT was considered to be abnormally thickened if it exceeded the 75th percentile matched for age-and sex-matched normal controls. The associated factors for thickened CIMT were examined. Results. A total of 39 patients with a mean remission duration of 29±24.3 months and on a mean prednisolone dose of 9.10±7.83 mg daily completed the study. Six patients (15.4% had thickened CIMT. On univariate analysis, male gender, patient age, older age at diagnosis, higher serum CRP levels, greater proteinuria and higher mean cumulative azathioprine dose were associated with thickened CIMT (PConclusions. Lupus factors particularly age at diagnosis and proteinuria were the associated factors of thickened CIMT. Larger prospective trials are indicated to confirm our findings.

  11. A patient with systemic lupus erythematosus and lupus nephritis: A 12-year follow-up

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    Jovanović Nataša

    2011-01-01

    Full Text Available Introduction. Systemic lupus erythematosus (SLE is a chronic immunological disease causing a significant morbidity and mortality in younger women and involving several organs and systems, most often the kidneys, being consequently the incidence of lupus nephritis (LN about 60%. Case report. We reported a 57 year-old patient with the diagnosed SLE in 1995. Pathohistological analysis of kidney biopsy revealed LN type V. The patient was treated with corticosteroid pulses and azathioprine during one year. A remission was achieved and maintained with prednisone, 15 mg daily. Nephrotic relapse was diagnosed in 2006 and the second kidney biopsy revealed recent kidney infarction due to extensive vasculitis. Soon, a cerebrovascul insult developed and CT-scan revealed endocranial infarctus. The patient was treated with corticosteroids and cyclophosphamide pulses (totally VI monthly pulses, and also with low-molecular heparine, anticoagulants and salicylates because of the right leg phlebothrombosis. After the pulses, the patient was adviced to take prednisone 20 mg daily and azothioprine 100 mg daily, and 6 months later mycophenolate mofetil because of persistent active serological immunological findings (ANA 1 : 320 and nephrotic syndrome. Mycophenolate mofetil was efficient in inducing and maintaining remission of nephrotic syndrome. Conclusion. The aim of LN treatment is to achieve and maintain remission, improve patients’ outcome, reduce the toxicity of immunosuppressive drugs and the incidence of relapses. Mycophenolate mofetil was shown to be efficient in inducing and maintaining remission of nephrotic syndrome in the frame of LN.

  12. Outcome of therapy in biopsy proven lupus nephritis with cyclophosphamide or mycophenolate: Registry data from a South Indian tertiary care center

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    Keerthi Talari

    2017-01-01

    Results: Eighty-three patients (75 females with the mean age of 25 ± 8.9 years were included. The median duration of follow-up was 18 months (range: 6–153. Forty-one patients had Class IV, 19 Class III, 11 Class V, 7 Class III/IV + V, and 5 Class II LN. Forty received high-dose cyclophosphamide (HD CyC, 14 Euro-Lupus Nephritis Trial cyclophosphamide (ELNT CyC, 20 mycophenolate mofetil (MMF for induction, while two received azathioprine, one cyclosporine, one modified ponticelli, and five with Class II nephritis received no induction. Baseline characteristics were comparable between three groups. The response rate was similar between the three groups: 30/40 in the HD CyC group, 12/14 in the ELNT CyC group, and 15/20 in the MMF group responded at the end of induction (P = 0.69. Complete response rate was higher in the individuals who received cyclophosphamide (HD CyC + ELNT CyC as compared to MMF (17/34 vs. 2/13, P = 0.05. Univariate analysis of factors predicting response revealed only class of nephritis as a significant factor predicting response (complete or partial at the end of induction therapy. Conclusion: In this South Indian lupus registry a complete response at 6 months in biopsy-proven LN was better with cyclophosphamide than mycophenolate.

  13. Late response to rituximab in a dialysis patient with severe lupus nephritis

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    Magdi M Hussein

    2013-01-01

    Full Text Available Although recently completed controlled trials failed to demonstrate a significant effect of rituximab on the clinical outcome in non-renal and renal lupus, there is growing evidence from case reports and open-label trials that the use of this medication is successful in certain subgroups of patients including refractory cases and helps in reducing the dose of steroids. We present a 26-year-old female who failed to respond to a long-course treatment with prednisolone, cyclophosphamide, mycophenolate mofetil and azathioprine and who went on to develop end-stage renal disease requiring commencement of regular maintenance hemodialysis. Ten days before starting dialysis, she was given rituximab, and a second dose was given 17 days after starting dialysis. After 7 months on dialysis, the patient began to regain kidney function and is now off dialysis for 11 months. To the best of our knowledge, this is the first case report of a lupus patient on dialysis treated with rituximab in whom dialysis could be stopped and who remained off this therapy up till now, after an observation period of 1 year.

  14. Treatment of intractable lupus nephritis with total lymphoid irradiation

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    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  15. Drug hypersensitivity syndrome

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    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  16. Influence of patient medication on diagnostic accuracy in nuclear medicine

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    Sampson, C.B. [Addenbrooke`s Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine

    1997-12-31

    Full text. In recently years many reports have published of unusual or unexpected changes in the biodistribution of radiopharmaceuticals which do not correlate with normality or disease. Whilst many extraneous factors can alter tracer kinetics it has become apparent that concomitant patient medication can be such a factor. If the clinician is unaware that patient is on drug therapy difficulties arise in making a accurate diagnosis. Most drug/radio pharmaceutical effects are those in which the functional status of the organ is altered as a result of the pharmacological action of the drug. Examples here are narcotic analgesics such as methadone, pethidine and morphine which cause spasm of the biliary tract due to contraction of the sphincter of Oddi and an altered transit time of the technetium labelled tracer. Cytotoxic drugs such as cyclophosphamide and vincristine can markedly affect tumour uptake of 67-gallium so that litter or no activity is taken up by the tumour. Nifedipine, because of its powerful calcium channel blocking activity is known to affect the radiolabelling of white cells and red cells and to affect uptake of Tc-99 m MDP into bones. Other important and confusing effects are caused by phenothiazines, cimetidine and oral contraceptives. In recent years it has been reported that drugs such as cyclosporin, azathioprine and heparin and derivatives of heparin can markedly interfere with cell labelling procedures. This review will consider some of the clinical effects of drugs and will also address the reporting of instances of drug/radio pharmaceutical interactions

  17. Common Variable Immunodeficiency Associated with Hepatosplenic T-Cell Lymphoma Mimicking Juvenile Systemic Lupus Erythematosus

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    A. A. Jesus

    2011-01-01

    Full Text Available Common variable immunodeficiency (CVID is a heterogeneous disorder with susceptibility to infections, autoimmune manifestations, and cancer. To our knowledge, CIVD with T-cell lymphoma mimicking juvenile systemic lupus erythematosus (JSLE was not described in the literature, and one case was reported herein. An 8-year-old female was admitted in our Pediatric Immunology Unit with a clinical history of hypogammaglobulinemia, recurrent upper respiratory infections, and pneumonias. She had a marked decrease of three serum immunoglobulin isotypes, and the diagnosis of CVID was established. At the age of 17 years, she presented with oral ulceration, nonerosive arthritis, nephritis, serositis, cytopenia, positive antiphospholipid antibodies, and positive antinuclear antibody fulfilling the American College of Rheumatology (ACR criteria for SLE. She was treated with intravenous methylprednisolone for three consecutive days, and intravenous immunoglobulin, and maintenance therapy of chloroquine, azathioprine and prednisone 40 mg/day. Two months later, she died of septic shock secondary to acute pneumonia. The necropsy showed hepatosplenic T-cell lymphoma with diffuse involvement of bone marrow, spleen, liver, and lungs. The lymphoma cells were positive for CD3 immunostaining and negative for CD20 and lysozyme. In conclusion, the association of CVID and hepatosplenic T-cell lymphoma may simulate JSLE diagnosis.

  18. Idiopathic pulmonary hemosiderosis in a 9-year-old girl

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    Kamienska E

    2009-12-01

    Full Text Available Abstract Diffuse alveolar hemorrhage (DAH is a rare and life-threatening condition characterized by hemoptysis, dyspnoea, alveolar infiltrates on chest radiograph and various degrees of anemia. It may occur either as a primary disease of the lungs or a secondary condition due to cardiac, systemic vascular, collagen or renal diseases. Idiopathic pulmonary hemosiderosis (IPH is a separate form of DAH of unknown origin, associated in some cases with celiac disease. The estimated incidence of IPH in children is 0.24-1.23 cases per million, with a mortality rate as high as 50%. Only about 500 cases of this disease have been described in medical literature. We present a case of a 9-year-old girl diagnosed with IPH, which was confirmed by the presence of many hemosiderin-laden macrophages in bronchoalveolar lavage obtained by bronchofiberoscopy. Therapy with glucocorticoids was initiated with a partial and transient response. Azathioprine and a gluten-free diet were subsequently introduced. However, the girl still suffers from recurrent episodes of hemoptysis, dyspnea and anemia.

  19. Golimumab in unresponsive ulcerative colitis

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    Lippert E

    2014-05-01

    Full Text Available Elisabeth Lippert, Martina Müller, Claudia Ott University Hospital Regensburg, Department of Internal Medicine I, Regensburg, Germany Abstract: Ulcerative colitis (UC is a chronic inflammation mainly affecting the colon mucosa. It predominantly occurs in younger patients. Until recently, the main goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain, and weight loss, by using mesalazine and steroids. With newer medications, such as immunomodulators (thiopurines and the biologics providing blockade of tumor necrosis factor (TNF, the goals of the therapy in UC have changed to long-term remission and mucosal healing. The first available anti-TNF therapy in UC included infusion therapy with infliximab every few weeks. In 2012, subcutaneously administered adalimumab gained approval for the treatment of UC in Germany. In patients with a mild disease, therapy with mesalazine, orally or topically, can be sufficient. In patients with moderate to severe disease, therapy with azathioprine or anti-TNF is often required to reach disease control; however, this is only efficient in about two-thirds of patients. Some patients either show no response or a lost response while on treatment. So, further medical options are warranted in the treatment of UC. With golimumab, a new approach in the treatment of mild to moderate UC recently became available in Germany and is a promising new option in the therapy regimen for patients with UC. Keywords: anti-TNF, biological therapy, inflammatory bowel disease

  20. Immunosuppression in lung transplantation.

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    Scheffert, Jenna L; Raza, Kashif

    2014-08-01

    Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

  1. Long-term follow-up and treatment of congenital alveolar proteinosis.

    Science.gov (United States)

    Griese, Matthias; Ripper, Jan; Sibbersen, Anke; Lohse, Pia; Lohse, Peter; Brasch, Frank; Schams, Andrea; Pamir, Asli; Schaub, Bianca; Muensterer, Oliver J; Schön, Carola; Glöckner-Pagel, Judith; Nicolai, Thomas; Reiter, Karl; Hector, Andreas

    2011-08-17

    Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known. A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child. The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.

  2. Diagnosis and therapy of autoimmune hepatitis.

    Science.gov (United States)

    Granito, Alessandro; Muratori, Paolo; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Lenzi, Marco; Bianchi, Francesco B; Muratori, Luigi

    2009-06-01

    Autoimmune hepatitis (AIH) is a chronic progressive hepatitis, characterized by interface hepatitis with lymphoplasmacellular infiltrates on liver biopsy, high serum globulin level and circulating autoantibodies. It is classified into two types, according to autoantibody profile: type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; type 2 by anti-liver kidney microsomal type 1 (anti-LKM-1) antibodies. AIH affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. The diagnosis of AIH is based on a scoring system codified by an international consensus. Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with AIH and results in remission induction in over 80% of patients. Alternative proposed strategies in patients who have failed to achieve remission on standard therapy or patients with drug toxicity include the use of cyclosporine, tacrolimus, budesonide or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease, however AIH can recur or develop de novo after liver transplantation.

  3. Autoimmune liver disease 2007.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

    2008-01-01

    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  4. Comparative study of efficacy of excimer light therapy vs. intralesional triamcinolone vs. topical 5% minoxidil for alopecia areata: an observational study

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    Zo Nun Sanga

    2015-06-01

    Full Text Available Introduction. Alopecia areata (AA is a chronic inflammatory disease that involves hair follicles, and sometimes nails, caused by a T-cell mediated autoimmune mechanism. Current treatment modalities include corticosteroids (oral, topical or intralesional, minoxidil, contact sensitizers (DNCB, DPCP and SADBE, immunosuppressants (methotrexate or azathioprine, DMARDs (sulfasalazine, and phototherapy. Objective. To compare the efficacy of excimer light therapy, intralesional triamcinolone and 5% topical minoxidil. Material and methods. After taking consent, 40 patients were treated with excimer light, 46 patients with intralesional triamcinolone injection and 14 patients with 5% topical minoxidil. The results were compared by their photographs taken prior to treatment, at 2 months and 6 months of follow-up. Results. Among the excimer group, 21/32 (61.76% patients with a single patch and 1/6 (16.67% with multiple patches achieved > 50% hair regrowth. In the triamcinolone group, 23/30 (76.67% with a single patch and 10/16 (62.5% with multiple patches achieved > 50% hair regrowth, and in the minoxidil group, 4/12 (33.33% with a single patch and none, i.e. 0/2, with multiple patches achieved > 50% regrowth. Conclusions. After comparing the efficacy of excimer light therapy, intralesional triamcinolone and 5% minoxidil, it was concluded that intralesional triamcinolone seems to be the most efficacious. Multiple AA patches were more resistant than a single patch. Scalp response was much better than beard.

  5. Comparative study of efficacy of excimer light therapy vs intralesional triamcinolone vs topical 5% minoxidil: an observational study

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    Zonunsanga

    2015-01-01

    Full Text Available Introduction: Alopecia Areota is a chronic inflammatory disease that involves hair follicles, and sometimes nails, caused by T-cell mediated autoimmune mechanism. Current treatment modalities includes corticosteroids (oral, topical or intralesional, Minoxidil, Contact sensitizers like DNCB, DPCP and SADBE, Immunosuppressants like Methotrexate or Azathioprine, DMARDs like Sulfasalazine, and Phototherapy. Materials and methods: After taking consent, 40 patients treated with excimer light, 46 patients treated with triamcinolone injection intralesionally and 14 patients treated with topical minoxidil 5% were compared by their photographs taken prior to treatments, at 2 months and 6 months follow up. Results: Among the excimer group, 21/32 (61.76% with single patch and 1/6 (16.67% with multiple patches achieved >50% hair regrowth. Among Triamcinolone group, 23/30 (76.67% with single patch and 10/16 (62.5% with multiple patches achieved >50% hair regrowth. Among the Minoxidil group, 4/12 (33.33% with single patch and none .i.e 0/2 with multiple patches achieved >50% regrowth. Conclusion: After comparing the efficacy of Excimer light therapy, intralesional triamcinolone and 5% Minoxidil, it was concluded that intralesional triamcinolone seems to be the most efficacious. Multiple patches were more resistant than single patch. Scalp response much better than beard.

  6. September 2014 imaging case of the month

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    Gotway MB

    2014-09-01

    Full Text Available No abstract available. Article truncated at 150 words. Clinical History: A 57-year-old non-smoking woman presented to her physician as an outpatient with complaints of worsening cough, fever, chills, and shortness of breath. The patient’s past medical history includes systemic lupus erythematosus diagnosed 18 years earlier, for which the patient has been variably treated with corticosteroids, hydroxychloroquine, and azathioprine. Additional past medical and surgical history includes migraines, mood disorder, diabetes mellitus treated with metformin, hysterectomy for endometriosis, and iron-deficient anemia. The patient was also diagnosed with small lymphocytic lymphoma 3 years earlier following a right breast biopsy when an abnormal opacity was discovered incidentally at routine screening breast imaging. She has not been treated for this neoplasm as no B symptoms have been reported. Frontal and lateral chest radiography (Figure 1 was performed. Which of the following statements regarding the chest radiograph is most accurate? 1. The chest radiograph shows asymmetric pulmonary vascularity; 2. The chest radiograph shows bilateral ...

  7. June 2017 critical care case of the month

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    Fountain S

    2017-06-01

    Full Text Available No abstract available. Article truncated after 150 words. History of Present Illness: The patient is a 60-year-old woman who presented with a month long history of odynophagia with retrosternal pain and occasional nausea and vomiting. Past Medical History, Social History and Family History: She has a past medical history of mixed connective tissue disease with anti-phosopholipid antibody. There is also a history of leukocytoclastic vasculitis, chronic leg ulcers, and poor dentition. She also has a history of chronic obstructive lung disease (COPD and is a current smoker having accumulated about 50 pack-years of cigarette smoking. Current Medications: prednisone 20 mg daily, azathioprine 75 mg daily, plaquenil 400 mg daily, salmeterol/fluticasone BID, albuterol prn. Electrocardiographic, Radiologic and Laboratory Evaluation: Her electrocardiogram and chest x-ray were unremarkable. Complete blood count showed a white blood cell count of 10,500 cells per microliter (mcL, hemoglobin 10.3 grams/deciliter (dL, hematocrit 31%, and platelet count of 48,000 cells per mcL. Electrolytes were unremarkable and …

  8. A Patient with Autoimmune Pancreatitis Type 1 with Previously Known Lymphadenopathy, Both in the Context of IgG4-related Disease.

    Science.gov (United States)

    Alidjan, Fazil M; Karim, Faiz; Verdijk, Rob M; van Esser, Joost W; van Heerde, Marianne J

    2015-11-05

    Autoimmune pancreatitis (AIP) is an important clinical pathologic concept of IgG-4-related disease. AIP is a rare cause of chronic pancreatitis, characterized by a fibroinflammatory process by lymphoplasmacytic infiltrates, storiform fibrosis, obliterative phlebitis, and increased IgG4+ plasma cells, leading to dysfunction of the pancreas. Affected patients with AIP frequently have disease affecting other organs or sites with similar histologic changes, elevated IgG4+ plasma cell infiltrate, and good response to corticosteroid therapy. These diseases often are not limited to the pancreas and the pancreas may not be involved at all. We report a 62-year-old man with obstructive jaundice with pre-existent submandibular lymphadenopathy. Diagnosis of AIP was based on diagnostic criteria by the HISORT-criteria in combination with elevated IgG-4 serum levels. CT revealed a focal enlargement of the head of the pancreas, as well as mesenteric peripancreatic and mediastinal lymphadenopathy. He was treated with high-dose steroid in combination with azathioprine and showed good clinical response. We report a case with pre-existent submandibular lymphadenopathy and obstructive jaundice based on AIP type 1, both in the context of IgG4-related disease.

  9. 6-Mercaptopurine and Inflammatory Bowel Disease: Hidden Ground for the Cytomegalovirus

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    LC Hookey

    2003-01-01

    Full Text Available 6-Mercaptopurine (6-MP and azathioprine are important drugs for the treatment of inflammatory bowel disease (IBD but their actions suppress host defense against infection. A challenging case of a 19-year-old female patient with quiescent Crohn’s disease maintained with 6-MP presenting with dyspnea and a normal chest exam and x-ray is presented. She became ventilator-dependent and only after numerous investigations was diagnosed with cytomegalovirus (CMV pneumonitis. A systematic literature review of CMV infections in IBD patients was performed. The present case is the first report of a patient with quiescent IBD maintained on 6-MP who developed CMV pneumonitis. Other reports have identified patients with active disease on multiple immunosuppressants who developed CMV pneumonitis and also highlight the risk of CMV colitis in refractory IBD. The authors review the approach to the diagnosis of CMV infections in IBD patients with atypical pneumonia and colitis and highlight the importance of considering CMV infection in these settings.

  10. A case of aortitis syndrome diagnosed by digital subtraction angiography

    International Nuclear Information System (INIS)

    Tamaki, Atsushi; Sakai, Masashi; Yano, Kimio

    1984-01-01

    A 45-year-old female was admitted to our hospital with complaints of anemia, hypertension, and a dull, throbbing pain in the right side of the neck. On physical examination, a pulsating tumor in the right side of the neck and a ''to-and-fro'' murmur at the right 2nd intercostal space were noted. Laboratory tests revealed ESR 90 mm/hour and CRP 5+. Digital subtraction angiography (DSA) showed an aneurysm distal to the narrowing of the right common carotid artery, in addition to winding and narrowing of the right vertebral and the left common carotid arteries. These findings are typical of Type I aortitis syndrome. Aortogram showed aortic regurgitation (AR). Furthermore, we found the presence of HLA Bw52 and a conspicuous increase of tromboxane B 2 . Treatment involving a combination of prednisolone, azathioprine and estriol was effective, resulting in marked improvement of the patient's general condition as well as laboratory test results. In cases of aortitis syndrome combined with an aneurysm of a large artery and AR, direct opacification of the aorta with a catheter is occasionally hazardous and is difficult to perform repeatedly. DSA is useful in such circumstances because it can be performed repeatedly with little risk and it offers an image as clear as these obtained by direct injection of contrast medium in the aorta. (author)

  11. Multiple sclerosis and Capgras' syndrome.

    Science.gov (United States)

    Sidoti, Vincenzo; Lorusso, Lorenzo

    2007-11-01

    Psychotic disorders in patients with multiple sclerosis (MS), although reported in the literature, are quite rare. The maniac psychosis is increased in MS patients, especially after steroid use, but a pure paranoid (delusional) state is very uncommon. We report a case of a patient with MS complicated by Capgras' syndrome. This disorder, characterized by misidentification and also known as "illusion of double", was first described by the French psychiatrist Joseph Capgras in 1923. Our patient was a 36-year-old female, with a negative psychiatric history; the diagnosis of MS dated back to the age of 18. Subsequently, after a treatment with high dosage of steroids for optic neuritis, her psychiatric symptoms (delusion of references) began and she was then treated with clozapine. Thereafter she had repeated relapses. Immunomodulatory treatments with beta-interferon first and azathioprine then were stopped for intolerance. She came to our hospital for a new relapse with severe dynamic ataxia. After a treatment with corticosteroids the patient developed a paranoid disorder characterized by persecutory delusion (illusion of double) towards her husband. Treatment with glatiramer acetate and quetiapine improved her neuropsychiatric condition.

  12. Ustekinumab as an Alternative Treatment Option for Chronic Pityriasis Rubra Pilaris

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    Mudit Chowdhary

    2015-03-01

    Full Text Available Pityriasis rubra pilaris (PRP is an exceptionally rare, chronic inflammatory dermatosis of unknown etiology. Patients classically present with small, follicular keratosis and salmon-colored plaques that begin at the head and neck and slowly progress to widespread erythroderma including the palms and soles. It is difficult to distinguish PRP from other inflammatory dermatoses; however, features that help aid in the diagnosis include ‘islands' of spared skin, orangish hue and typical findings on biopsy. There are no specific guidelines on therapy and treatment options include corticosteroids, vitamin D analogs, retinoids, methotrexate, cyclosporine, azathioprine and tumor necrosis factor alpha antagonists. Unfortunately options are limited for patients when these drugs do not work. We report a case of chronic PRP, refractory to conventional treatment, successfully treated with ustekinumab monotherapy. The patient was treated with 90 mg subcutaneous ustekinumab injections and began to show improvement within only 8 weeks. Long-term control of the disease has been attained without any significant side effects. We report this case to show that ustekinumab can be used as an alternative treatment method for patients with chronic, unremitting PRP. Treatment response is remarkably rapid and the infrequent dosing leads to patient compliance and a significantly improved quality of life.

  13. Idiopathic Nephrotic Syndrome in Childhood: A Retrospective Analysis of Two Hundred and Eighty Nine Patients

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    Kenan Yılmaz

    2017-12-01

    Full Text Available Aim: In this study, we aimed to evaluate the demographic and histopathological characteristics and response to medications in children with idiopathic nephrotic syndrome in Turkey. Methods: We reviewed medical records of patients older than one year, who were newly diagnosed with nephrotic syndrome and had been followed for at least one year in our department between November 1994 and March, 2013. Results: A total of 289 children (169 boys were included in the study. Fifty theree patients (18.4% were with steroid-resistant nephrotic syndrome, 33 (11.4% with frequently relapsing nephrotic syndrome and 53 (18.4% were with steroid-dependent nephrotic syndrome. Cyclosporine A (CsA, cyclophosphamide, mycophenolate mofetil, levamisole, azathioprine, and rituximab were used as steroid-sparing agents in some patients. The number of patients who were responder to steroid and to CsA was similar. Majority of patients with steroid-resistant nephrotic syndrome were also resistant to mycophenolate mofetil and CsA. Conclusion: There was a high prevalence of minimal change disease based on kidney biopsy especially in boys younger than six years of age and response to steroid and CsA was almost similar.

  14. Clinical predictors of aggressive/disabling disease: ulcerative colitis and crohn disease.

    Science.gov (United States)

    Blonski, Wojciech; Buchner, Anna M; Lichtenstein, Gary R

    2012-06-01

    Many clinical factors predict the aggressive course of CD. Younger age at initial diagnosis, the presence of perianal lesions, ileal involvement, smoking, and the need for therapy with corticosteroids are the major predictors of disabling disease or change of behavior to a more aggressive disease. On the other hand, treatment with azathioprine and biologic agents and colonic localization of disease are the major factors that are predictive of less aggressive CD course. The problem we face with determining the factors that increase the risk of disabling disease is that there is no standardized and consistent definition of disabling or aggressive disease. Only two studies analyzed predictors using the same definition of aggressive disease. Only Beaugerie and colleagues developed the score predictive of disabling disease based on three independent factors associated with disabling course that were present at the time of initial diagnosis of CD (requirement of corticosteroids, age less than 40 years, and presence of perianal disease). This score ranged from 0 to 3 points based on the presence of given parameters. The positive predictive value was 0.91 and 0.93 in patients having two or three risk factors, 0.61 for no factors present, and 0.67 for one factor present. In order to determine factors predictive of disabling CD there is a need to establish consistent definition of disabling disease with subsequent future studies on large group of patients to validate such definition and determine factors that may predict the aggressive course.

  15. Long-term Outcomes and Risk Factors for Reoperation After Surgical Treatment for Gastrointestinal Crohn Disease According to Anti-tumor Necrosis Factor-α Antibody Use: 35 Years of Experience at a Single Institute in Korea.

    Science.gov (United States)

    Lee, Sang Mok; Han, Eon Chul; Ryoo, Seung-Bum; Oh, Heung-Kwon; Choe, Eun Kyung; Moon, Sang Hui; Kim, Joo Sung; Jung, Hyun Chae; Park, Kyu Joo

    2015-08-01

    Crohn disease is characterized by high rates of recurrence and reoperations. However, few studies have investigated long-term surgical outcomes in Asian populations. We investigated risk factors for reoperation, particularly those associated with anti-tumor necrosis factor-α (anti-TNF-α) antibody use, and long-term follow-up results. We reviewed the records of 148 patients (100 males and 48 females) who underwent surgery for gastrointestinal Crohn disease and retrospectively analyzed long-term outcomes and risk factors. The mean age at diagnosis was 28.8 years. Thirty-eight patients (25.7%) received monoclonal antibody treatment before reoperation. A small bowel and colon resection was most commonly performed (83 patients, 56.1%). The median follow-up was 149 months, during which 47 patients underwent reoperation. The median interval between the primary and the secondary surgeries was 65 months, with accumulated reoperation rates of 16.5%, 31.8%, and 57.2% after 5, 10, and 15 years, respectively. Obstruction was the most common indication for reoperation (37 patients, 25.0%). In a multivariable analysis, age Crohn diseases. Younger age at primary operation, penetrating behavior, and no azathioprine use were significant factors associated with reoperation for gastrointestinal Crohn disease.

  16. Leukopenia predicts remission in patients with inflammatory bowel disease and Behcet's disease on thiopurine maintenance.

    Science.gov (United States)

    Park, Mi Sung; Kim, Dong Hyun; Kim, Duk Hwan; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2015-01-01

    The thiopurine drugs, azathioprine (AZA), and 6-mercaptopurine (6-MP) are well-established drugs for the treatment of inflammatory bowel disease (IBD). Although leukopenia is a well-recognized side effect of AZA/6-MP treatment, its association with therapeutic effects has yet to be determined. We therefore evaluated the influences of thiopurine-induced leukopenia on the long-term prognosis of IBD. We included 196 IBD patients [45 with ulcerative colitis (UC), 68 with Crohn's disease (CD), and 83 with intestinal Behçet's disease (BD)] who were treated with AZA/6-MP and achieved remission between January 2006 and December 2012. We retrospectively analyzed patient characteristics, AZA/6-MP maintenance dose (mg/kg), the lowest white blood cell (WBC) count during AZA/6-MP treatment, duration of remission, and the occurrence of relapse. We compared the clinical variables between leukopenic (n = 120, WBC count leukopenia were negatively associated with relapse (odds ratios 0.975, 0.988, 0.563, and 0.390, respectively). On subgroup analysis, the cumulative relapse-free survival rate was significantly higher in the leukopenic group than in the nonleukopenic group for all types of IBDs, including UC, CD, and intestinal BD (log-rank test, P = 0.032, 0.047, and 0.002, respectively). Leukopenia during thiopurine maintenance therapy was associated with prolonged remission in patients with IBD and Behcet's disease.

  17. Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leukopenia in the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ding, Liang; Zhang, Fang-bin; Liu, Hui; Gao, Xiang; Bi, Hui-chang; Wang, Xue-ding; Chen, Bai-li; Zhang, Yu; Zhao, Li-zi; Zhong, Guo-ping; Hu, Pin-jin; Chen, Min-hu; Huang, Ming

    2012-01-01

    Thiopurine drugs are widely used in the treatment of inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S-methyltransferase (TPMT) is of importance for thiopurine metabolism and adverse events occurrence. The role of other thiopurine-metabolizing enzymes is less well known. This study investigated the effects of TPMT and hypoxanthine guanine phosphoribosyltransferase (HPRT) activities on 6-thioguanine nucleotides (6-TGNs) concentrations and thiopurine-induced leukopenia in patients with IBD. Clinical data and blood samples were collected from 120 IBD patients who were receiving azathioprine (AZA)/6-mercaptopurine (6-MP) therapy. Erythrocyte TPMT, HPRT activities and 6-TGNs concentrations were determined. HPRT activity and its correlation with TPMT activity, 6-TGNs level, and leukopenia were evaluated. The HPRT activity of all patients ranged from 1.63-3.33 (2.31 ± 0.36) μmol/min per g Hb. HPRT activity was significantly higher in patients with leukopenia (27, 22.5%) than without (P leukopenia (r = 0.526, P = 0.005). Patients with HPRT activity > 2.70 μmol/min per g Hb could have an increased risk of developing leukopenia (odds ratio = 7.47, P leukopenia. High levels of HPRT activity could be a predictor of leukopenia and unsafe 6-TGN concentrations in patients undergoing AZA/6-MP therapy. This could partly explain the therapeutic response or toxicity that could not be adequately explained by the polymorphisms of TPMT. Copyright © 2011 Crohn's & Crohn's & Colitis Foundation of America, Inc.

  18. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Ramya Chockalingam

    2015-06-01

    Full Text Available Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed.

  19. [Cardiac transplantation and neoplasms: experiences at Escola Paulista de Medicina of the Federal University of São Paulo].

    Science.gov (United States)

    Mello Junior, Walter Teixeira de; Branco, João Nelson R; Catani, Roberto; Aguiar, Luciano de Figueiredo; Paez, Rodrigo Pereira; Buffolo, Enio

    2006-02-01

    To study the occurrence and types of neoplasms developed by patients who underwent an orthotopic cardiac transplantation under the Program of Cardiac Transplantation of Escola Paulista de Medicina, Federal University of São Paulo. This is an observational study of 106 patients who underwent orthotopic cardiac transplantation from November 1986 to September 2002 and survived at least thirty days following the procedure. The triple immunosuppressive regimen given included cyclosporin A, azathioprine and a corticosteroid agent. Only two patients received OKT3 in addition to the regimen established. Mean follow-up was 61.4 months (ranging from two months to 192 months). Twenty-three patients (21.3%) developed neoplasms--56.5% of these were skin neoplasm, 30.1%, solid tumors, and 13.4% of post-transplant lymphoproliferative disease (PTLD). Mean interval between transplantation and diagnosis of neoplasm was: 54.9 months for skin neoplasm; 24.8 months for solid tumors and 70.3 months for PTLD. Malignant neoplasms are relatively common in the population studied. Skin cancer was the most common type compared to the other types of neoplasms. Solid tumors were more frequently diagnosed than the lymphoproliferative diseases in the population examined.

  20. A case of vesicular cutaneous lupus erythematosus in a Border collie successfully treated with topical tacrolimus and nicotinamide-tetracycline.

    Science.gov (United States)

    Lehner, Georg M; Linek, Monika

    2013-12-01

    Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period. © 2013 ESVD and ACVD.

  1. The Use of Immunosuppressant Therapy for Multiple Sclerosis in Italy: A Multicenter Retroprospective Study.

    Directory of Open Access Journals (Sweden)

    Emanuele D'Amico

    Full Text Available Immunosuppressive agents (ISA have been used in multiple sclerosis (MS for decades, frequently as off label licensed therapies. Given the new MS treatment landscape, what place do ISA have in combating MS?We conducted a retrospective multicentre study to investigate the frequency of ISA prescription in 17 Italian MS centres, and to describe the clinical factors related to ISA use.Out of 6,447 MS patients, 2,034 (31.6% were treated with ISA, with Azathioprine being the most frequently used ISA overall. MS patients treated with ISA alone were more frequently affected by the progressive course (both primary and secondary of the disease (RRR 5.82, 95% CI 4.14-8.16, p<0.0001, had higher EDSS (RRR 3.69, 95% CI 2.61-5.21, p<0.0001, higher assignment age (RRR 1.04, 95% CI 1.03-1.06, p<0.0001 than patients treated with only disease modifying drugs (DMDs.Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population.

  2. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  3. Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab.

    Science.gov (United States)

    Popler, Jonathan; Alimohammadi, Mohammad; Kämpe, Olle; Dalin, Frida; Dishop, Megan K; Barker, Jennifer M; Moriarty-Kelsey, Margaret; Soep, Jennifer B; Deterding, Robin R

    2012-01-01

    Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1 patients, significant pulmonary disease is observed. Autoantibodies directed against the potassium channel regulatory protein (KCNRG), found in epithelial cells of terminal bronchioles, have been suggested as a marker for pulmonary disease in APS-1 patients. We report two patients with APS-1; one with and one without lung disease. Patient 1 had multiple admissions for pneumonia and respiratory insufficiency, required non-invasive ventilation, and had findings of bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS-1 patients, both were tested in a blinded manner for the presence of autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies present. Additionally, Patient 1 had progressive disease despite treatment with several immunomodulating agents, including corticosteroids, azathioprine, and mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good response. This report illustrates the practical use of KCNRG autoantibodies to identify APS-1 patients with pulmonary risk and the successful use of the monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients. Copyright © 2011 Wiley Periodicals, Inc.

  4. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Field, E.H.; Strober, S.; Hoppe, R.T.

    1983-01-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values

  5. Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus: a case report.

    Science.gov (United States)

    Danve, Abhijeet; Perry, Lisa; Deodhar, Atul

    2014-10-01

    Pregnancy can lead to flares in systemic lupus erythematosus (SLE), and the presence of SLE in pregnancy could lead to a poor outcome for the mother and the fetus. To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy. A case report and review of relevant literature is presented. A 38-year-old Caucasian woman with SLE was seen for advice regarding planning a pregnancy and management of her active lupus (cutaneous lupus, angioedema, lupus nephritis, leukopenia, and anti-phospholipid antibody syndrome) that could only be controlled by mycophenolate, a drug contraindicated in pregnancy. Azathioprine, hydroxychloroquine, rituximab, and moderate doses of prednisone were either unable to control her disease or led to unacceptable toxicity. After detailed discussions, she was treated with belimumab, which controlled her SLE and allowed withdrawal of mycophenolate. Belimumab was continued throughout the pregnancy, leading to well-controlled SLE and uneventful course, albeit with the presence of mild Ebstein's anomaly in the baby. To our knowledge, this is the first case report of belimumab use throughout pregnancy for controlling active SLE. Data from the belimumab pregnancy registry would be useful to confirm our findings and to further assess safety of this agent for use in pregnancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Systemic lupus erythematosus and pregnancy outcomes: an update and review of the literature.

    Science.gov (United States)

    Peart, Erica; Clowse, Megan E B

    2014-03-01

    This review synthesizes new data from the studies published between 2011 and 2013, with particular focus on the different information gleaned by various study types. Population-based cohorts have demonstrated that women with systemic lupus erythematosus (SLE) have fewer live births and more pregnancy complications, but can have successful live births after having a poor outcome. A retrospective study suggests that only 4 months, not the traditional 6 months of disease quiescent SLE prior to pregnancy improves outcomes. Prospective studies identified several novel predictors of poor pregnancy outcomes, including uterine Doppler and laboratory findings. A prospective study found great success in transitioning to azathioprine from mycophenolate mofetil prior to pregnancy in patients with quiet lupus nephritis. Two retrospective analyses suggest that hydroxychloroquine may prevent congenital heart block in pregnancies exposed to SSA/Ro antibodies. Finally, the initial pregnancy data for belimumab suggest a high degree of transplacental transfer, but thus far no definitive link between belimumab and congenital abnormalities. Recent studies suggest both novel markers of poor pregnancy outcomes and new approaches to the management of lupus during pregnancy.

  7. Risk factors of systemic lupus erythematosus flares during pregnancy.

    Science.gov (United States)

    Jara, Luis J; Medina, Gabriela; Cruz-Dominguez, Pilar; Navarro, Carmen; Vera-Lastra, Olga; Saavedra, Miguel A

    2014-12-01

    This review examines the risk factors for the development of systemic lupus erythematosus (SLE) flares during pregnancy. In preconception, anti-DNA, hypocomplementemia, previous thrombosis, triple antiphospholipid (aPL) antibody positivity, active lupus nephritis and discontinuation of medications such as hydroxychloroquine and azathioprine are factors associated with pregnancy failure. During pregnancy, SLE flares are associated with aPL antibodies, synergic changes of pregnancy on Th1 and TH2 cytokines, other cytokines and chemokines that interact with hormones such as estrogen and prolactin that amplify the inflammatory effect. From the clinical point of view, SLE activity at pregnancy onset, thrombocytopenia, lupus nephritis, arterial hypertension, aPL syndromes, preeclampsia is associated with lupus flares and fetal complications. In puerperium, the risk factors of flares are similar to pregnancy. Hyperactivity of immune system, autoantibodies, hyperprolactinemia, active lupus nephritis, decrease in TH2 cytokines with increase in TH1 cytokines probably participate in SLE flare. The SLE flares during pregnancy make the difference between an uncomplicated pregnancy and pregnancy with maternal and fetal complications. Therefore, the knowledge of risk factors leads the best treatment strategies to reduce flares and fetal complications in SLE patients.

  8. Pemphigus: Our Clinical Experiences and Treatment Alternatives in the Resistant Cases

    Directory of Open Access Journals (Sweden)

    Soner Uzun

    2008-08-01

    Full Text Available Pemphigus is an autoimmune blistering disease affecting skin and mucous membranes which threatens the life. In our country it is the most common disease in this group. In our region, among the pemphigus cases, the most common variant is pemphigus vulgaris. Pemphigus vulgaris consists of the 80% of pemphigus cases and it occurs 10 times more than pemphigus foliaceus. Treatment of pemphigus is accepted as a miracle in clinical medicine. The disease, which had an almost always fatal outcome, had been turned to the disease which long-term remissions or “cure” can be achievable. However, in the past the cause of the death was the disease itself, nowadays, with decreasing frequency, all of the mortalities is due to the treatment side effects. In treatment of pemphigus which drug to use and when to use it has varieties according to the intended effect. Corticosteroids are the main treatment; besides IVIg, plasmapheresis or pulse steroid prefers to control the disease rapidly. Mainly immunosuppressive agents (azathioprine, methotrexate, cyclophosphamide, cyclosporine, and mycophenolate besides gold, dapsone, antibiotics or rituximab are using for late-term effect and to reduce the corticosteroid requirement.

  9. Dapsone for immune thrombocytopenic purpura in children and adults.

    Science.gov (United States)

    Patel, Ashwin P; Patil, Amit S

    2015-01-01

    Dapsone is one of the second line treatments of immune thrombocytopenic purpura (ITP). Dapsone is cheap and has response rates comparable to other second line treatment options like azathioprine, danazol, cyclophosphamide, cyclosporine, and vincristine. This retrospective analysis includes 38 patients (out of total 313 patients) of ITP treated with dapsone from 2004 to 2012. All male patients were screened for G6PD deficiency before starting dapsone. Out of 38 patients (12 children and 26 adults), one was newly diagnosed ITP, seven were persistent ITP, and 30 were chronic ITP. Five patients had side effects of dapsone; two required discontinuation due to skin rashes. The average dose of dapsone was 1.57 mg/kg/day and time to response was 57 days (19-108 days). The response was irrespective of previous treatments and response to them. The response rate was 48.6% (complete response = 40.5%). Only two adult patients had sustained response (> 6 months) after dapsone discontinuation. There were no predictors identified for dapsone response. Dapsone is a safe and cheap second-line therapy for ITP with a response rate of about 50% (majority being CR). A response to dapsone is slow, sustained, and relapses are uncommon on therapy. Dapsone withdrawal leads to relapse in most of the patients.

  10. Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review

    Science.gov (United States)

    Salama, Abdulgabar

    2015-01-01

    Summary Until now, treatment of primary autoimmune hemolytic anemia of the warm type (wAIHA) is primarily based on immunosuppression. However, many patients do not respond adequately to treatment, and treated patients may develop severe side effects due to uncontrolled, mixed and/or long-lasting immunosuppression. Unfortunately, the newly used therapeutic monoclonal antibodies are unspecific and remain frequently ineffective. Thus, development of a specific therapy for AIHA is necessary. The ideal therapy would be the identification and elimination of the causative origin of autoimmunization and/or the correction or reprogramming of the dysregulated immune components. Blood transfusion is the most rapidly effective measure for patients who develop or may develop hypoxic anemia. Although some effort has been made to guide physicians on how to adequately treat patients with AIHA, a number of individual aspects should be considered prior to treatment. Based on my serological and clinical experience and the analysis of evidence-based studies, we remain far from any optimized therapeutic measures for all AIHA patients. Today, the old standard therapy using controlled steroid administration, with or without azathioprine or cyclophosphamide, is, when complemented with erythropoiesis-stimulating agents, still the most effective therapy in wAIHA. Rituximab or other monoclonal antibodies may be used instead of splenectomy in therapy-refractory patients. PMID:26696797

  11. An unusual association between hemophagocytic lymphohistiocytosis, mixed connective tissue disease, and autoimmune hemolytic anemia: A case report.

    Science.gov (United States)

    Kelkar, Amar H; Shah, Anushi A; Yong, Sherri L; Ahmed, Zohair

    2017-07-01

    In the adult patient, hemophagocytic lymphohistiocytosis (HLH) is uncommon and frequently difficult to diagnose due to its nonspecific presentation and numerous complications. Herein, we present the case of a 25-year-old female who initially presented for evaluation of persistent fevers and fatigue. She was found to have splenomegaly, generalized lymphadenopathy, pancytopenia, and acute hepatic failure. Her course was further complicated by the development of nephrotic syndrome and autoimmune hemolytic anemia (AIHA). Antinuclear antibody and ribonucleoprotein were positive, with concurrent physical examination findings, indicating underlying mixed connective tissue disease (MCTD). Ferritin was greater than 40,000 ng/dL. Viral studies, including hepatitis A, B, and C, cytomegalovirus, and Epstein-Barr virus were negative. On the basis of her clinical presentation, a diagnosis of HLH secondary to MCTD was made. This was later confirmed on liver biopsy. She was started on high-dose prednisone and her symptoms completely resolved. She was then transitioned to azathioprine, hydroxychloroquine, prophylactic antibiotics, and a prednisone taper for long-term management. This case is notable for the association of both AIHA and MCTD with HLH, providing support for a possible relationship between these 3 conditions.

  12. HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants.

    Science.gov (United States)

    Heap, Graham A; Weedon, Michael N; Bewshea, Claire M; Singh, Abhey; Chen, Mian; Satchwell, Jack B; Vivian, Julian P; So, Kenji; Dubois, Patrick C; Andrews, Jane M; Annese, Vito; Bampton, Peter; Barnardo, Martin; Bell, Sally; Cole, Andy; Connor, Susan J; Creed, Tom; Cummings, Fraser R; D'Amato, Mauro; Daneshmend, Tawfique K; Fedorak, Richard N; Florin, Timothy H; Gaya, Daniel R; Greig, Emma; Halfvarson, Jonas; Hart, Alisa; Irving, Peter M; Jones, Gareth; Karban, Amir; Lawrance, Ian C; Lee, James C; Lees, Charlie; Lev-Tzion, Raffi; Lindsay, James O; Mansfield, John; Mawdsley, Joel; Mazhar, Zia; Parkes, Miles; Parnell, Kirstie; Orchard, Timothy R; Radford-Smith, Graham; Russell, Richard K; Reffitt, David; Satsangi, Jack; Silverberg, Mark S; Sturniolo, Giacomo C; Tremelling, Mark; Tsianos, Epameinondas V; van Heel, David A; Walsh, Alissa; Watermeyer, Gill; Weersma, Rinse K; Zeissig, Sebastian; Rossjohn, Jamie; Holden, Arthur L; Ahmad, Tariq

    2014-10-01

    Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.

  13. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation

    International Nuclear Information System (INIS)

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.L.

    1982-01-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or tertiary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  14. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

  15. Approach to patients with refractory coeliac disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ikram Nasr

    2016-10-01

    Full Text Available Refractory coeliac disease (RCD is a recognised complication, albeit very rare, of coeliac disease (CD. This condition is described when individuals with CD continue to experience enteropathy and subsequent or ongoing malabsorption despite strict adherence to a diet devoid of gluten for at least 12 months and when all other causes mimicking this condition are excluded. Depending on the T-cell morphology and T-cell receptor (TCR clonality at the β/γ loci, RCD can be subdivided into type 1 (normal intra-epithelial lymphocyte morphology, polyclonal TCR population and type 2 (aberrant IELs with clonal TCR. It is important to differentiate between the two types as type 1 has an 80% survival rate and is managed with strict nutritional and pharmacological management. RCD type 2 on the other hand has a 5-year mortality of 50% and can be complicated by ulcerative jejunitis or enteropathy-associated T-cell lymphoma (EATL. Management of RCD type 2 has challenged many experts, and different treatment approaches have been adopted with variable results. Some of these treatments include immunomodulation with azathioprine and steroids, methotrexate, cyclosporine, alemtuzumab (an anti CD-52 monoclonal antibody, and cladribine or fludarabine sometimes with autologous stem cell transplantation. In this article, we summarise the management approach to patients with RCD type 2.

  16. Refractory Celiac Disease

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    K Khatami

    2014-04-01

    Full Text Available Refractory celiac disease (RCD is when malabsorption symptoms and villous atrophy persist despite strict adherence to a gluten free diet (GFD for more than 12 months and other causes of villous atrophy have been ruled out.  RCD is considered a rare disease and almost exclusively occurs in adults. Persistent diarrhea, abdominal pain, weight loss are the most common symptoms in RCD. Also, anemia, fatigue, malaise, thromboembolic events and coexisting autoimmune disorders are frequent. Diagnosis of RCD is based on other causes of unresponsiveness to the GFD, particularly collagenous sprue, ulcerative jejunitis, and enteropathy-associated T-cell lymphoma. Many disorders such as autoimmune enteropathy, tropical sprue, common variable immunodeficiency, and intolerance to non-gluten dietary proteins may have similar histological findings but not necessarily identical with CD and therefore should be excluded. Repeat intestinal biopsy may help to differentiate causes of non-responsive CD associated with ongoing villous atrophy (e.g., gluten contamination, small-bowel bacterial overgrowth, RCD. There are 2 subtypes of RCD according to absence (type I or presence (type II of an abnormal intraepithelial lymphocyte population. RCD type 1 usually becomes better with a combination of aggressive nutritional support, adherence to GFD, and pharmacologic therapies such as prednisone, budesonide and azathioprine. For RCD type 2, more aggressive therapeutic approach is needed since clinical response to therapies is less certain and may evolve into aggressive enteropathy associated T-cell lymphoma and the prognosis is poor.   Key words: Celiac Disease, Refractory.  

  17. Granulomatosis with polyangiitis (Wegener's disease): An updated review of ocular disease manifestations

    Science.gov (United States)

    Kubaisi, Buraa; Abu Samra, Khawla; Foster, C. Stephen

    2016-01-01

    Summary Granulomatosis with polyangiitis (GPA) is a potentially lethal systemic disorder that is characterized by necrotizing vasculitis of small arteries and veins. The respiratory system is most commonly affected in limited forms of the disease, however upper and lower respiratory system, systemic vasculitis, and necrotizing glomerulonephritis are the characteristic components of the disease triad. The peak incidence is observed at 64–75 years of age, with a prevalence of 8–10 per million depending on geographic location. In this review we focus on the ocular manifestations of the disease which occur in nearly in one third of the patients. In addition we describe the neuro-ophthalmic complications which occur in up to half of cases. We also discuss the current systemic treatment options including corticosteroids, cyclophosphamide, azathioprine, and the available biologic response modifiers including rituximab. The disease remains difficult to diagnose due to the generalized symptomatic presentation of patients with GPA. As a result, several sets of diagnostic criteria have been developed which include clinical, serological, and histopathological findings to varying extents. Early diagnosis and multi-specialty collaboration among physicians is necessary to adequately manage the disease and the potential complications that may result from drugs used in the treatment of the disease. Despite recent advances, more research is necessary to prevent the high rates of mortality from the disease itself and from therapeutic side effects. PMID:27195187

  18. Atualização do tratamento das vasculites associadas a anticorpo anticitoplasma de neutrófilos Treatment of antineutrophil cytoplasmic antibody-associated vasculitis: update

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    Alfredo Nicodemos Cruz Santana

    2011-12-01

    Full Text Available As vasculites antineutrophil cytoplasmic antibody (ANCA, anticorpo anticitoplasma de neutrófilos associadas (VAAs são caracterizadas por uma inflamação sistêmica das artérias de pequeno e médio calibre (especialmente no trato respiratório superior e inferior, e nos rins. As VAAs compreendem a granulomatose de Wegener (agora chamada de granulomatose com poliangeíte, poliangeíte microscópica, VAA limitada ao rim e a síndrome de Churg-Strauss. Neste artigo, discutiremos as fases de tratamento dessas vasculites, como fase de indução (com ciclofosfamida ou rituximab e fase de manutenção (com azatioprina, metotrexato ou rituximab. Além disso, discutiremos como manusear os casos refratários à ciclofosfamida.In its various forms, antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV is characterized by a systemic inflammation of the small and medium-sized arteries (especially in the upper and lower respiratory tracts, as well as in the kidneys. The forms of AAV comprise Wegener's granulomatosis (now called granulomatosis with polyangiitis, microscopic polyangiitis, renal AAV, and Churg-Strauss syndrome. In this paper, we discuss the phases of AAV treatment, including the induction phase (with cyclophosphamide or rituximab and the maintenance phase (with azathioprine, methotrexate, or rituximab. We also discuss how to handle patients who are refractory to cyclophosphamide.

  19. External dacryocystorhinostomy surgery in patients with Wegener granulomatosis.

    Science.gov (United States)

    Lee, Brian J; Nelson, Christine C; Lewis, Craig D; Perry, Julian D

    2012-01-01

    To determine surgical outcomes after external dacryocystorhinostomy (DCR) surgery in patients with Wegener granulomatosis (WG). The authors retrospectively reviewed the charts of consecutive patients with WG who underwent primary or secondary external DCR surgery between January 2001 and January 2010. Clinical data reviewed included patient demographics, systemic disease involvement and immunosuppression therapy, intraoperative biopsy findings, and postoperative outcomes and complications. Success was defined as resolution of epiphora. Sixteen primary external DCRs were performed on 9 patients with WG, and 2 secondary external DCRs were performed on 2 patients. At the time of surgery, all patients with WG were on systemic immunosuppressive agents including methotrexate, rapamycin, sirolimus, tacrolimus, azathioprine, cyclophosphamide, rituximab, and prednisone, and no patients received increased corticosteroids after surgery. Intraoperative biopsy in patients with WG revealed chronic inflammation (4 patients) and fibrosis (1 patient). Silicone stents were removed at an average of 5.8 months (range, 3-12 months). All surgeries were successful in resolving epiphora with an average follow up of 3.5 years (range, 10 months-6 years) and no complications. Primary and secondary external DCR surgery successfully treats nasolacrimal duct obstruction in patients with WG on systemic immunosuppression.

  20. Clinical features and outcomes of ANCA-associated renal vasculitis

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    Sidy Mohamed Seck

    2012-01-01

    Full Text Available To determine the patterns and outcomes of the pauci-immune vasculitis in the nephrology department at hospital La Conception in Marseille, we conducted a retrospective study including all patients with diagnosis of pauci-immune renal vasculitis between January 1, 2000 and December 31, 2007. Among 33 cases, 25 were diagnosed as Wegener granulomatosis (WG, seven as microscopic polyangitis (MPA and one as Churg-Strauss syndrome (SCS. The median age of the patients was 57.7 years and the sex-ratio (M/F was 1.6. The visceral mani-festations included kidneys (100% of patients, lungs (75%, ENT (52% of WG, and nervous system (57% of MPA. The mean serum creatinine at admission was 3.3 mg/dL. Renal biopsies revealed a pauci-immune crescentic gromerulonephritis in 96% of the cases. Two patients with WG received plasmapheresis and seven patients required emergency hemodialysis. Induction therapy comprised cyclophosphamide IV and corticosteroids, while maintenance therapy included azathioprine for the majority of patients. Eighty four percent of the patients experienced complete remission after induction therapy. During maintenance therapy relapses were more frequent among patients with MPA (28% compared to WG cases (12%. After 35 months of follow-up, eight patients ended on chronic hemodialysis, and five patients died. ANCA associated vasculitis are frequent in our patients. Long-term outcomes are relatively good despite a mortality rate of 15% and 25% of the patients entering dialysis after three years of follow-up.

  1. Granulomatosis With Polyangiitis in Otolaryngologist Practice: A Review of Current Knowledge.

    Science.gov (United States)

    Wojciechowska, Joanna; Krajewski, Wojciech; Krajewski, Piotr; Kręcicki, Tomasz

    2016-03-01

    Granulomatosis with polyangiitis (GPA) is an idiopathic vasculitis of medium and small arteries, characterized by necrotizing granulomatous inflammation. GPA typically affects upper and lower respiratory tract with coexisting glomerulonephritis. This disease is generally characterized by antineutrophil cytoplasm antibodies (ANCA), nevertheless, there are rare cases with negative ANCA. GPA affects people at any age, with predominance of the sixth and seventh decade of life. In 80%-95% of the patients the first symptoms of GPA are otorhinolaryngological manifestations of head and neck including nose/sinuses, ears, eyes, larynx/trachea, oral cavity, and salivary glands. Diagnosis of GPA is based on Criteria of the American College of Rheumatology. In clinical practice diagnosis, the presence of distinctive ANCA antibodies and biopsy of affected organ are crucial. GPA must be differentiated from neoplastic, infectious or inflammatory ulcerative lesions of the head and neck. The standard treatment procedure is divided into two essential phases, induction and maintenance. The induction phase is based on combination of systemic corticosteroid and immunosuppressant therapy, whereas the maintenance phase comprises corticosteroids and azathioprine/methotrexate supplementation. Surgical treatment ought to be considered for patients who are not responding to pharmacotherapy.

  2. The southern region renal transplant program at armed forces hospital, khamis mushayt.

    Science.gov (United States)

    Mohammed, A S; Al-Hashemy, A; Addous, A J; Ismail, G

    1996-01-01

    The Southern Region renal transplant program was established in February 1989. The appointment of a transplant co-ordinator and creation of a waiting list for the Southern Region as well as tissue typing of all patients in the region were important early steps. Between February 1989 and December 1995, 155 transplants were performed on 152 patients at the Armed Forces Hospital, Southern Region (AFHSR). Of them, 52 were cadaveric donor transplants and the remaining were from living related donors. The overall five-year actuarial patient and graft survival was 93% and 78% respectively. Of the 152 patients who were transplanted, 79 patients were from other hospitals in the region and 73 were from AFHSR. Maintenance immunosuppression consisted of cyclosporin, azathioprine and prednisolone. Use of the spouse as a donor was an early feature of this program. Our results compare favorably with results published from other centers. To cope with the increasing demand of transplantation in the Southern Region, we have to look into ways of increasing our transplant numbers to match the needs.

  3. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies

    International Nuclear Information System (INIS)

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.S.

    1982-01-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  4. Pregnancy in Women With Solid-Organ Transplants: A Review.

    Science.gov (United States)

    Durst, Jennifer K; Rampersad, Roxane M

    2015-06-01

    Advances in solid-organ transplantation have allowed many women to reach reproductive potential, and pregnancy is no longer a rarity for these women. To identify (1) potential complications to allograft function posed by pregnancy, (2) expected perinatal outcomes in women with solid-organ transplants, (3) risks of potential immunosuppressant regimens, (4) safety of lactation, and (5) contraceptive options for women with solid-organ transplants. Single-center, registry data, and previous systematic reviews were evaluated in women with solid-organ transplants to identify the objectives of this review. In addition, recommendations from public health organizations were examined in regard to safety of medications and contraceptive methods. Women with solid-organ transplants are at risk for premature birth, low birth weight, cesarean delivery, and hypertensive disorders of pregnancy. Most immunosuppressant regimens are safe; however, mycophenolate mofetil should be avoided. Lactation with tacrolimus, cyclosporine, azathioprine, and prednisone appears safe. Long-acting reversible contraceptive methods are safe and effective for transplant recipients. Many successful pregnancies have been achieved in women following transplantation; however, optimal perinatal outcomes require stable allograft function. As more women are becoming pregnant after organ transplantation, a review of obstetric recommendations and perinatal outcome is warranted.

  5. The effects of immune modulation on plutonium dioxide lung carcinogenesis in the rat

    International Nuclear Information System (INIS)

    Nolibe, D.; Discour, M.; Masse, R.; Lafuma, J.

    1979-01-01

    After inhalation of radioactive particles only some rats developed lung tumors. It was interesting to see whether this was a random effect or the result of different individual susceptibilities. Among the possible individual differences, cell mediated mechanisms and genetic factors have been reported. The relationships between cancerogenesis and host immune status are tested on rats submitted to an inhalation of plutonium dioxide particles after depression by azathioprine, hydrocortisone or thymectomy. The effects of immuno stimulation by BCG are also studied. The influence of genetic factors is studied with the same protocol on two strains of Wistar rats outbred or inbred. The incidence, nature, size, extension and metastases of tumors are compared between the groups. Results give a good evidence that AZA treated rats and thymectomized rats have a greater incidence of spontaneous tumors. This effect is observed at different levels in the two strains of rats. According to strain used, immunodepression have no or weak enhancing effect on PuO 2 tumor induction, but significant effect of development of tumors is always observed. A shift towards bronchogenic type is also observed. BCG have also an enhancing effect on development of tumors and no protective effect on their incidence

  6. Pyoderma gangrenosum: A commonly overlooked ulcerative condition

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    Daniel Zunsheng Tay

    2014-01-01

    Full Text Available Background: Pyoderma ga ngrenosum (PG is a rare, inflammatory, destructive neutrophilic dermatosis, which mimics other ulcerative conditions. Materials and Methods: In a retrospective study based on patients diagnosed with PG over a 3-year period (2010-2013, we evaluated demographics, anatomical sites, number of lesions, subtypes, histopathology, associated conditions, treatment regimens, healing time, and recurrence. Results: Of our five patients, there were three males and two females, age ranging between 19 and 58 years (mean age 38 years. Four had single lesions localized to the lower limbs while one had multiple lesions (more than five over bilateral hands and legs. Ulcerative subtype was observed in all the patients. One exhibited pathergy. Skin biopsies were done in four patients, revealing dense neutrophilic infiltrates in three cases and leukocytoclastic vasculitis in one. Associated systemic diseases were observed in all patients, four having inflammatory bowel disease and one having both systemic lupus erythematosus and anti-phospholipid syndrome. The patients were all treated with systemic corticosteroids either alone or in combination with immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus, and wound dressing. Split-thickness skin graft was done in one patient. Complete healing was achieved in all patients, ranging from one to 3 months after diagnosis. No recurrence was reported. Conclusions: Systemic corticosteroids, either alone or in combination with steroid-sparing agents are the mainstay of treatment. Should family physicians encounter a rapidly progressing ulcer that has poor response to usual wound management, timely referral to dermatology should be made.

  7. An update on medical management on Crohn's disease.

    Science.gov (United States)

    Affronti, Andrea; Orlando, Ambrogio; Cottone, Mario

    2015-01-01

    The management of Crohn's disease (CD) is continuously evolving. New issues emerging from more recent studies could influence the decision-making process in clinical practice. The aim of this review article is to highlight critical issues on the management of CD, new evidence from clinical trials, long-term prospective studies and real life experience, beyond the current guidelines. The role of mucosal healing in clinical practice is uncertain, clinical remission remains the primary end point. The timing for the definition of steroid-resistant CD should be considered between 2 and 4 weeks. Early treatment strategy with immunomodulators is effective for inducing remission but no controlled data are available regarding long-term outcome. Combination therapy (anti-TNFs agents and immunosuppressors) is more effective than single therapy but there is a lack of long-term data and an increased risk of malignancy. The effect of mesalazine, metronidazole and azathioprine in reducing postoperative recurrence is not clinically relevant; biologics are effective, but the duration of treatment is unknown. New drugs are under investigation in order to find exit strategy for patients who no longer respond to biologics. Combination therapy set on anti-TNF-α is until now the best option both to achieve fistula healing and avoid recurrence.

  8. Coexistence of Crohn’s Disease and Hodgkin’s Lymphoma in a Young Man with Rectorrhagia

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    Ahmad Hormati

    2017-02-01

    Full Text Available Introduction Crohn’s disease (CD is an inflammatory disease with an increasing incidence and can involve any part of the gastrointestinal tract. Most cases are seen in young adults presenting with abdominal pain and diarrhea. This condition may lead to complications such as stricture and fistula. Besides, there is an increased risk of colorectal cancer and some extraintestinal cancers in these patients, due to chronic inflammation. One of the therapeutic options for Crohn’s patients is the use of immunomodulators. Such agents can induce remission and limit the usage of steroids. According to some literature, this treatment can increase the risk of colorectal cancer as well as extraintestinal cancers, of which skin cancers and lymphoma are the most prevalent. Lymphoma can be a result of chronic inflammation or use of immunomodulators such as azathioprine and 6-mercaptopurine (6-MP. Case Presentation In this literature, we describe a young man with rectorrhagia who is diagnosed with Crohn’s disease and a coexistence of lymphoma at the time of diagnosis, without a history of immunomodulator therapy. Conclusions With attention to the increased risk of colorectal and extraintestinal cancer in Crohn’s patients, assessment for early diagnosis should be considered

  9. Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

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    Marta Sofia Mendes Oliveira

    2015-09-01

    Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

  10. Contemporary issues and future directions in autoimmune hepatitis.

    Science.gov (United States)

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2016-06-03

    Autoimmune hepatitis (AIH) is a severe life-threatening hepatopathy of unknown etiology, affecting both pediatric and adult populations, and characterised by inflammatory liver histology, circulating non-organ-specific autoantibodies, and hypergammaglobulinaemia. AIH is a very heterogeneous disease with a variety of clinical presentations, ranging from asymptomatic liver test abnormalities to acute severe hepatitis or even acute liver failure. It responds very well to immunosuppressive treatment with prednisolone with or without azathioprine. Patients who are intolerant or fail to respond to standard therapy are candidates for alternative immunosuppressive regimens, the combination of steroids with mycophenolate mofetil or calcineurin inhibitors being the most frequently reported. The pathogenesis of AIH remains not completely understood, although there is evidence that genetic predisposition, molecular mimicry and defective immunoregulatory mechanisms contribute to the autoimmune liver damage. A literature search was conducted using the key-words 'autoimmune hepatitis', 'immunogenetics', 'regulatory T-cells' and 'immunosuppression'. The aim of this review is to discuss recent breakthroughs in the understanding AIH pathogenesis, diagnosis and treatment. Expert commentary: Progress in the understanding of AIH pathogenesis is likely to contribute to the development of novel therapeutic strategies, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells.

  11. Severe glomerulonephritis complicated by coagulopathy: treatment with anticoaguland and immunosuppresive drugs.

    Science.gov (United States)

    Robson, A M; Cole, B R; Kienstra, R A; Kissane, J M; Alkjaersig, N; Fletcher, A P

    1977-06-01

    Serial determinations, using plasma fibrinogen gel chromatography as well as standard methodology, demonstrated that six children with severe glomerulonephritis, characterized on renal biopsy by glomerular necrosis and crescent formation, had persistent evidence of intravascular coagulation. Based on these observations, therapy with anticoagulants and azathicoagulants and azathioprine was instituted for one year; treatment with anticoagulants was continued for a second year. Anticoagulant therapy was initiated with heparin, followed by oral anticoagulation with phenindione and dipyridamole. In contrast to our earlier experience with similar patients, each of the present patients improved. Urinalyses returned to normal and glomerular filtration rates to near normal values in all patients at the end of the treatment period and have remained so for up to 3.9 years since treatment has been completed. Post-treatment biopsies showed remarkable improvement, with virtually no glomerulosclerosis even in patients who had had a high incidence of glomerular crescents before treatment. It is suggested that the therapeutic regimen favorably influenced the natural history of disease and that plasma fibrinogen chromatographic findings may be helpful in selecting patients likely to benefit from the use of anticoagulant therapy.

  12. Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

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    Suk Chon

    2011-02-01

    Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

  13. Pregnancy in Systemic Lupus Erythematosus Patients with Nephritis

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    Panagiotis Pateinakis

    2014-07-01

    Full Text Available Pregnancy in patients with lupus nephritis is a challenging clinical situation. Although not absolutely contraindicated, it is associated with increased risk for foetal and maternal complications, including foetal loss, preterm delivery, intrauterine growth retardation, hypertension, pre-eclampsia, nephritis flare, and, rarely, maternal death. The complication rate is further increased in the presence of antiphospholipid antibodies or the antiphospholipid syndrome. Proliferative classes of nephritis (III and IV also appear to confer excess risk for complications. Immunosuppressives such as cyclophosphamide and mycophenolate, and antihypertensives such as angiotensin-converting-enzyme (ACE inhibitors and angiotensin receptor blockers need to be stopped due to teratogenic effects. Agents like corticosteroids, azathioprine, and probably calcineurin inhibitors are considered compatible with gestation. Lupus activity needs to be assessed and carefully monitored. Thrombotic risk due to antiphospholipid antibodies, thrombotic events, or nephrosis needs to be evaluated and managed accordingly, with the use of aspirin and/or unfractioned or low molecular weight heparin. Differentiating between severe pre-eclampsia and lupus nephritis flare might require a renal biopsy, which might not always be feasible, for example after the 32nd gestational week or in a setting of uncontrolled hypertension or thrombocytopaenia. A 6-month history of quiescent disease on non-teratogenic agents seems to be associated with best chance for favourable outcomes. Pregnancy is optimally managed by a multidisciplinary team of experienced specialists, and close monitoring for disease activity during gestation; additionally, follow-up for maternal flare postpartum is also advised.

  14. Very late onset lymphoproliferative disorders occurring over 10 years post-renal transplantation: PTLD.Int. Survey.

    Science.gov (United States)

    Khedmat, Hossein; Taheri, Saeed

    2011-01-01

    Knowledge of the significance of post-transplant lymphoproliferative disorders (PTLD) that occur "very late" or more 10 years after renal transplantation is limited. thus, we analysed and compared characteristics and prognosis of the disease in renal transplant patients with very late onset PTLD vs. early- and late-onset PTLD. Retrospective study of data obtained from comprehensive search of medical literature We searched for available data using the Pubmed and Google scholar search engines for reports of lymphoproliferative disorders occurring in renal transplant patients by disease presentation time. We analyzed data from 27 studies that included 303 patients with lymphoproliferative disorders after renal transplantation. Renal graft recipients with very late onset PTLD were significantly less likely to be under mycophenolate mofetil (MMF)- and/or tacrolimus (FK-506) (vs. azathioprine) -based immunosuppression (P=.035) and less likely to have a history of antibody induction immunosuppression (P.1 for all). Older renal transplant patients are at increased risk for development of very late onset PTLD, and should be strictly followed. further multi-institutional prospective studies are needed to confirm our results.

  15. Disease duration and age influence CARD15 expression in Crohn’s disease

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    Elżbieta Poniewierka

    2016-01-01

    Full Text Available One of the susceptibility genes in Crohn’s disease (CD is CARD15. Our study examined the relationship between peripheral CARD15 expression and phenotype and duration of CD, treatment methods and inflammatory indices. Sixty patients with CD and 30 healthy volunteers as controls were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs with E.Z.N.A. Total RNA Kit (Omega Bio-tek then quantitative real-time PCR was performed on the ABI Prism 7900 HT Real-Time PCR System. CARD15 gene expression in PBMCs in CD was significantly higher than in the control group. The highest level of gene expression was found in CD patients in the fourth decade of life. The mRNA level of the CARD15 gene was higher in patients with disease duration between 12 and 60 months. A positive correlation was found between erythrocyte sedimentation rate (ESR and gene expression level. Gene expression increased with increasing level of C-reactive protein and ESR, but it was not statistically significant. CARD15 expression significantly decreased in CD patients treated with anti-TNFα agents compared to azathioprine or steroid treatment groups. Expression of the CARD15 gene in Crohn›s disease is higher than in healthy individuals. Disease duration and age of patients seem to be the most important factors influencing CARD15 expression.

  16. State of the art - how I manage immune thrombocytopenia.

    Science.gov (United States)

    Cooper, Nichola

    2017-04-01

    The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed. © 2017 John Wiley & Sons Ltd.

  17. Experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle.

    Science.gov (United States)

    Campo, M S; O'Neil, B W; Barron, R J; Jarrett, W F

    1994-08-01

    Bovine papillomavirus type 4 (BPV-4) is the aetiological agent of epithelial papillomas of the upper alimentary canal in cattle. These benign tumours can become a focus for transformation to squamous cell carcinomas in animals feeding on bracken fern. Strong epidemiological evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and mutagenic and immunosuppressing chemicals present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower intestine and bracken-grazing animals are also heavily immunosuppressed. To elucidate the individual roles and the concerted action of the viral and chemical factors involved in tumorigenesis and malignant conversion, we attempted to reproduce experimentally the cancer syndrome observed in the field. Florid persistent papillomatosis of the upper alimentary canal was reproduced in animals infected with BPV-4 and immunosuppressed either by a diet of bracken or by treatment with azathioprine; cancer of the upper alimentary tract or of the lower intestine developed only in animals infected with virus and fed on bracken fern. As in field cases, BPV-4 DNA was detected in papillomas but not in cancers. We conclude that immunosuppression is necessary for persistence and spread of viral papillomas, that the fern mutagens are responsible for neoplastic conversion of papilloma cells, and that continuous expression of viral functions is not required for the maintenance of the malignant state.

  18. Idiopathic pulmonary hemosiderosis in a 9-year-old girl.

    Science.gov (United States)

    Kamienska, E; Urasinski, T; Gawlikowska-Sroka, A; Glura, B; Pogorzelski, A

    2009-12-07

    Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening condition characterized by hemoptysis, dyspnoea, alveolar infiltrates on chest radiograph and various degrees of anemia. It may occur either as a primary disease of the lungs or a secondary condition due to cardiac, systemic vascular, collagen or renal diseases. Idiopathic pulmonary hemosiderosis (IPH) is a separate form of DAH of unknown origin, associated in some cases with celiac disease. The estimated incidence of IPH in children is 0.24-1.23 cases per million, with a mortality rate as high as 50%. Only about 500 cases of this disease have been described in medical literature. We present a case of a 9-year-old girl diagnosed with IPH, which was confirmed by the presence of many hemosiderin-laden macrophages in bronchoalveolar lavage obtained by bronchofiberoscopy. Therapy with glucocorticoids was initiated with a partial and transient response. Azathioprine and a gluten-free diet were subsequently introduced. However, the girl still suffers from recurrent episodes of hemoptysis, dyspnea and anemia.

  19. Role of oxidative stress mediated by glutathione-s-transferase in thiopurines' toxic effects.

    Science.gov (United States)

    Pelin, Marco; De Iudicibus, Sara; Fusco, Laura; Taboga, Eleonora; Pellizzari, Giulia; Lagatolla, Cristina; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana; Stocco, Gabriele

    2015-06-15

    Azathioprine (AZA), 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG) are antimetabolite drugs, widely used as immunosuppressants and anticancer agents. Despite their proven efficacy, a high incidence of toxic effects in patients during standard-dose therapy is recorded. The aim of this study is to explain, from a mechanistic point of view, the clinical evidence showing a significant role of glutathione-S-transferase (GST)-M1 genotype on AZA toxicity in inflammatory bowel disease patients. To this aim, the human nontumor IHH and HCEC cell lines were chosen as predictive models of the hepatic and intestinal tissues, respectively. AZA, but not 6-MP and 6-TG, induced a concentration-dependent superoxide anion production that seemed dependent on GSH depletion. N-Acetylcysteine reduced the AZA antiproliferative effect in both cell lines, and GST-M1 overexpression increased both superoxide anion production and cytotoxicity, especially in transfected HCEC cells. In this study, an in vitro model to study thiopurines' metabolism has been set up and helped us to demonstrate, for the first time, a clear role of GST-M1 in modulating AZA cytotoxicity, with a close dependency on superoxide anion production. These results provide the molecular basis to shed light on the clinical evidence suggesting a role of GST-M1 genotype in influencing the toxic effects of AZA treatment.

  20. The causes and clinical significance of fever in systemic lupus erythematosus: a retrospective study of 487 hospitalised patients.

    Science.gov (United States)

    Zhou, W J; Yang, Cheng-De

    2009-08-01

    The causes of fever in systemic lupus erythematosus (SLE) are complicated. Differential diagnosis of fever in SLE is crucial for optimal management of these patients. To better understand the causes and characteristics of fever in SLE, the medical records of 1949 consecutive patients hospitalised for SLE from January 2002 to May 2007 were reviewed. A total of 487 SLE-hospitalised patients with fever were identified and retrospectively analysed. Among them, 265 patients had fever from infection, 206 had fever related to SLE, 8 had fever caused by both SLE activity and infections, 4 had fever caused by malignancies and 4 had fever ascribed to miscellaneous causes. The most common sites of infection were the respiratory tract (62.6%), urinary tract (8.6%), skin and mucosa (8.3%). A prednisone dose of fever in 80.6% of the patients, usually within 1-5 days. Compared to patients with infection fever, those with SLE fever were more likely to have lower serum complement C3 and a higher SLE Disease Activity Index score. Infection fever was found to be associated with the use of azathioprine within the last six months. In conclusion, infection and disease activity are the most common causes of fever in SLE. Those patients for whom SLE fever could not be suppressed by a higher dose of steroids usually had severe lupus encephalopathy or hemophagocytic syndrome.

  1. Long-term outcomes of children after solid organ transplantation

    Directory of Open Access Journals (Sweden)

    Jon Jin Kim

    2014-01-01

    Full Text Available Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation.

  2. ANCA-negative Churg-Strauss Syndrome

    Directory of Open Access Journals (Sweden)

    Syed Jamil Abdal

    2016-08-01

    Full Text Available A rare and a disease of unknown etiology, Churg-Strauss syndrome (CSS is a granulomatous necrotizing small vessel vasculitis characterized by the presence of asthma, sinusitis, and hypereosinophilia, which is initially described by Churg and Strauss in 1951. Because of its clinical and pathological features that overlap with those of the other anti-neutrophil antibody (ANCA-associated systemic vasculitides (AASVs and now the disease is classified as AASVs. The ANCA status may dictate the clinical phenotype. ANCA-positive patients are significantly more likely to have disease manifesta­tions associated with small-vessel vasculitis, including oecrotising glomemlonephritis, mononeuritis and purpura, whereas ANCA-negative cases predominantly likely to have cardiac and lung involvement. The objective of this case report is to point out the possibility of vasculitic rash in ANCA-negative CSS in a 35-year-old man and the disease rarely occurs in Bangladeshi population. We analyze the history, clinical examinations and relevant investigations related to the patient to establish the diagnosis in our department. The clinical scenario and biopsy help us to attain the diagnosis. But due to unavailability of patients' cohort we have limitations of comparison of ANCA status in Bangladeshi populations. Though ANCA-positive and ANCA-negative CSS differ phenotypically, primary therapy for both the conditions is systemic glucocorticoids. Additional immunosuppressive agents like cyclophosphamide, mycophenolate mofetil, azathioprine, rituxin1ab are occasionally added in patients with more advanced or refractory disease.

  3. Clinical profile of patients with myasthenia gravis followed at the University Hospital, Federal University of Minas Gerais

    Directory of Open Access Journals (Sweden)

    Aline Mansueto Mourão

    2015-04-01

    Full Text Available Summary Objective: to determine the clinical profile of patients with myasthenia gravis (MG; followed at the Neuromuscular Diseases Clinic of the University Hospital, Federal University of Minas Gerais, Brazil, and to compare it with other Brazilian case series. Methods: sociodemographic and clinical data were collected from patients, and a systematic literature review performed, focusing on national studies on the clinical profile of MG patients. Results: sixty nine patients were enrolled in the study. Fifty five (91% subjects were female and the mean age (SD was 37.6 (±11.4 years. The mean disease duration was 14.1 years. Regarding treatment, prednisone was the most used strategy (64%, followed by the use of azathioprine (43%. There was no difference between thymectomized (42 and non-thymectomized (27 patients regarding disease severity and medication use. Conclusion: clinical and socio-demographic features of this MG sample from a University-based clinic resemble those reported in other Brazilian series and in the international literature.

  4. Rheumatic manifestations of inflammatory bowel disease.

    Science.gov (United States)

    Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo

    2009-11-28

    This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-alpha blocking agents should be considered as first-line therapy.

  5. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  6. Response of transplant recipients to influenza vaccination based on type of immunosuppression: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Reza Karbasi-Afshar

    2015-01-01

    Full Text Available Influenza vaccination is widely used in transplant recipients, but there is little known about the significance and correlating factors of its effectiveness. In the current study, we reviewed the existing literature on clinical trials performed in transplant recipients on the effectiveness of influenza vaccination and to evaluate the relevance of the type of immunosuppression employed in these patients on the humoral reaction to the vaccine. A comprehensive search of the literature was performed through Pubmed and Google Scholar to find reports indicating immunogenicity of influenza vaccination in transplant patients. Finally, data from 15 published clinical trials were included in the meta-analysis. Data of 947 transplant recipients retrieved from 15 clinical trials investigating the immunogenicity of influenza vaccination were analyzed in this meta-analysis. Analysis showed significantly lower rates of sero-conversion among transplant recipients receiving mycophenolate mofetil (MMF than other immunosuppressive agents (relative risk: 0.724; 95% confidence interval: 0.596-0.880; P = 0.001. No significant correlation was found with tacrolimus, sirolimus, cyclosporine and azathioprine. Different immunosuppressive agents seem to have different effects on the humoral response rate to influenza vaccination, with MMF having the most significant deleterious effect. The limited and controversial data available in the literature do not support any differential effect for other immunosuppressive agents.

  7. Myeloproliferative disorders in patients with rheumatoid arthritis treated with total body irradiation

    International Nuclear Information System (INIS)

    Urowitz, M.B.; Rider, W.D.

    1985-01-01

    Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation

  8. 2000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis

    International Nuclear Information System (INIS)

    Trentham, D.E.; Belli, J.A.; Bloomer, W.D.; Anderson, R.J.; Lane, H.; Reinherz, E.L.; Austen, K.F.

    1987-01-01

    Because toxicity with the use of 3000 centiGray (cGy) of total lymphoid irradiation (TLI) was observed in an earlier study, 2000-cGy treatments were delivered in a 2-portal format to 7 patients and in a modified 3-portal fashion to 6 patients, as part of a randomized, investigator-blinded trial of TLI treatment for refractory rheumatoid arthritis. Analysis of combined data from the 13 patients revealed statistically significant improvement in 5 clinical indicators of disease activity at the end of TLI and 6 and 12 months later, accompanied by T4-specific immunosuppression. Management considerations resulted in the introduction of prednisone therapy in 5 patients, methotrexate in 4, and azathioprine in 1 during the interval of 8-12 months post-TLI. Herpes zoster occurred in 5 patients prior to the initiation of this additional therapy. These data indicate that, in patients with rheumatoid arthritis, a TLI dose of 2000 cGy is sufficient to produce measurable benefit that lasts for 6 months, and that the improvement can be maintained at 12 months by the use of prednisone and methotrexate

  9. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

  10. Mizoribine: A New Approach in the Treatment of Renal Disease

    Directory of Open Access Journals (Sweden)

    Yukihiko Kawasaki

    2009-01-01

    Full Text Available Mizoribine (MZB is an imidazole nucleoside and an immunosuppressive agent. The immunosuppressive effect of MZB has been reported to be due to the inhibition of DNA synthesis in the S phase of the cell cycle. Because of its relative lack of toxicity, during the past decade MZB has been frequently used instead of azathioprine as a component of immunosuppressive drug regimens. MZB is being used to treat renal transplantation patients, IgA nephropathy, lupus erythematosus, and childhood nephrotic syndrome (NS, and some recent studies have assessed the efficacy of oral MZB pulse therapy for severe lupus nephritis, steroid-resistant NS, and frequently relapsing-steroid-dependent NS. This review summarizes the published findings on the efficacy of MZB for renal disease including IgA nephropathy, lupus nephritis, and NS, as well as of oral MZB pulse therapy for severe lupus nephritis and NS, and also the mechanism of the effect of oral MZB pulse therapy on the lymphocyte cell cycle.

  11. Benefits of early biopsy on the outcome of kidney transplantation.

    Science.gov (United States)

    Dominguez, J; Kompatzki, A; Norambuena, R; Arenas, J; Dell'Oro, A; Bustamante, A; Pinochet, R; Cabello, J M; Alvarez, S; Pais, E; Llanos, R; Cortes-Monroy, G

    2005-10-01

    Delayed graft function has been associated with worse long-term kidney allograft survival. Adequate diagnosis of the etiology of dysfunction is crucial, often requiring routine early biopsies. The aim of this article was to report the results and safety of early kidney allograft biopsies and how they influenced its management. Between September 1994 and July 2004, 134 renal transplant recipients were prescribed cyclosporine (CsA; Neoral, Novartis, Chile), steroids, and a third agent (azathioprine in 92% of the graft recipients). Thirty-four patients (26%) had a kidney biopsy performed within the first week because of allograft dysfunction. The main diagnosis was acute tubular necrosis (ATN) in 22 patients (65%), whereas 6 (18%) were diagnosed with an acute rejection episode (ARE), allowing prompt initiation of therapy with reversal of rejection in 4 of them. Two patients (6%) showed signs of thrombotic microangiopathy (TMA) induced by CsA, which subsided following a switch from CsA to tacrolimus (Prograf Pharmainvesti, Chile). In 2 patients, the biopsy specimen showed signs of CsA nephrotoxicity that reverted following dose reduction. Finally, in 2 patients, the biopsy specimen showed chronic nephropathy of donor origin, which had not been previously recognized, resulting in graft loss. There was only one major complication related to the biopsy, intraperitoneal bleeding that required surgical treatment. Early allograft biopsy is safe and, in a significant number of cases (30%), it detects important allograft pathology (ARE, TMA, and drug toxicity), which when adequately and promptly treated may rescue the graft.

  12. Alterations of the blood pool in the femoral head before and after renal transplantation

    International Nuclear Information System (INIS)

    Hamaguchi, Hiroyuki; Fujioka, Mikihiro; Inoue, Shigehiro; Shibatani, Masahiko; Kubo, Toshikazu; Kubota, Takao; Ushijima, Yo; Nishimura, Tsunehiko

    2003-01-01

    The pathogenesis of idiopathic osteonecrosis of the femoral head (ION) is thought to be an ischemic event. The purpose of this study is to investigate alterations of the blood pool in the femoral head before and after renal transplantation. After renal transplantation, all patients received the same immunosuppressive therapy: corticosteroids, cyclosporin-A, and azathioprine. We performed 3-phase bone scintigraphy on 16 renal allograft recipients within 1 week before renal transplantation, and between week 4 and 9 after renal transplantation. Regions of interest (ROI) were assigned bilaterally in the femoral head, diaphysis, and soft tissue. The head-to-diaphysis ratios (HD ratios) were then calculated. Idiopathic osteonecrosis of the femoral head occurred in 2 femoral heads of 1 patient. The HD ratio before renal transplantation (mean HD±SD, 1.52±0.30) and the HD ratio after renal transplantation (1.28±0.30) were significantly different (P=0.000024). The HD ratios before and after renal transplantation were significantly different, indicating that the administration of steroids diminished the blood pool in the femoral head. A low HD ratio before renal transplantation revealed a poor blood pool in the femoral head, which may be a risk factor for ION. (author)

  13. Mycophenolate mofetil for prevention of liver allograft rejection: initial results of a controlled clinical trial.

    Science.gov (United States)

    Sterneck, M; Fischer, L; Gahlemann, C; Gundlach, M; Rogiers, X; Broelsch, C

    2000-01-01

    Mycophenolate Mofetil (M MF) is a new immunosuppressive agent with proven efficacy for the prevention of kidney allograft rejection. However, only little experience is available with the use of MMF in liver transplant recipients. In this prospective, controlled trial the efficacy and safety of MMF and Azathioprine (AZA) were compared in a Neoral based quadruple immunosuppressive regimen after orthotopic liver transplantation. Between 12/96 and 12/98 57 adult patients were enrolled in the study at the University of Hamburg. 28 patients were randomised to MMF, 29 patients to AZA in combination with equivalent doses of lymphocyte antibodies, Neoral and methylprednisolone. After a median follow-up of 10+/-3.2 months patient or graft survival did not differ significantly between the MMF and AZA group. However, MMF treated patients experienced less frequently acute rejection episodes (MMF: 6/28; 21.4% versus AZA: 13/29; 44.8%) (p=0.06). Furthermore, thrombocytopenia (MMF: 6/28; 21.4% versus AZA: 14/29; 48.3%) (ppreliminary data suggest that after liver transplantation primary immunosuppression with MMF is advantageous over AZA with regard to safety and efficacy.

  14. A case of aortic and mitral valve involvement in granulomatosis with polyangiitis.

    Science.gov (United States)

    Espitia, Olivier; Droy, Laure; Pattier, Sabine; Naudin, Frédérique; Mugniot, Antoine; Cavailles, Arnaud; Hamidou, Mohamed; Bruneval, Patrick; Agard, Christian; Toquet, Claire

    2014-01-01

    Granulomatosis with polyangiitis (GPA) (Wegener's) is a necrotizing systemic vasculitis of the small-sized blood vessels, affecting kidneys, lungs, upper respiratory tract and skin. Cardiac valvular involvement is an uncommon manifestation of GPA. We report the case of a 60-year-old woman with arthritis and lung nodules due to GPA without antineutrophil cytoplasmic antibodies (ANCA) at time of diagnosis. Remission was obtained with cyclophosphamide and corticosteroid. Azathioprine was then prescribed for 2years. Four years later, she developed severe inflammatory aortic and mitral valvular involvement characterized by GPA typical histopathological valvular lesions. Search for ANCA was positive at this time (anti-myeloperoxidase). Cardiac valvular involvement is a rare and potentially fatal complication of GPA and may misleadingly suggest infectious endocarditis. A review of literature revealed few cases of histologically well-documented cardiac valvular involvement in GPA. Pathologists should be aware of valvular heart diseases in GPA, which usually comprise valvular necrotic lesions without any microbial agents. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Neuro-ophthalmologic manifestations of systemic lupus erythematosus: a systematic review.

    Science.gov (United States)

    Man, Bik Ling; Mok, Chi Chiu; Fu, Yat Pang

    2014-06-01

    Herein we summarize the clinical presentation, treatment and outcome of neuro-ophthalmologic manifestations in patients with systemic lupus erythematosus (SLE). We performed a systematic review of the neuro-ophthalmologic manifestations of SLE reported in the English literature from 1970 to 2010 by a Medline search. The prevalence of neuro-ophthalmologic manifestations is 3.6% in adult and 1.6% in childhood SLE patients. Neuro-ophthalmologic manifestations of SLE are highly variable, with the commonest presentation being optic neuritis, followed by myasthenia gravis, visual field defects and pseudotumor cerebri. The underlying pathology was thought to be either SLE activity or its vascular complications. Most neuro-ophthalmologic manifestations of SLE are responsive to high-dose glucocorticoids. Anticoagulation is indicated when there is concomitant antiphospholipid syndrome. SLE-related neuromyelitis optica is often refractory to treatment and 92% of patients require multiple immunosuppressive protocols. Neuro-ophthalmologic manifestations of SLE are uncommon but heterogeneous. The prognosis of neuro-ophthalmologic manifestations in SLE is generally good because of their rapid response to glucocorticoids. Relapses of these manifestations may be reduced by the use of maintenance immunosuppression. Cyclophosphamide, azathioprine, plasmapheresis, intravenous immunoglobulin and rituximab can be considered in glucocorticoid-dependent or refractory cases. Anticoagulation is indicated when there is concomitant antiphospholipid syndrome. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. [Dermatomyositis-update].

    Science.gov (United States)

    Volc-Platzer, B

    2015-08-01

    Dermatomyositis is a rare idiopathic inflammatory myopathy that affects adults and children, mostly female. Hallmarks of the disease are myositis with necrosis, regeneration and perifascicular atrophy accompanied by a typical skin rash with heliotrope erythema, Gottron's sign, Gottron's papules and nail fold changes with splinter hemorrhage. Typical skin symptoms may appear 6 months up to 2 years before muscle involvement (amyopathic dermatomyositis). New myositis-specific antibodies may allow clinicoserologic correlations within a heterogeneous clinical spectrum. Autoantibody profiles, subtype of myositis, overlap with other collagen vascular disorders and/or malignancy (paraneoplastic dermatomyositis) as well as age of the patients all have a considerable impact on course and prognosis. Infections, drugs and tumors may trigger activation of T and B cells, plasmacytoid dendritic cells, overproduction of type I interferons and complement-mediated endothelial cell damage resulting in vasculopathy. UV radiation may also trigger dermatomyositis. Oral corticosteroids (1.5-2.0 mg/kg body weight/day) are the mainstay of treatment until improvement of muscle symptoms and/or normalization of muscle enzymes with subsequent slow tapering. Corticosteroids may be given as monotherapy or combined with steroid-sparing immunosuppressive agents' i.e. azathioprine, methotrexate, mycophenolate mofetil or high-dose intravenous immunoglobulins. Prognosis has improved considerably since use of high-dose corticosteroids, from 50 to 90% response rate. New therapies with biologicals (anti-CD20-, anti-TNFalpha-, anti-interferon antibodies) and Janus kinase inhibitors are currently being evaluated.

  17. Disease course and therapeutic approach in dermatomyositis: A four-center retrospective study of 100 patients.

    Science.gov (United States)

    Johnson, Nicholas E; Arnold, W David; Hebert, Donald; Gwathmey, Kelly; Dimachkie, Mazen M; Barohn, Richard J; McVey, April L; Pasnoor, Mamatha; Amato, Anthony A; McDermott, Michael P; Kissel, John; Heatwole, Chad R

    2015-08-01

    Dermatomyositis is a life-altering inflammatory disorder of skin and muscle. Details regarding the natural course of this disorder, the effects of specific therapies on its progression, and the optimal therapeutic dosage and duration of prednisone are limited. We performed a retrospective medical record review of dermatomyositis patients at four medical centers. All patients were over the age of 21 and had a clinical diagnosis of dermatomyositis with pathological confirmation. We reviewed average muscle strength, corticosteroid use, creatine kinase levels, and supplemental immunosuppressant use during the 36-month period following each patient's initial assessment. One hundred patients participated with an average age of 50.1 years. Average muscle strength improved and prednisone requirements lessened six months after initial assessment. There was no difference in the mean change in muscle strength or cumulative corticosteroid use over 36 months among those initially treated with methotrexate, mycophenolate mofetil, pulse IVIG, or azathioprine. There was a 5% mortality rate in dermatomyositis patients due to infections. Treated dermatomyositis patients demonstrate the most significant improvement in strength during the first six-to-twelve months following their initial clinical assessment. Additional prospective studies are needed to determine the relative benefit of select immunosuppressant agents in preserving strength and reducing corticosteroid use in dermatomyositis. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Outcome of 235 renal transplant recipients followed up at ministry of health hospitals in the State of Johor.

    Science.gov (United States)

    Chan, A Y; Hooi, L S; Liu, W J

    2001-03-01

    Retrospective analysis was done on 235 recipients, 133 males and 102 females, who were transplanted between 25th September 1979 and 25th June 1999. 85.1% were Chinese, 7.7% were Indians and 7.2% Malays. 23% (54) were living related renal transplants (LRRT) all except 5 done at Hospital Kuala Lumpur. 60% (141) were living unrelated donor renal transplants (LURT) done in India. 17% (40) were cadaveric transplants (CADT) (all done in China except 2 at Hospital Kuala Lumpur and one in London). 97% (228) were first transplants. Primary renal disease was unknown in 69.4%, 17% (40) glomerulonephritis, 5.5% diabetic nephropathy and 8.1% 19 others. All were on prednisolone, 93.2% were on azathioprine and 96.6% were on cyclosporin A. The acute rejection rate was 23.4% (55 episodes). Patient survival was 88% at five years and patients alive with functioning graft was 84% at 5 years. LRRT had significantly better survival compared to LURT. 34 grafts were lost to chronic allograft nephropathy. 46 recipients died (33 died with functioning graft).

  19. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.

    LENUS (Irish Health Repository)

    Olaitan, Oyedolamu K

    2010-02-01

    To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.

  20. Common variable immunodeficiency associated with hepatosplenic T-cell lymphoma mimicking juvenile systemic lupus erythematosus.

    Science.gov (United States)

    Jesus, A A; Jacob, C M A; Silva, C A; Dorna, M; Pastorino, A C; Carneiro-Sampaio, M

    2011-01-01

    Common variable immunodeficiency (CVID) is a heterogeneous disorder with susceptibility to infections, autoimmune manifestations, and cancer. To our knowledge, CIVD with T-cell lymphoma mimicking juvenile systemic lupus erythematosus (JSLE) was not described in the literature, and one case was reported herein. An 8-year-old female was admitted in our Pediatric Immunology Unit with a clinical history of hypogammaglobulinemia, recurrent upper respiratory infections, and pneumonias. She had a marked decrease of three serum immunoglobulin isotypes, and the diagnosis of CVID was established. At the age of 17 years, she presented with oral ulceration, nonerosive arthritis, nephritis, serositis, cytopenia, positive antiphospholipid antibodies, and positive antinuclear antibody fulfilling the American College of Rheumatology (ACR) criteria for SLE. She was treated with intravenous methylprednisolone for three consecutive days, and intravenous immunoglobulin, and maintenance therapy of chloroquine, azathioprine and prednisone 40  mg/day. Two months later, she died of septic shock secondary to acute pneumonia. The necropsy showed hepatosplenic T-cell lymphoma with diffuse involvement of bone marrow, spleen, liver, and lungs. The lymphoma cells were positive for CD3 immunostaining and negative for CD20 and lysozyme. In conclusion, the association of CVID and hepatosplenic T-cell lymphoma may simulate JSLE diagnosis.

  1. A female soccer player with recurrent haemoptysis and iron deficiency anaemia: idiopathic pulmonary haemosiderosis (IPH)-case report and literature review.

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    Schroers, Roland; Bonella, Francesco; Tötsch, Martin; Costabel, Ulrich

    2010-01-01

    A 19-year-old woman presented with repeated episodes of haemoptysis and shortness of breath. Blood tests revealed iron deficiency anaemia and chest imaging studies showed bilateral lung opacities. In further laboratory tests and technical examination including bronchoalveolar lavage and transbronchial lung biopsy, pulmonary embolism, cardiac disease, and pulmonary vasculitis due to autoimmune disease were ruled out. Finally, a diagnosis of idiopathic pulmonary haemosiderosis (IPH) was made in January 2008. The patient was treated with prednisone, azathioprine, and oral iron supplementation. Subsequently, the patient's condition and haemoglobin value improved notably. In May 2009, the patient was in full disease remission including a normal blood count and normal iron parameters. IPH is a rare cause of diffuse alveolar haemorrhage of unknown origin. It occurs most frequently in children and adolescents and typically presents with recurrent haemoptysis due to alveolar bleeding. However, pulmonary signs and symptoms often are obscure in children. In these cases iron deficiency anaemia is the prominent clinical finding. The purpose of this case report is to increase awareness of IPH as a possible cause of recurrent haemoptysis and anaemia.

  2. Nodular Epiescleritis Granulomatous Canine. Case Report

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    Camilo Guarín Patarroyo

    2011-12-01

    Full Text Available Granulomatous epiescleritis nodular disease in canines is a very unusual presentation that affects or external fibrous tunic of the eyeball and conjunctiva, which was an increase similar to a unilateral or bilateral tumor. Suspected immune-mediated disease due to lack of identification of an etiologic agent and the response to treatment with immunosuppressive drugs (Couto, 1992. The ideal therapy is the application of steroids via intralesional, topical or systemic, or other immunosuppressants such as cyclosporine and azathioprine; it is still advisable to apply antibiotic is the ideal combination of tetracycline and neomycin (Gilger & Whitley, 1999. The diagnostic method of episcleritis is made by histopathology, which is evident in changes similar to chronic granulomatous inflammation. Are claiming a racial bias in Alsatian, Shepherd Collie Shetland Shepherd, Coker Spaniel, Rottweiler and Labrador Retriever (Gough & Thomas, 2004. The following case is a report of a nodular epiescleritis affecting the cornea, sclera, and the corneoscleral limbus, which describes the diagnosis, signology and treatment.

  3. Cardiovascular Comorbidity in Inflammatory Rheumatological Conditions.

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    Braun, Jürgen; Krüger, Klaus; Manger, Bernhard; Schneider, Matthias; Specker, Christof; Trappe, Hans Joachim

    2017-03-24

    Approximately 1.5 million adults in Germany suffer from an inflammatory rheumatological condition. The most common among these are rheumatoid arthritis and spondyloarthritis-above all axial spondyloarthritis, including ankylosing spondylitis (Bekhterev's disease) and psoriatic arthritis. These systemic inflammatory diseases often affect the heart as well. This review is based on pertinent articles retrieved by a selective literature search, on current European guidelines, and on the authors' clinical experience. Rheumatic inflammation of cardiac structures can manifest itself as pericarditis, myocarditis, or endocarditis. The heart valves and the intracardiac conduction system can be affected as well, leading to AV block. Functional sequelae, e.g., congestive heart failure, can arise as a consequence of any inflammatory rheumatic disease. The long-term mortality of rheumatic diseases is elevated predominantly because of the increased risk for cardiovascular comorbidities. The cardiovascular risk profile should therefore be re-evaluated regularly (e.g., at 5-year intervals) in cooperation with the patient's primary care physician. The cardiovascular manifestations of rheumatic disease, such as pericarditis, myocarditis, and vasculitis, are treated initially with high-dose glucocorticoids and then over the long term with maintenance drugs such as methotrexate and azathioprine. Biological agents are sometimes used as well. In patients with inflammatory rheumatic diseases, the elevated cardiovascular risk should be kept in mind and preventive measures should be initiated early. This subject should be further studied in controlled trials so that the treatment options for patients with cardiac involvement can be evaluated.

  4. Discussion: DMARDs and biologic therapies in the management of inflammatory joint diseases.

    Science.gov (United States)

    Vaz, Austin; Lisse, Jeffrey; Rizzo, Warren; Albani, Salvatore

    2009-05-01

    Therapy for inflammatory joint diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, includes various conventional disease-modifying antirheumatic drugs (DMARDs). These therapeutic agents are termed DMARDs because they have the potential to reduce or prevent joint damage and preserve joint integrity and function. Conventional DMARDs are used as monotherapy or in combination and include methotrexate, leflunomide, azathioprine, ciclosporin, hydroxychloroquine, sulfasalazine, gold and minocycline. Biologic response modifiers, which are based on proteins made by living cells, are newer agents available for the treatment of various inflammatory joint diseases. Biologic therapies now approved for use in inflammatory joint diseases are TNF inhibitors, T-cell modulators and B-cell depleters. They have all been shown to have clinical efficacy and are able to retard structural damage. However, all current immune-modulating therapies also have potential side effects, and the decision to use a particular agent for treatment should be based on a thorough discussion of the benefits and risks with the patient. Newer biologic response modifiers and other immunologic therapies are currently being developed for the treatment of inflammatory joint diseases and are discussed in this review.

  5. Renal manifestations in hypocomplementic urticarial vasculitis syndrome: Is it a distinct pathology?

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    Badriya AlHermi

    2017-01-01

    Full Text Available Hypocomplementic urticarial vasculitis syndrome (HUVS is an autoimmune disease characterized by recurrent urticaria, arthritis, and glomerulonephritis (GN. Anti-C1q antibody is the marker of HUVS together with low levels of classical pathway complements which are C2, C3, C4, and C1q. We report a case of a 6-year-old boy who presented with episodes of rashes, injected conjunctiva, abdominal pain, and arthritis, diagnosed as HUVS. He had low C3, low CH50, normal C4, and positive C1q antibody. His urinalysis showed intermittent microscopic hematuria only. One year later, his laboratories showed persistent low C3 and positive Anti-ds DNA. The urinalysis showed hematuria, pyuria, and nephrotic-range proteinuria. Urine protein to creatinine ratio was 101.8 h mg/mmol. Kidney biopsy showed mesangioproliferative GN consistent with the diagnosis of HUVS. The patient was treated initially with prednisolone then azathioprine was added to the regimen. He showed good response with the disappearance of hematuria and proteinuria. Nine months later, he had no skin rashes with normal urinalysis and normal anti-ds DNA antibody. We report a case with HUVS and GN with positive anti-dsDNA antibody that revealed good response to combination of immunosuppressive therapy.

  6. A case of exorbitism in association with Wegener′s granulomatosis with renal involvement

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    S Beji

    2012-01-01

    Full Text Available Wegener′s granulomatosis (WG is a necrotizing granulomatous vasculitis invol-ving the nose, paranasal sinuses, lungs, and kidneys. Ocular involvement can occur in about 50% of cases. There are very few reports of WG with orbital inflammation and exorbitism. We report a case of a female patient who presented with exorbitism related to orbital inflammation secondary to WG, with renal involvement. A 29-year-old woman with a previous history of recurrent pan-sinusitis presented with bilateral exophthalmos and renal failure with rapidly progressive glo-merulonephritis. Computed tomography showed extensive bilateral soft tissue in the retro-orbital area. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies and renal biopsy revealed pauci immune crescentic glomerulonephritis. The patient was treated with corticosteroids and pulses of cyclophosphamide followed by azathioprine and trimethoprim-sulfamethoxazole. After a follow-up of 10 months, the renal outcome was favorable with improvement of renal function but there was persistence of exorbitism and loss of visual function. Our case suggests that WG should be considered in the differential diagnosis of persistent bila-teral exophthalmos. Prompt recognition of this early manifestation is important for the institution of early treatment.

  7. Strategies for Preventing Endoscopic Recurrence of Crohn’s Disease 1 Year after Surgery: A Network Meta-Analysis

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    Jin-shan Feng

    2017-01-01

    Full Text Available Objective. To assess the benefits of different treatments that aim to prevent the endoscopic recurrence of Crohn’s disease (CD after ileal resection. Methods. Randomized controlled trials (RCTs were searched from MEDLINE, Embase, and the Cochrane Central Database. All the included RCTs with an endoscopic recurrence outcome which was defined as Rutgeerts’ score ≥ i2 have a duration of more than 1 year. The quality of the included RCTs was assessed by the Cochrane Risk of Bias Tool. Pairwise treatment effects were estimated through a Bayesian random effects network meta-analysis by using the OpenBUGS 1.4 software and reported as odds ratios (ORs with a 95% credible interval (CI. Results. Fourteen RCTs (877 participants were included. Two strategies were superior to placebo for preventing endoscopic recurrence of CD at 1 year after surgery: infliximab (d, −5.475; 95% CI, −10.47 to –1.632 and adalimumab (d, −7.273; 95% CI, −13.84 to −2.585. Nine strategies were not effective: budesnoid, mesalazine (in both high and low dose, azathioprine, Tripterygium wilfordii, mesalazine + infliximab, ornidazole, untreated intervention, and Lactobacillus GG. Conclusions. Except for infliximab and adalimumab, other strategies included in our analysis were not effective for preventing endoscopic recurrence of CD at 1 year after ileal resection.

  8. Vulvovaginal gingival lichen planus: report of two cases and review of literature.

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    Lucchese, A; Dolci, A; Minervini, G; Salerno, C; DI Stasio, D; Minervini, G; Laino, L; Silvestre, F; Serpico, R

    2016-01-01

    Oral Lichen Planus (OLP) is a chronic inflammatory disease of skin and mucous membranes. Approximately 20% of women with oral lichen planus develops lesions in the genital mucosa. In 1982, Pelisse described a special form of lichen planus (LP), which consists of a triad of symptoms: vulval, vaginal and gingival (VVG)-LP lesions. Aim of the present report is to report two new cases and review the international literature. Two cases of VVG-LP are reported and a review of recent literature is performed. The onset of erosive or ulcerative mouth lesions may precede or follow by months or even years the onset of vulvovaginal lesions. Vaginal agglutination is associated with the postmenopausal state in conjunction with a dermatologic condition. Intra-lesional corticosteroids have a role in localized chronic ulceration, while systemic therapies such as corticosteroids, azathioprine, mycophenolate mofetil, hydroxychloroquine, ciclosporin, methotrexate, retinoids, thalidomide and photo chemotherapy have been used in more severe cases with varying success. VVG-LP is rather a rare condition and has been documented in the literature mainly in the form of case reports. Lack of a precise diagnostic criteria of VVG-LP depends on the specialists.

  9. Myasthenia gravis in children: analysis of 18 patients

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    Morita Maria da Penha A.

    2001-01-01

    Full Text Available Myasthenia gravis (MG in childhood is rare comprising 10 to 20 % of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1. Eleven patients (61% presented moderate or severe generalized disease and 4 (22% had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47% out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6% (9 out of 11 tested and the levels had no relation to clinical severity. Nine out of 16 patients (56% worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia. Three patients (75% improved markedly after thymectomy and one (25% worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child.

  10. [Clinical Features and Treatment of Hashimoto Encephalopathy].

    Science.gov (United States)

    Maki, Yoshimitsu; Takashima, Hiroshi

    2016-09-01

    Hashimoto encephalopathy (HE) is characterized by heterogeneous neurological symptoms. HE is diagnosed based on three criteria-the presence of antithyroid antibodies, neurological symptoms from the cerebrum and/or cerebellum, and a positive response to immunotherapy. We clinically analyzed 18 patients (3 men, 15 women; age range, 38-81years) diagnosed with HE in our hospital from May 2013 to January 2016. Eleven patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or neuralgia. Surprisingly, the majority of the pain was distributed in a manner that was not explainable anatomically. Seventeen patients showed motor disturbances, such as weakness, paresis of extremities, or dexterity movement disorder, and eight patients showed give-way weakness, which is disruption of continuous muscle contraction. Other symptoms indicative of brain-related anomalies such as tremor, dystonia, involuntary movements, cerebellar ataxia, parkinsonism, memory loss, and chronic fatigue were also seen. In most patients, such motor, sensory, or higher brain functions were markedly improved with immunosuppressive therapies such as prednisolone, azathioprine, or immunoadsorption therapy. Although give-way weakness and anatomically unexplainable pain are typically considered as being psychogenic in origin, the presence of these symptoms is indicative of HE. HE exhibits diffuse involvement of the entire brain and thus, these symptoms are explainable. We propose that physicians should not diagnose somatoform disorders without first excluding autoimmune encephalopathy.

  11. The first childhood case with coexisting Hashimoto thyroiditis, vitiligo and autoimmune hepatitis.

    Science.gov (United States)

    Keskin, Melikşah; Savaş-Erdeve, Şenay; Özbay-Hoşnut, Ferda; Kurnaz, Erdal; Çetinkaya, Semra; Aycan, Zehra

    2016-01-01

    Hashimoto thyroiditis (HT) is the most common pediatric autoimmune endocrine disorder. It results in autoimmune-mediated thyroid gland destruction and is an organ-specific, typical autoimmune disease. The presence of antithyroid antibodies and the typical pattern on ultrasonography indicate the diagnosis. It is also frequently seen together with other autoimmune disorders including type 1 insulin-dependent diabetes, celiac disease, alopecia and vitiligo. Autoimmune hepatitis (AIH) is a chronic type of liver injury with an immune etiology that can frequently cause end-stage liver disease if left untreated. Autoimmune hepatitis patients may present with hepatitis, and the laboratory tests in the absence of other etiology usually reveal a positive immune serology together with elevated immunoglobulins and abnormal liver histology. It is interesting that HT and AIH are rarely seen together although both have an autoimmune etiology. 14-year-old male who was being followed-up for vitiligo presented with symptoms of a swelling at the neck and fatigue. He was diagnosed with HT after the tests and the liver enzymes were found to be high. The patient was also diagnosed with AIH after tests revealed that the liver enzyme elevation had continued for longer than six months. The thyroid functions and liver enzymes returned to normal and the symptoms decreased after sodium L-thyroxine replacement together with steroid and azathioprine treatment. We present this case as we believe it is the first pediatric patient diagnosed with HT, AIH and vitiligo.

  12. Juvenile systemic lupus erythematosus in Nigeria.

    Science.gov (United States)

    Adelowo, O O; Olaosebikan, B H; Animashaun, B A; Akintayo, R O

    2017-03-01

    Juvenile systemic lupus erythematosus (JSLE) is a complex multisystemic autoimmune disorder of unknown cause. It accounts for about one in five cases of SLE. The tendency for SLE to run a fulminant course when it starts in childhood has made JSLE a potentially more severe disease than adult SLE. Reports of JSLE from sub-Saharan Africa are scanty in spite of the increasing reports of adult SLE. We conducted a 4-year retrospective study of JSLE cases seen at the Lagos State University Teaching Hospital between January 2010 and December 2014. Out of the 12 patients studied, eight were girls and four were boys. All patients had positive antinuclear antibody and extractable nuclear antibody tests. Anti-dsDNA antibody was positive in 10 patients. Eight patients had renal disease while four patients had neuropsychiatric manifestations. Haematological abnormalities and constitutional symptoms were present in all patients. Patients were treated with pulse methylprednisolone, oral prednisolone, hydroxychloroquine and azathioprine. Three patients also received rituximab. In conclusion, JSLE exists in Nigeria and exhibits clinical and immunological characteristics similar to its pattern in other parts of the world. It is, however, diagnosed late and is possibly being underdiagnosed as there is no paediatric rheumatologist in the country.

  13. Lymphoma risk in systemic lupus: effects of disease activity versus treatment

    Science.gov (United States)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence; Boivin, Jean-Francois; Costenbader, Karen H; Urowitz, Murray B; Gladman, Dafna D; Fortin, Paul R; Nived, Ola; Petri, Michelle A; Jacobsen, Soren; Manzi, Susan; Ginzler, Ellen M; Isenberg, David; Rahman, Anisur; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Yelin, Edward; Bae, Sang-Cheol; Wallace, Daniel J; Peschken, Christine A; Dooley, Mary Anne; Edworthy, Steven M; Aranow, Cynthia; Kamen, Diane L; Romero-Diaz, Juanita; Askanase, Anca; Witte, Torsten; Barr, Susan G; Criswell, Lindsey A; Sturfelt, Gunnar K; Blanco, Irene; Feldman, Candace H; Dreyer, Lene; Patel, Neha M; Pierre, Yvan St; Clarke, Ann E

    2013-01-01

    Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case–cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren’s syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE. PMID:23303389

  14. Thiopurines inhibit bovine viral diarrhea virus production in a thiopurine methyltransferase-dependent manner.

    Science.gov (United States)

    Hoover, Spencer; Striker, Rob

    2008-04-01

    The family Flaviviridae comprises positive-strand RNA viral pathogens of humans and livestock with few treatment options. We have previously shown that azathioprine (AZA) has in vitro activity against bovine viral diarrhea virus (BVDV). While the mechanism of inhibition is unknown, AZA and related thiopurine nucleoside analogues have been used as immunosuppressants for decades and both AZA metabolites and cellular genes involved in AZA metabolism have been extensively characterized. Here, we show that only certain riboside metabolites have antiviral activity and identify the most potent known antiviral AZA metabolite as 6-methylmercaptopurine riboside (6MMPr). The antiviral activity of 6MMPr is antagonized by adenosine, and is specific to BVDV and not to the related yellow fever virus. An essential step in the conversion of AZA to 6MMPr is the addition of a methyl group onto the sulfur atom attached to position six of the purine ring. Intracellularly, the methyl group is added by thiopurine methyltransferase (TPMT), an S-adenosyl methionine-dependent methyltransferase. Either chemically bypassing or inhibiting TPMT modulates antiviral activity of AZA metabolites. TPMT exists in several variants with varying levels of activity and since 6MMPr is a potent antiviral, the antiviral activity of AZA may be modulated by host genetics.

  15. Unusual Case of Cerebral Venous Thrombosis in Patient with Crohn's Disease

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    Inha Kim

    2015-05-01

    Full Text Available The development of cerebral venous thrombosis (CVT as a secondary complication of Crohn's disease (CD seems to be rare, but it is generally accepted that the disease activity of CD contributes to the establishment of a hypercoagulable state. Here, we describe a case of CVT that developed outside the active phase of CD. A 17-year-old male visited the emergency room because of a sudden onset of right-sided weakness and right-sided hypesthesia. He had been diagnosed with CD 1 year before and was on a maintenance regimen of mesalazine and azathioprine. He did not exhibit any symptoms indicating a CD flare-up (bloody stools, abdominal pain, complications, or weight loss. A brain MRI scan revealed an acute infarction of the left frontal cortex and a cortical subarachnoid hemorrhage. Additionally, a magnetic resonance venography revealed a segmental filling defect in the superior sagittal sinus and also the non-visualizability of some bilateral cortical veins. The characteristics of the present case suggest that the risk of CVT is most likely related to CD per se rather than disease activity associated with CD.

  16. Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

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    A. Oglesby

    2013-01-01

    Full Text Available This paper assessed the burden of adverse events (AEs associated with azathioprine (AZA, cyclophosphamide (CYC, mycophenolate mofetil (MMF, methotrexate (MTX, and cyclosporine (CsA in patients with systemic lupus erythematosus (SLE. Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%, gastrointestinal AEs (3.2–66.7%, and amenorrhea and/or ovarian complications (0–71%. More hematological cytopenias were associated with AZA (14 episodes than MMF (2 episodes. CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp. or AZA (17–77% versus 11–29%, resp.. Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp. or AZA (32–71% versus 8–18%, resp.. Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

  17. Impact of positive PRA on the results of ABO-incompatible kidney transplantation.

    Science.gov (United States)

    Shimmura, H; Tanabe, K; Tokumoto, T; Ishida, H; Ishikawa, N; Miyamoto, N; Shimizu, T; Shirakawa, H; Setoguchi, K; Toma, H

    2004-09-01

    Due to the continuing shortage of cadaveric donors in Japan, ABO-incompatible living kidney transplantation (LKT) is being performed. It is well known that highly sensitized patients with positive panel reactive antibodies (PRA) often present with acute rejection. Therefore, we examined the impact of a positive PRA on the results of ABO-incompatible LKT. One hundred seventy-seven recipients underwent ABO-incompatible LKT between January 1989 and March 2003. Of these patients, 37 who had been examined for PRA before transplantation were included in this study. There were 25 men and 12 women of mean age 37.3 years. Plasmapheresis was performed to remove anti-ABO antibodies before transplantation. During the induction phase, methylprednisolone, azathioprine, or mycophenolate mofetil and cyclosporine or tacrolimus were used for immunosuppression. Splenectomy was performed at the time of kidney transplantation in all patients. PRA was measured using FlowPRA by flow cytometer. Eight of the 37 patients had a positive PRA before transplantation (class I, 5; class II, 1; class I and class II, 2). The incidence of acute rejection was 37.9% in the patients with a negative PRA and 37.5% in patients with a positive PRA. One patient with a negative PRA and one patient with a positive PRA lost grafts due to acute rejection. Positive PRA may not increase the incidence of acute rejection in ABO-incompatible LKT because plasmapheresis and splenectomy are performed to eliminate anti-ABO antibody.

  18. Late acute antibody mediated rejection after nine years of renal transplantation

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    Halim Medhat

    2010-01-01

    Full Text Available Acute Antibody Mediated Rejection (AMR is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA and cyclosporine A (CsA. Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr. to 210 μmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN with focal crescent formation, diffuse immune complex deposition and peri-tubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab. AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 μmol/L.

  19. Pênfigo foliáceo canino: estudo retrospectivo de 43 casos clínicos e terapia (2000-2005 Canine Pemphigus foliaceus: a retrospective study of 43 clinical cases and therapy (2000-2005

    Directory of Open Access Journals (Sweden)

    Ana C. Balda

    2008-08-01

    Full Text Available No período de agosto de 2000 a julho de 2005 foram atendidos 43 casos de Pênfigo Foliáceo (PF canino no Serviço de Dermatologia do Hospital Veterinária, Universidade de São Paulo. Com este estudo retrospectivo visou-se atualizar dados referentes à caracterização sexual, definição racial e raça, idade, tipo e topografia lesional, quadro sintomático e resposta aos tratamentos isolados com prednisona e com a associação desta à azatioprina, além de demonstrar o aumento na ocorrência do PF relativamente à série histórica pretérita (1986-2000 do mesmo Serviço.From August 2000 to July 2005 were attended 43 cases of canine Pemphigus foliaceous (PF by the Dermatology Service of the Veterinary Teaching Hospital, University of São Paulo. The aim of the present study was to update the records referred to sex, breed, age, type and location of the lesions, clinical signs, and response to treatments with prednisone or combination with prednisone and azathioprine, and also to demonstrate the increase of occurrence of PF compared with the former series (1986-2000 observed in the same Service.

  20. [Osteo-articular complications of heart transplantation].

    Science.gov (United States)

    Rozenberg, S; Bourgeois, P

    1995-12-09

    Heart transplantation is an effective means of treating irreversible heart failure in selected patients. Preventing organ rejection requires immunosuppressor treatment with corticosteroids, azathioprine and/or cyclosporine. Bone and joint complications are frequent and increase overall morbidity directly related to anti-rejection therapy. Corticosteroids favour osteopenia which can be detected by measurement of bone density. The risks include spontaneous wedge fractures of the spine and aseptic necrosis. The frequency of complications has been reduced with the use of cyclosporine allowing a reduction in corticosteroids. Raised serum urate levels and increased risk of gout can be induced by cyclosporine. The gout in these patients has a particular course since it appears rapidly after only a few months of hyperuricaemia. Several joints may be involved with production of tophi. Treatment is particularly difficult. Its frequency increases after heart transplantation compared with other organs which can be explained by the more prevalent prescription of diuretics which further aggravate urate secretion. These complications cause further discomfort in transplant recipients.

  1. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    International Nuclear Information System (INIS)

    Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

    1984-01-01

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced

  2. Intramyocardial electrogram recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.

    Science.gov (United States)

    Knosalla, C; Grauhan, O; Muller, J; Pfitzmann, R; Fietze, E; Cohnert, T; Volk, H D; Hetzer, R

    2000-04-01

    The purpose of this study was to prove the reliability of intramyocardial electrogram (IMEG) recordings for diagnosis and treatment monitoring of (1) cellular and (2) humoral mediated allograft rejection after heart transplantation. Fifteen beagle dogs underwent heterotopic neck-heart transplantation. Eight of them were previously sensitized through several skin transplantations. IMEG recordings were performed daily. Donor-specific antibodies (IgG, IgM) were determinated in serum daily. Transmyocardial biopsies were performed every two days. In the sensitized group (group I) accelerated rejection occurred under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone on the fifth postoperative day (range: 4th-5th). All episodes were detected through IMEG diagnosis. In each case rejection could be treated successfully. In the cellular mediated group (group II), the average sensitivity for rejection diagnosis of a single lead was 24% for the unipolar and 42% for the bipolar leads. When the voltages of different leads were summed up the sensitivity rose to 36% (3 unipolar), 81% (3 bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 hours. The IMEG detects cellular and humoral mediated rejection early and with high reliability. The rejection-related changes of grade 2/3a rejection in IMEG seem to follow a Ofocal patternO similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance diagnostic reliability.

  3. Vulvovaginal gingival lichen planus: report of two cases and review of literature

    Science.gov (United States)

    LUCCHESE, A.; DOLCI, A.; MINERVINI, G.; SALERNO, C.; DI STASIO, D.; MINERVINI, G.; LAINO, L.; SILVESTRE, F.; SERPICO, R.

    2016-01-01

    SUMMARY Purpose Oral Lichen Planus (OLP) is a chronic inflammatory disease of skin and mucous membranes. Approximately 20% of women with oral lichen planus develops lesions in the genital mucosa. In 1982, Pelisse described a special form of lichen planus (LP), which consists of a triad of symptoms: vulval, vaginal and gingival (VVG)-LP lesions. Aim of the present report is to report two new cases and review the international literature. Material and methods Two cases of VVG-LP are reported and a review of recent literature is performed. Results The onset of erosive or ulcerative mouth lesions may precede or follow by months or even years the onset of vulvovaginal lesions. Vaginal agglutination is associated with the postmenopausal state in conjunction with a dermatologic condition. Intra-lesional corticosteroids have a role in localized chronic ulceration, while systemic therapies such as corticosteroids, azathioprine, mycophenolate mofetil, hydroxychloroquine, ciclosporin, methotrexate, retinoids, thalidomide and photo chemotherapy have been used in more severe cases with varying success. Conclusions VVG-LP is rather a rare condition and has been documented in the literature mainly in the form of case reports. Lack of a precise diagnostic criteria of VVG-LP depends on the specialists. PMID:28042431

  4. Factors influencing the progression of fibrosis in patients with recurrent hepatitis C after liver transplantation under antiviral therapy: a retrospective analysis of 939 liver biopsies in a single center.

    Science.gov (United States)

    Walter, Thomas; Dumortier, Jérôme; Guillaud, Olivier; Hervieu, Valérie; Scoazec, Jean-Yves; Boillot, Olivier

    2007-02-01

    Recurrent hepatitis C after liver transplantation (LT) is a major problem, since up to 30% of patients develop cirrhosis only 5 years after LT in the absence of antiviral therapy. The aim of this study was to examine the rate of progression of fibrosis and its associated risk factors in patients submitted to an early antiviral treatment post-LT. Included in the study were 105 patients submitted to LT between September 1990 and December 2004, 70 of whom were treated with interferon and/or ribavirin. A total of 939 liver biopsies were studied. The median fibrosis stage was 0.8 after 1 year post-LT, 1.1 after 3 years, 1.3 after 5 years, and 1.5 after 10 years. LT recipients with fibrosis >2 (13% at 10 years) had a significantly reduced survival rate (63% vs. 87% at 10 years, P = 0.03). Univariate analysis disclosed that recipient male gender, antiviral therapy before LT, LT after 1998, induction immunosuppressive regimen including tacrolimus, induction immunosuppressive regimen including mycophenolate (or without azathioprine), and short duration of prednisolone (time and that occurrence of severe fibrosis is related to previously described factors related to immunosuppressive regimen or donor age and also to a past history of pre-LT antiviral therapy. (c) 2007 AASLD.

  5. Optimal Method to Stimulate Cytokine Production and Its Use in Immunotoxicity Assessment

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    Huiming Chen

    2013-08-01

    Full Text Available Activation of lymphocytes can effectively produce a large amount of cytokines. The types of cytokines produced may depend on stimulating reagents and treatments. To find an optimal method to stimulate cytokine production and evaluate its effect on immunotoxicity assessments, the authors analyzed production of IL-2, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, GM-CSF, RANTES and TGF-β in undiluted rat whole blood culture (incubation for 0, 2, 4, 6, 8 or 10 h with different concentrations of PMA/ionomycin, PHA, Con A, LPS and PWM. We also evaluated the effects of cyclosporin A and azathioprine on cytokine production. The results revealed a rapid increase of IL-2, IFN-γ, TNF-α, RANTES and TGF-β secretion within 6 h after stimulation with 25 ng/mL PMA and 1 μg/mL ionomycin. The inhibition of these cytokine profiles reflected the effects of immunosuppressants on the immune system. Therefore, the results of this is study recommend the detection of cytokine profiles in undiluted whole blood stimulated 6 h with 25 ng/mL PMA and 1 μg/mL ionomycin as a powerful immunotoxicity assessment method.

  6. Current and emerging treatment options in the management of lupus

    Science.gov (United States)

    Jordan, Natasha; D’Cruz, David

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

  7. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-01-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis

  8. Clinical Trial of FK 506 Immunosuppression in Adult Cardiac Transplantation

    Science.gov (United States)

    Armitage, John M.; Kormos, Robert L.; Morita, Shigeki; Fung, John; Marrone, Gary C.; Hardesty, Robert L.; Griffith, Bartley P.; Starzl, Thomas E.

    2010-01-01

    The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient. PMID:1379032

  9. Myasthenia gravis: subgroup classification and therapeutic strategies.

    Science.gov (United States)

    Gilhus, Nils Erik; Verschuuren, Jan J

    2015-10-01

    Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Recurrent pericarditis: new and emerging therapeutic options.

    Science.gov (United States)

    Imazio, Massimo; Lazaros, George; Brucato, Antonio; Gaita, Fiorenzo

    2016-02-01

    Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20-50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition.

  11. Immunosuppression and temporary skin transplantation in the treatment of massive third degree burns.

    Science.gov (United States)

    Burke, J F; Quinby, W C; Bondoc, C C; Cosimi, A B; Russell, P S; Szyfelbein, S K

    1975-01-01

    A method of burn treatment (immunosuppression and temporary skin transplantation) for patients suffering from massive third degree burns is evaluated. The method is based on the prompt excision of all dead tissue (burn eschar) and immediate closure of the wound by skin grafts. Total wound closure is achieved before bacterial infection or organ failure takes place by carrying out all initial excision and grafting procedures within the first ten days post burn and supplementing the limited amount of autograft with allograft. Continuous wound closure is maintained for up to 50 days through immunosuppression. Both azathioprine and ATG have been used but ATG is preferred. During the period of immunosuppression, allograft is stepwise excised and replaced with autograft donor sites regenerate for recropping. Bacterial complications are minimized by housing the patient in the protected environment of the Bacteria Controlled Nursing Unit. Intensive protein and calorie alimentation are provided, and 0.5% aqueous AgNO3 dressings are used. A swinging febrile illness has been associated with large areas of allograft rejection. Eleven children have been treated and seven have been returned to normal, productive schooling. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:809014

  12. Immunotherapy of Crohn's disease

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    C. van Montfrans

    1998-01-01

    Full Text Available Although the initiating events of Crohn's disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn's disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti-inflammatory agents (corticosteroids, aminosalicylates to the use of immunomodulatory drugs (azathioprine, methotrexate. Moreover, novel strategies have been designed for specific targets in Crohn's disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid-refractory Crohn's disease with anti- CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti-tumour necrosis factor (TNF-α antibodies induced com plete remissions and few side effects were observed. One study suggested efficacy in active Crohn's disease of recombinant interleukin-10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn's disease, where disease-modifying interventions and strategies that effectively maintain disease remission will play a key role.

  13. Aprepitant for the Treatment of Chronic Refractory Pruritus

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    Alice He

    2017-01-01

    Full Text Available Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV. Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin’s lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks. Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant’s role is difficult to understand based on the current literature. Herein, we evaluate aprepitant’s antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy.

  14. Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis

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    İlknur Tuğal-Tutkun

    2016-04-01

    Full Text Available Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

  15. Long-term follow-up and treatment of congenital alveolar proteinosis

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    Muensterer Oliver J

    2011-08-01

    Full Text Available Abstract Background Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP due to mutations in the GM-CSF receptor are not well known. Case presentation A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child. Conclusions The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.

  16. Cardiac involvement in primary systemic vasculitis and potential drug therapies to reduce cardiovascular risk.

    Science.gov (United States)

    Misra, Durga Prasanna; Shenoy, Sajjan N

    2017-01-01

    Cardiac involvement is common in primary systemic vasculitides and may be due to direct effect of the disease on the heart or due to therapy. We shall review involvement of the heart in the various forms of primary systemic vasculitis. Among anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), eosinophilic granulomatosis with polyangiitis most commonly involves the heart. Involvement of the heart confers poorer prognosis in AAV, which is also complicated by increased risk of cardiovascular events. Kawasaki's disease (KD) is the most common form of medium-vessel vasculitis to affect the heart, with coronary artery aneurysms being the most common manifestation. These predispose patients with KD to develop premature ischemic heart disease. Takayasu's arteritis is the most common large-vessel vasculitis to involve the heart and can result in aortic incompetence, myocarditis, or coronary heart disease. Involvement of the heart in Behcet's disease is usually in the form of intracardiac mass lesions, thrombosis, or endomyocardial fibrosis. Drugs used in the treatment of systemic vasculitis influence the risk of developing cardiovascular events. Corticosteroid therapy has been shown to increase the risk of myocardial infarction, whereas methotrexate, azathioprine, mycophenolate mofetil, rituximab, and anti-tumor necrosis alpha agents favorably modulate the risk of cardiovascular events, predominantly by dampening systemic inflammation. Awareness of cardiac involvement in vasculitis and accelerated cardiovascular risk in these patients should help clinicians to maximize the modulation of modifiable risk factors for heart disease in these individuals.

  17. Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study.

    Science.gov (United States)

    Hu, Stephen Chu-Sung; Yen, Feng-Lin; Wang, Tsu-Nai; Lin, Yu-Chih; Lin, Chi-Ling; Chen, Gwo-Shing

    2016-07-01

    The association between immunosuppressive medication use and herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE) has not been clearly defined. We evaluated the risk of HZ in patients with SLE treated with different immunosuppressants. A nationwide population-based case-control study was conducted using the Taiwanese National Health Insurance Research Database. Cases (1555 patients with SLE who developed HZ) and controls (3049 age- and sex-matched patients with SLE but without HZ) were analyzed for use of various immunosuppressive medications in the preceding 3-month period, and dose-response relationships were determined. Logistic regression was performed to estimate the adjusted odds ratio for HZ development. Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose. This study is retrospective in nature. Recent immunosuppressive medication use is associated with increased HZ risk in patients with SLE, particularly those receiving high-dose oral corticosteroids and multiagent immunosuppressive therapy. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Successful Discontinuation of Infliximab in a Refractory Case of Vasculo-Behçet Disease

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    Akihiro Nakamura

    2016-01-01

    Full Text Available Reports have shown that antitumor necrosis factor alpha (anti-TNF-α agents including infliximab (IFX can dramatically suppress the disease activity of refractory vasculo-Behçet disease (vasculo-BD. However, it is completely unknown whether we can discontinue anti-TNF-α agents under clinical remission. A 31-year-old patient with vasculo-BD was initially treated with a high dose of steroid and intravenous cyclophosphamide therapy. Six months later, however, the disease recurred. IFX was administered and immediately the disease activity was reduced. Fortunately, we could discontinue IFX after 18-month remission and no recurrence has been observed. Based on previous reports and our patient, all patients who could discontinue IFX sustained clinical remission for at least one year, continued taking immunosuppressive agents such as methotrexate and azathioprine, and had vascular involvements only in non-life-threatening major vessels such as leg or arm arteries/veins. This is a report suggesting the possibility of discontinuation of IFX in vasculo-BD.

  19. [Acute severe ulcerative colitis treated with accelerated infliximab induction. Case report].

    Science.gov (United States)

    Fluxá, Daniela; Flores, Lilian; Kronberg, Udo; Moreno, Mauricio; Figueroa, Carolina; Ibáñez, Patricio; Lubascher, Jaime; Simian, Daniela; Quera, Rodrigo

    2017-08-01

    Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

  20. Mucosal healing of Crohn's disease in a patient with concurrent systemic lupus erythematosus using infliximab.

    Science.gov (United States)

    Kagaya, Yuka; Sakamoto, Hirotsugu; Yano, Tomonori; Sunada, Keijiro; Lefor, Alan Kawarai; Niki, Toshiro; Yamamoto, Hironori

    2017-06-01

    We describe a patient with Crohn's disease (CD) concurrent with systemic lupus erythematosus (SLE). Continuous prednisolone and cyclosporine treatment resulted in no recurrent symptoms. However, diarrhea, vomiting, and fever occurred for approximately 3 months. A colonoscopy was then performed, which showed a discontinuous cobblestone appearance and longitudinal ulcers extending from the sigmoid colon to the descending colon and distal ileum. A biopsy revealed a noncaseating granulomatous lesion in the colonic mucosa. These findings led to a diagnosis of CD concurrent with SLE. We first attempted treatment with a full elemental diet, mesalazine, and azathioprine, in that order. However, as there was no improvement in inflammation, we started infliximab, a tumor necrosis factor-alpha inhibitor. Transanal double-balloon enteroscopy performed 4 months after starting infliximab showed mucosal healing, suggesting that infliximab was effective. There are few reports of treating patients with CD concurrent with SLE using a tumor necrosis factor-alpha inhibitor. We report our experience with a patient who had mucosal healing with infliximab and review the literature.

  1. Disease duration and age influence CARD15 expression in Crohn's disease.

    Science.gov (United States)

    Poniewierka, Elżbieta; Neubauer, Katarzyna; Kempiński, Radosław; Sadakierska-Chudy, Anna

    2016-01-05

    One of the susceptibility genes in Crohn's disease (CD) is CARD15. Our study examined the relationship between peripheral CARD15 expression and phenotype and duration of CD, treatment methods and inflammatory indices. Sixty patients with CD and 30 healthy volunteers as controls were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) with E.Z.N.A. Total RNA Kit (Omega Bio-tek) then quantitative real-time PCR was performed on the ABI Prism 7900 HT Real-Time PCR System. CARD15 gene expression in PBMCs in CD was significantly higher than in the control group. The highest level of gene expression was found in CD patients in the fourth decade of life. The mRNA level of the CARD15 gene was higher in patients with disease duration between 12 and 60 months. A positive correlation was found between erythrocyte sedimentation rate (ESR) and gene expression level. Gene expression increased with increasing level of C-reactive protein and ESR, but it was not statistically significant. CARD15 expression significantly decreased in CD patients treated with anti-TNFα agents compared to azathioprine or steroid treatment groups. Expression of the CARD15 gene in Crohn›s disease is higher than in healthy individuals. Disease duration and age of patients seem to be the most important factors influencing CARD15 expression.

  2. Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link

    Directory of Open Access Journals (Sweden)

    Francesco Tovoli

    2010-10-01

    Full Text Available Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.

  3. Therapeutic relevance of HRCT findings from a pneumological viewpoint; Therapeutische Relevanz des HRCT-Befundes aus pneumologischer Sicht

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    Suchy, R. [Klinik Donaustauf, Zentrum fuer Pneumologie, Donaustauf (Germany); Pfeifer, M. [Klinik Donaustauf, Universitaetsklinikum Regensburg, Krankenhaus Barmherzige Brueder Regensburg, Donaustauf (Germany)

    2014-12-15

    The high-resolution computed tomography (HRCT) technique is an essential component in diagnosing interstitial lung disease (ILD) as it provides important and specialized information and a much greater accuracy than chest X-rays. It contributes to a narrowing down of the differential diagnoses and is also important for planning further invasive investigations, e.g. bronchoscopy, bronchoalveolar lavage, transbronchial lung biopsy and surgical lung biopsy, if needed. An accurate diagnosis of ILD is based on a multidisciplinary discussion involving pulmonologists, radiologists and pathologists experienced in the diagnosis of ILD. The therapy approaches of five different entities of ILD are shown as examples. In hypersensitivity pneumonitis the mainstay of treatment is complete avoidance of exposure to the provoking antigen. In cryptogenic organizing pneumonia most patients recover with corticosteroid therapy with prednisolone over a period of 6 months to 1 year. In cases of sarcoidosis therapy depends on organ involvement and functional impairment but there is no durable benefit to routine treatment of patients with acute pulmonary sarcoidosis, even among those with stage II or III chest radiographs. In general, patients with severe or progressive disease will require treatment. In idiopathic pulmonary fibrosis (IPF) a confident radiological diagnosis of definitive usual interstitial pneumonia (UIP) obviates the need for surgical lung biopsy. Other etiologies of a HRCT pattern of UIP, such as domestic and occupational environmental exposure, connective tissue disease and drug toxicity must be ruled out. In IPF antifibrotic therapy with pirfenidone (approval since 2011) or the triple tyrosine kinase inhibitor nintendanib (pending approval in 2015) can reduce disease progression but therapy with acetylcysteine alone or in combination with prednisolone and azathioprine failed to meet efficacy endpoints. In the management of scleroderma associated ILD rapid

  4. Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

    Science.gov (United States)

    Hacohen, Yael; Wong, Yu Yi; Lechner, Christian; Jurynczyk, Maciej; Wright, Sukhvir; Konuskan, Bahadir; Kalser, Judith; Poulat, Anne Lise; Maurey, Helene; Ganelin-Cohen, Esther; Wassmer, Evangeline; Hemingway, Chery; Forsyth, Rob; Hennes, Eva Maria; Leite, M Isabel; Ciccarelli, Olga; Anlar, Banu; Hintzen, Rogier; Marignier, Romain; Palace, Jacqueline; Baumann, Matthias; Rostásy, Kevin; Neuteboom, Rinze; Deiva, Kumaran; Lim, Ming

    2018-04-01

    .0 with azathioprine (n = 20, P < .001), 1.79 to 0.52 with mycophenolate mofetil (n = 15, P = .003), and 2.12 to 0.67 with rituximab (n = 9, P < .001), although the median EDSS score remained unchanged. An improvement in ARR (from 2.16 to 0.51, P < .001) and EDSS score (from 2.2 to 1.2, P = .01) was observed in the 12 patients treated with regular intravenous immunoglobulins. Although commonly used to treat patients with multiple sclerosis, DMDs were not associated with clinical improvement in children with MOG-Ab-associated disease, whereas azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were associated with a reduction in relapse frequency. A correct diagnosis of relapsing MOG-Ab-associated disorders is therefore important to optimize immune treatment.

  5. Invasive fungal infections in Argentine patients with systemic lupus erythematosus.

    Science.gov (United States)

    Vinicki, J P; Catalan Pellet, S; Pappalardo, C; Cruzat, V C; Spinetto, M A; Dubinsky, D; Tiraboschi, I N; Laborde, H A; Nasswetter, G

    2013-08-01

    association with leukopenia, lymphopenia, hypocomplementemia, hypogammaglobulinemia or anti-DNA positivity; neither with meprednisone doses >20 mg/day or intravenous methylprednisolone pulse therapy before fungal infection. The use of immunosuppressive therapy with azathioprine showed a significant association (p = 0.017). Cyclophosphamide (p = 0.100) or mycophenolate mofetil (p = 0.256) did not show similar results. The frequency of IFI in hospitalized SLE patients in our hospital was 4.8%. Cryptococcus neoformans was the most common etiologic agent and was primarily responsible for the deaths in this cohort. These data are consistent with publications in East Asia rather than North America where Candida spp. is more common. Unlike other publications, previous immunosuppression with azathioprine was the only risk factor associated with the development of the infection. Invasive fungal infection should be suspected in hospitalized patients with SLE and immunosuppression with CNS or atypical cutaneous manifestation of SLE in order to start appropriate treatment early and obtain better outcome.

  6. AUTOIMMUNE HEPATITIS

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    Yusri Dianne Jurnalis

    2010-05-01

    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  7. Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn disease.

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    Kierkuś, Jarosław; Iwańczak, Barbara; Wegner, Agnieszka; Dadalski, Maciej; Grzybowska-Chlebowczyk, Urszula; Łazowska, Izabella; Maślana, Jolanta; Toporowska-Kowalska, Ewa; Czaja-Bulsa, Grażyna; Mierzwa, Grażyna; Korczowski, Bartosz; Czkwianianc, Elżbieta; Żabka, Alicja; Szymańska, Edyta; Krzesiek, Elżbieta; Więcek, Sabina; Sładek, Małgorzata

    2015-05-01

    The aim of the present study was to compare the efficacy and safety of 2 protocols of maintenance therapy with infliximab (IFX) and an immunomodulatory agent in pediatric patients with Crohn disease (CD): withdrawal of immunomodulators versus continuation of immunosuppressants. The present multicenter randomized open-label trial included 99 patients with CD (ages 14.5 ± 2.6 years) who were administered IFX (5 mg/kg body weight) along with an immunomodulatory agent (azathioprine 1.5-3 mg/kg body weight per day, methotrexate 10-25 mg/week). After 10 weeks of the induction therapy, 84 responders were centrally randomized into 1 of the following groups: group I (n = 45) in which IFX and an immunomodulatory agent were continued up to week 54 and group II (n = 39) in which the immunomodulatory agent was discontinued after 26 weeks. The induction therapy was reflected by a significant decrease in Pediatric Crohn's Disease Activity Index (PCDAI) and Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) values. After the maintenance phase, the analyzed groups did not differ significantly in terms of the clinical response loss rates and final PCDAI and SES-CD scores. Furthermore, no significant intragroup differences were documented between mean PCDAI scores determined at the end of induction and maintenance phases. Intensification/modification of the treatment was required in 13 of 45 (29%) and 11 of 39 (28%) patients of groups I and II, respectively. A total of 9 serious adverse events were documented; none of the patients died during the trial. Twenty-six weeks likely represent the safe duration of combined IFX/immunomodulatory therapy in our sample of pediatric patients with CD.

  8. Update on the diagnosis and management of Behçet’s disease

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    Rokutanda R

    2014-12-01

    Full Text Available Ryo Rokutanda, Mitsumasa Kishimoto, Masato Okada Immuno-Rheumatology Center, St Luke’s International Hospital, Tokyo, Japan Abstract: Behçet’s disease is a multi-organ disorder that is more common in countries around the Silk Road, and manifests as mucosal ulcers and skin lesions, and with ocular involvement. As a systemic disease, it can also involve gastrointestinal organs and the central nervous or cardiovascular systems. Although the etiology of Behçet's disease is not clearly identified, the pathogenesis of the disease is most commonly hypothesized as a profound inflammatory response triggered by an infectious agent in a genetically susceptible host. As there are no single specific manifestations or specific diagnostic tests, various diagnostic criteria have been proposed around the world, and, among them, the International Study Group criteria have been most commonly used. As the clinical expression of Behçet's disease is heterogeneous, the treatment should be individualized based on involved organs, severity of the disease, and patient's background. The choice of therapeutic agents is limited by lack of clinical trials and is based largely on case reports, case series, and several open-label clinical trials. Corticosteroids, colchicine, and traditional immunosuppressive agents, including azathioprine and cyclosporine, have been used for the treatment of Behçet’s disease. Recently, tumor necrosis factor (TNF inhibitors have become available for several rheumatic diseases, and considerable published data suggest that TNF inhibitors represent an important therapeutic advance for patients with severe and resistant disease, as well as for those with contraindications or intolerance to these treatments. Keywords: Behçet’s disease, therapeutic agents, etiology, diagnosis

  9. Livebirth after uterus transplantation.

    Science.gov (United States)

    Brännström, Mats; Johannesson, Liza; Bokström, Hans; Kvarnström, Niclas; Mölne, Johan; Dahm-Kähler, Pernilla; Enskog, Anders; Milenkovic, Milan; Ekberg, Jana; Diaz-Garcia, Cesar; Gäbel, Markus; Hanafy, Ash; Hagberg, Henrik; Olausson, Michael; Nilsson, Lars

    2015-02-14

    Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. Jane and

  10. Management of Pemphigus Vulgaris.

    Science.gov (United States)

    Cholera, Mimansa; Chainani-Wu, Nita

    2016-06-01

    Pemphigus vulgaris (PV) is a chronic, autoimmune, vesiculobullous disease. As a result of the relative rarity of PV, published randomized controlled trials (RCTs) are limited, which makes it difficult to evaluate the efficacy of different treatment regimens in this disease. This also precludes conduct of a meta-analysis. English-language publications describing treatment outcomes of patients with PV were identified by searches of electronic databases through May 2015, and additionally by review of the bibliography of these publications. A total of 89 papers, which included 21 case reports, 47 case series, 8 RCTs, and 13 observational studies, were identified. The findings from these publications, including information on disease course and prognosis, medications used, treatment responses, and side effects, are summarized in the tables and text of this review. Prior to availability of corticosteroid therapy, PV had a high fatality rate. Early publications from the 1970s reported high-dose, prolonged corticosteroid use and significant associated side effects. Later reports described use of corticosteroids along with steroid-sparing adjuvants, which allows a reduction in the total dose of corticosteroids and a reduction in observed mortality and morbidity. For the majority of patients in these reports, a long-term course on medications lasting about 5-10 years was observed; however, subgroups of patients requiring shorter courses or needing longer-term therapy have also been described. Early diagnosis of PV and early initiation of treatment were prognostic factors. In recent publications, commonly used initial regimens include corticosteroids in combination with mycophenolate or azathioprine; whereas, for patients with inadequate response to these regimens, adjuvants such as intravenous immunoglobulin (IVIg) or rituximab are used. The review findings emphasize the importance of early diagnosis, early initiation of treatment, and use of steroid-sparing adjuvants to

  11. Pemphigus vulgaris: an evidence-based treatment update.

    Science.gov (United States)

    Zhao, Cathy Y; Murrell, Dedee F

    2015-02-01

    While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established. The objective of this systematic review is to assess the literature on the efficacy and safety of interventions for the treatment of pemphigus vulgaris. Five electronic databases were searched, including The Cochrane Skin Group's Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE and Latin American and Caribbean Health science Information database (LILACS). Five trial registers as well as reference lists of included RCTs were also searched. Any published randomised controlled trial (RCT) on intervention for pemphigus vulgaris was included, provided the diagnosis of pemphigus vulgaris was confirmed with appropriate clinical features, histopathology and immunofluorescence studies. Studies which included forms of pemphigus other than pemphigus vulgaris were excluded. Altogether 18 RCTs were identified including 16 distinct interventions. Included studies were assessed for patient selection, methods of randomisation, blinding, follow-up and selective reporting. Current evidence is incomplete and inconclusive. The interventions which appear promising, but will require further evaluation include adjuvant mycophenolate mofetil (MMF), azathioprine, intravenous immunoglobulins (IVIG), sulfasalazine and pentoxifylline, infliximab, epidermal growth factor and pimecrolimus. Interventions with inconclusive evidence include high (120-180 mg) versus low (45-60 mg) prednisone dosage, pulsed dexamethasone, cyclophosphamide, dexamethasone-cyclophosphamide pulse therapy (DCP), cyclosporine, dapsone, etanercept, acyclovir and tacrolimus. Our review is limited by the small number of high-quality RCTs and variety of outcome measures, precluding the performing of a meta-analysis. The optimal treatment strategy for pemphigus vulgaris remains unclear. Higher quality RCTs are required in the future to re

  12. Prognostic factors of pemphigus vulgaris disease: a study on 119 patients

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    Halaji Z

    2009-03-01

    Full Text Available "nBackground: Since the systemic steroids are introduced in Pemphigus Vulgaris treatment, the prognosis of disease improved significantly. This study was designed to evaluate determining factors in the prognosis of pemphigus vulgaris in Iranian patients. "nMethods: In this study, 119 patients with documented pemphigus vulgaris who had presented to Razi Hospital from 2001 until 2003 were included. These patients had presented for the first time and treated with prednisolone and Azathioprine. Morality rate, minor and major relapses and duration of first remission had been defined as prognostic criteria and correlation between them and other demographic variables and disease characteristics were investigated. "nResults: The majority of patients (84.1% were followed for more than one year. The major recurrence and minor recurrence occurred in 28(23.5% and 65(54.6% of patients respectively, no case of mortality was observed. In patients who received treatment six months or less after onset of disease the frequency of major recurrence was less than the others. 18(17.8% vs. 12(41.4%, (p=0.009. Duration of primary remission more than one year was detected in most of the patients (64.7%. In patients with less than 10 initial cutaneous lesions, period of primary remission was longer than the other patients. (p=0.009. Shorter duration of primary remission were noted in older patients (age>50 in comparison with younger patients (age≤50, p=0.04. "nConclusions: Male gender, old age, interval more than 6 months between onsets of symptoms to initial treatment and more than 10 skin lesions on admission, are associated with poor prognosis of pemphigus vulgaris.

  13. The effect of conventional immunosuppressive therapy on cytokine serum levels in pemphigus vulgaris patients.

    Science.gov (United States)

    Mortazavi, Hossein; Esmaili, Nafiseh; Khezri, Somayeh; Khamesipour, Ali; Vasheghani Farahani, Iman; Daneshpazhooh, Maryam; Rezaei, Nima

    2014-06-01

    Pemphigus vulgaris is an autoimmune disease, in which the role of Th17 cytokines needs to be further explored. This study was performed to assess serum levels of three interleukins (IL) required for Th17 differentiation (IL-1β, IL-6 and IL-23) and two specific Th17 cytokines (IL-17 and IL-22) in a group of patients with pemphigus vulgaris, at baseline, 3 weeks and 6 months after treatment. Correlations between anti-desmogleins and cytokines with disease severity as well as the influence of therapy on the above factors were assessed. Forty-three first-admitted pemphigus vulgaris patients with the active disease entered the study, but only 31 completed the study. Forty-five healthy volunteers were recruited as a control group. The patients were treated with conventional immunosuppressive therapy (oral prednisolone and azathioprine). Cytokines and anti-desmogleins were measured, using enzyme-linked immunosorbent assay. General linear model was used to evaluate the changes over time. In patients at baseline, mean serum level of IL-6 was higher, while mean levels of IL-1β and IL-22 were lower than the controls. After 3 weeks of therapy, IL-1β and IL-6 levels showed a decreasing trend, whereas IL-22 showed an increasing trend. Mean anti-desmogleins 1 and 3 values decreased significantly during the time. Anti-desmoglein values were significantly correlated with disease severity. In conclusion, IL-1β and IL-6 could be involved in the pathogenesis of pemphigus vulgaris. The positive trend of IL-22 is a new finding and should be confirmed by further studies.

  14. Angioedema adquirido autoimune de difícil controle em paciente com lúpus eritematoso sistêmico Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus

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    Vilson Furlanetto Junior

    2010-02-01

    Full Text Available O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.Acquired angioedema is caused by different drugs and lymphoproliferative diseases, and rarely it has also been related to the presence of auto-immune disorders. We report the case of a 47 year old female with systemic lupus erythematosus (SLE and severe cutaneous involvement who developed recurrent localized angioedema of the face, including lips and eye lids, upper limbs, and thorax, not associated with urticaria, and with reduced levels of C1 esterase inhibitor. Treatment with antimalarials, glucocorticoids, and pulse therapy with methylprednisolone associated with azathioprine did not improve her condition. The patient was also unsuccessfully treated with danazol, and she only showed clinical response after several sessions of plasmapheresis, including resolution of the extensive edema of the gastrointestinal tract.

  15. A case of polyarteritis nodosa limited to the right calf muscles, fascia, and skin: a case report

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    Brett Francesca

    2011-09-01

    Full Text Available Abstract Introduction Limited polyarteritis nodosa is a rare benign disease that usually responds well to systemic corticosteroid treatment. We report a case limited to calf muscles, fascia, and skin treated with local corticosteroid therapy directed to the affected areas by ultrasound guidance. Case presentation A 36-year-old Caucasian woman presented with a 10-month history of progressive right calf pain and swelling, which were unresponsive to treatment with non-steroidal anti-inflammatory drugs and physiotherapy. An examination revealed a swollen tender right calf with indurated overlying skin. Laboratory investigations showed an erythrocyte sedimentation rate of 24 mm/hour and a C-reactive protein of 15 mg/dl. Full blood count, renal profile, and creatinine kinase level were normal. A full autoantibody screen and hepatitis B and C serology results were negative. A chest X-ray was unremarkable. Magnetic resonance imaging of the right leg revealed increased signal intensity in T2-weighted images and this was suggestive of extensive inflammatory changes of the gastrocnemius muscle and, to a lesser extent, the soleus muscle. There were marked inflammatory changes throughout the gastrocnemius muscle and the subcutaneous tissue circumferentially around the right lower leg. A biopsy of affected skin, muscle, and fascia showed histopathological features consistent with polyarteritis nodosa, including small-vessel vasculitis with fibrinoid changes in the vessel wall and intense perivascular and focal mural chronic inflammatory changes. Our patient declined treatment with oral steroids. She received a course of ultrasound-guided injections of steroid (Depo-Medrone, methylprednisolone in the involved muscle area and commenced maintenance azathioprine with a good response. Conclusions Limited polyarteritis nodosa is rare and affects middle-aged individuals. In most cases, treatment with moderate- to high-dose corticosteroids gives symptomatic relief

  16. Pharmacology of drugs for hyperuricemia. Mechanisms, kinetics and interactions.

    Science.gov (United States)

    Pea, F

    2005-01-01

    The pharmacological profile of drugs for hyperuricemia is reviewed. These agents may reduce the amount of uric acid in blood by means of two different ways: (1) by reducing uric acid production through the inhibition of the enzyme xanthine oxidase (as allopurinol); (2) by increasing uric acid clearance through an inhibition of its renal tubular reabsorption (as probenecid), or through its metabolic conversion to a more soluble compound (as urate oxidase). Allopurinol is rapidly converted in the body to the active metabolite oxypurinol whose total body exposure may be 20-fold greater than that of the parent compound due to a much longer elimination half-life. Allopurinol undergoes several pharmacokinetic interactions with concomitant administered drugs, some of which may be potentially hazardous (especially with mercaptopurine and azathioprine). Probenecid is an uricosuric agent which undergoes extensive hepatic metabolism and whose elimination after high doses may become dose dependent. It may inhibit renal tubular secretion of several coadministered agents, including methotrexate and sulphonylureas. Rasburicase is a recombinant form of the enzyme urate oxidase which catalyzes the conversion of uric acid to the more soluble compound allantoin. Unlike allopurinol, it does not promote accumulation of hypoxanthine and xanthine in plasma, thus preventing the risk of xanthine nephropathy. Rasburicase showed no significant accumulation in children after administration of either 0.15 or 0.20 mg/kg/daily for 5 days. Rasburicase probably undergoes peptide hydrolysis and in in vitro studies was shown neither to inhibit or induce cytochrome P450 isoenzymes nor to interact with several drugs, so that no relevant interaction is expected during cotreatment in patients.

  17. Autoantibodies other than anti-desmogleins in pemphigus vulgaris patients

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    Marwah Adly Saleh

    2017-01-01

    Full Text Available Background: Pemphigus vulgaris (PV is an immunoglobulin G-mediated autoimmune bullous skin disease. Nonorgan-specific antibodies were detected in Tunisian and Brazilian pemphigus patients with different prevalence. Materials and Methods: Fifty PV patients and fifty controls were screened for antinuclear antibodies (ANAs, anti-smooth muscle antibodies (ASMAs, anti-parietal antibodies (APAs, anti-mitochondrial antibodies, and Anti-nuclear cytoplasmic antibodies (ANCA by indirect immunofluorescence. Results: Thirty-nine patients were female and 11 were male. Fifteen patients did not receive treatment before while 35 patients were on systemic steroid treatment ± azathioprine. Twenty (40% of the PV patients and 1 (2% control had positive ANA. ANA was significantly higher in PV patients than controls, P< 0.0001. ASMAs were detected in 20 (40% PV patients and none of the controls. ASMA was significantly higher in PV patients than controls, P< 0.0001. No significant difference was detected between treated and untreated regarding ANA, P - 0.11. However, there was a significant difference between treated and untreated regarding ASMA, P- 0.03. Six patients (12% and none of the controls had positive APA. There was a significant difference between the patients and the controls in APA. P- 0.027. Conclusion: Egyptian PV patients showed more prevalent ANA, ASMA, and APA than normal controls. Follow-up of those patients is essential to detect the early development of concomitant autoimmune disease. Environmental factors might account for the variability of the nonorgan-specific antibodies among different populations.

  18. Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function*

    Science.gov (United States)

    Shin, Jin-Young; Wey, Michael; Umutesi, Hope G.; Sun, Xiangle; Simecka, Jerry; Heo, Jongyun

    2016-01-01

    6-Thiopurine (6-TP) prodrugs include 6-thioguanine and azathioprine. Both are widely used to treat autoimmune disorders and certain cancers. This study showed that a 6-thioguanosine triphosphate (6-TGTP), converted in T-cells from 6-TP, targets Rac1 to form a disulfide adduct between 6-TGTP and the redox-sensitive GXXXXGK(S/T)C motif of Rac1. This study also showed that, despite the conservation of the catalytic activity of RhoGAP (Rho-specific GAP) on the 6-TGTP-Rac1 adduct to produce the biologically inactive 6-thioguanosine diphosphate (6-TGDP)-Rac1 adduct, RhoGEF (Rho-specific GEF) cannot exchange the 6-TGDP adducted on Rac1 with free guanine nucleotide. The biologically inactive 6-TGDP-Rac1 adduct accumulates in cells because of the ongoing combined actions of RhoGEF and RhoGAP. Because other Rho GTPases, such as RhoA and Cdc42, also possess the GXXXXGK(S/T)C motif, the proposed mechanism for the inactivation of Rac1 also applies to RhoA and Cdc42. However, previous studies have shown that CD3/CD28-stimulated T-cells contain more activated Rac1 than other Rho GTPases such as RhoA and Cdc42. Accordingly, Rac1 is the main target of 6-TP in activated T-cells. This explains the T-cell-specific Rac1-targeting therapeutic action of 6-TP that suppresses the immune response. This proposed mechanism for the action of 6-TP on Rac1 performs a critical role in demonstrating the capability to design a Rac1-targeting chemotherapeutic agent(s) for autoimmune disorders. Nevertheless, the results also suggest that the targeting action of other Rho GTPases in other organ cells, such as RhoA in vascular cells, may be linked to cytotoxicities because RhoA plays a key role in vasculature functions. PMID:27189938

  19. Stevens-Johnson syndrome and toxic epidermal necrolysis in childhood-onset systemic lupus erythematosus patients: a multicenter study

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    Ana Paula Sakamoto

    2017-07-01

    Full Text Available Objective: To assess Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN in a large population of childhood-onset systemic lupus erythematosus (cSLE patients. Methods: Multicenter study including 852 cSLE patients followed in Pediatric Rheumatology centers in São Paulo, Brazil. SJS was defined as epidermal detachment below 10% of body surface area (BSA, overlap SJS-TEN 10-30% and TEN greater than 30% of BSA. Results: SJS and TEN was observed in 5/852 (0.6% cSLE female patients, three patients were classified as SJS and two patients were classified as overlap SJS-TEN; TEN was not observed. The mean duration of SJS and overlap SJS-TEN was 15 days (range 7-22 and antibiotics induced four cases. Regarding extra-cutaneous manifestations, hepatomegaly was observed in two cSLE patients, nephritis in two and neuropsychiatric involvement and conjunctivitis were observed respectively in one patient. Hematological involvement included lymphopenia in four, leucopenia in three and thrombocytopenia in two patients. The mean SLEDAI-2K score was 14.8 (range 6-30. Laboratory analysis showed low C3, C4 and/or CH50 in two patients and the presence of anti-dsDNA autoantibody in two patients. One patient had lupus anticoagulant and another one had anticardiolipin IgG. All patients were treated with steroids and four needed additional treatment such as intravenous immunoglobulin in two patients, hydroxychloroquine and azathioprine in two and intravenous cyclophosphamide in one patient. Sepsis was observed in three cSLE patients. Two patients required intensive care and death was observed in one patient. Conclusion: Our study identified SJS and overlap SJS-TEN as rare manifestations of active cSLE associated with severe multisystemic disease, with potentially lethal outcome.

  20. Longterm outcomes and damage accrual in patients with childhood systemic lupus erythematosus with psychosis and severe cognitive dysfunction.

    Science.gov (United States)

    Lim, Lily Siok Hoon; Lefebvre, Arlette; Benseler, Susanne; Silverman, Earl D

    2013-04-01

    (1) To describe the clinical course and response to treatment; and (2) to evaluate and compare damage accrual of distinct phenotypic subgroups of patients with clinically important psychiatric illness of pediatric systemic lupus erythematosus (pSLE). A single-center cohort study of patients with pSLE followed at a pediatric lupus clinic from 1985 to July 2009. Clinical course and response to treatment were studied. Remission was defined by absence of psychiatric/cognitive symptoms while receiving minimal doses of prednisone. Disease activity and damage were measured using SLE Disease Activity Index and SLE Damage Index. Fifty-three children were included: 40 with psychosis and cognitive dysfunction (PSYC group) and 13 with isolated cognitive dysfunction (COG group). All received immunosuppressive treatment. Eighteen of 32 treated with azathioprine required a change to cyclophosphamide for poor response but none on cyclophosphamide required a change. The median times to remission were 72 weeks (PSYC) and 70 weeks (COG). Eight patients (7 PSYC, 1 COG) experienced flare following response/remission. New damage was noted in 50% of children at a median of 11 months: 57% of PSYC group, 31% of COG group. Persistent cognitive dysfunction was seen in 16% of PSYC patients and 15% of COG patients. Most patients responded to immunosuppressive treatment, although median time to remission was > 1 year. Roughly half the patients acquired a new damage item, most of which did not interfere with functional abilities. Fewer than 20% of patients developed neuropsychiatric damage. Both phenotypes of psychiatric pSLE responded equally well to current treatment.

  1. Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases.

    Science.gov (United States)

    Morel, N; Bonjour, M; Le Guern, V; Le Jeunne, C; Mouthon, L; Piette, J-C; Costedoat-Chalumeau, N

    2015-12-01

    Pericardial involvement is a frequent manifestation of systemic lupus erythematosus (SLE). Growing evidence suggests that colchicine may be useful for acute or recurrent pericarditis. We report for the first time a series of 10 consecutive cases of SLE with pericarditis treated with colchicine. Inclusion criteria in this retrospective study were diagnosis of SLE, pericarditis and receiving colchicine. We included 10 consecutive cases of SLE with pericarditis treated with colchicine (nine women, mean age at the index pericarditis 35 ± 12 years). Pericarditis was the initial manifestation of SLE for two patients, whereas eight patients had SLE lasting for a median of 2.5 years (15 days to 13 years) and had received prednisone (n = 7, 2-30 mg/d), hydroxychloroquine (n = 7), azathioprine (n = 3), methotrexate (n = 2), and mycophenolate mofetil (n = 1). For six patients, pericarditis was associated with other SLE manifestations. Altogether, colchicine avoided the use (n = 2) or increase in dosage (n = 5) of steroids in seven cases; the increase in steroids dosage was minimal for two patients. Colchicine 1 mg was given for a median of 39 days (10 days to 54 months). Symptoms completely resolved after a median of 2.5 days (1-30 days) after initiation of colchicine. Colchicine was maintained or resumed in six patients to prevent recurrence, with no further relapse. Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up. © The Author(s) 2015.

  2. Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

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    Mora Paolo

    2013-01-01

    Full Text Available Abstract Neuro-Behçet’s disease (NBD involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension; thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet’s disease (BD; the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1. We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases. In 19/53 patients (36%, neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine. Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our

  3. Conversion to sirolimus from cyclosporine may induce nephrotic proteinuria and progressive deterioration of renal function in chronic allograft nephropathy patients.

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    Boratyńska, M; Banasik, M; Watorek, E; Falkiewicz, K; Patrzałek, D; Szyber, P; Klinger, M

    2006-01-01

    Antiproliferative and non-nephrotoxic properties of sirolimus have been exploited for treatment of patients with chronic graft dysfunction. In this paper we point to the possible association of nephrotic syndrome and renal impairment with rapid conversion from cyclosporine (CsA) to sirolimus in patients with chronic nephropathy. Five male patients, ages 34 to 56 years, with chronic renal failure in the course of glomerulonephritis, were transplanted between 1997 and 1999. For the first 49 to 65 months, the immunosuppressive regimen consisted of CsA, azathioprine (AZA), and prednisone. Thereafter, due to chronic nephropathy evidenced by biopsy, conversion to sirolimus was performed with sharp withdrawal of CsA. The serum creatinine level prior to conversion was 1.9 +/- 0.3 mg/dL. Trace to 86 mg/dL proteinuria was found in 3 patients, while 2 patients had about 200 mg/dL. After 2 to 4 months of sirolimus treatment the proteinuria progressed (558 +/- 183 mg/dL); edema, hypoproteinemia, hypoalbuminemia, and hyperlipidemia developed; and the serum creatinine increased to 3.5 +/- 0.8 mg/dL. Biopsies performed in three patients revealed new pathologic changes. After 4 to 5 months, we performed reconversion to calcineurin inhibitor. Proteinuria decreased to 0 to 150 mg/dL; nevertheless the serum creatinine was continuously rising. Six to 15 months after the conversion, 3 patients returned to dialysis. The fourth patient, who was earlier reconverted, has a serum creatinine level of 2.0 mg/dL after 15 months. In conclusion, conversion from CsA to sirolimus may induce nephrotic syndrome with progressive deterioration of renal function. Converted patients require careful monitoring of proteinuria and renal function. Early reconversion to calcineurin inhibitor may prevent progressive deterioration of graft function.

  4. Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville.

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    de Felipe, Beatriz; Olbrich, Peter; Lucenas, José Manuel; Delgado-Pecellin, Carmen; Pavon-Delgado, Antonio; Marquez, Josefina; Salamanca, Carmen; Soler-Palacin, Pere; Gonzalez-Granado, Luis Ignacio; Antolin, Laura Ferreras; Borte, Stephan; Neth, Olaf

    2016-02-01

    Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) improves outcome of affected children. T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) determination from dried blood spots (DBS) identify neonates with severe T- and/or B-lymphopenia. No prospective data exist of the impact of gestational age (GA) and birth weight (BW) on TRECs and KRECs values. TRECs and KRECs determination using triplex RT-PCR (TRECS-KRECS-β-actin-Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut-off levels were TRECs 700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (NBS quality assurance program, CDC) were included. A total of 5160 DBS were tested. Re-punch was needed in 77 samples (1.5%) due to insufficient β-actin (<700 copies/punch). Pre-term neonates (GA<37 weeks) and neonates with a BW<2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeat positive results five neonates were re-called (<0.1%): Fatal chromosomopathy (n = 1; TRECs 1/KRECs 4); extreme pre-maturity (n = 2; TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All internal and external controls were correctly identified. TRECS-KRECS-β-actin-Assay correctly identifies T- and B-cell lymphopenias. Pre-maturity and low BW is associated with lower TREC and KREC levels. Extreme pre-maturity and maternal immune suppressive therapy may be a cause for false positive results of TRECs and KRECs values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

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    Pasadhika S

    2014-02-01

    Full Text Available Sirichai Pasadhika,1 James T Rosenbaum2 1Department of Ophthalmology, Southern Arizona Veterans Administration Health Care System, Tucson, AZ, USA; 2Legacy Devers Eye Institute, Portland, OR, USA Abstract: Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet's disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet's disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present

  6. Results of the conversion to everolimus in renal transplant recipients with posttransplantation malignancies.

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    Chiurchiu, C; Carreño, C A; Schiavelli, R; Petrone, H; Balaguer, C; Trimarchi, H; Pujol, G S; Novoa, P; Acosta, F; González, C; Arriola, M; Massari, P U

    2010-01-01

    Management of posttransplantation malignancies should include control of the neoplasia and preservation of renal function. Conversion to everolimus (EVL) would potentially have both effects. Twenty-one patients were converted to EVL due to posttransplantation neoplasms. We have presented herein descriptive data and postconversion (PC) outcomes among subjects of mean age 53.6 +/- 10.1 years (range, 36-69), 57.1% were males, undergoing conversion at 108.2 +/- 74.7 (range, 5-316) months after transplantation. All patients received standard immunosuppressive therapy and 9.5% had been induced with thymoglobulin. Malignant neoplasms were as follows: skin (n = 7), gynecological (n = 3), gastrointestinal (n = 3), PTLD (n = 2), renal (n = 2), CNS (n = 1), seminoma (n = 1), Kaposi's sarcoma (n = 1), and prostate cancer (n = 1). PC to EVL, calcineurin inhibitors (CNIs) were discontinued in 18 of 19 patients, mycophenolate in 9/12, and azathioprine in 5/7; all patients continued to receive steroids. In 16 patients (79%) tumors were removed. Chemotherapy was performed in 2 patients with PTLD and radiotherapy was performed in 1 patient with prostate cancer. Mean follow-up was 505 days (range, 59-1151); baseline glomerular filtration rate (GFR) was 53.5 +/- 21.6 mL/min versus 48.5 +/- 25.7 mL/min (P = not significant [NS]) at the last control. One patient experienced graft loss at day 744 after conversion due to chronic rejection. Adverse events were observed in 57% of patients and 28% displayed infections; no patient discontinued EVL. There were 2 deaths: 1 due to an infection and the other due to postsurgical complication. No deaths due to cancer progression were observed. The results observed in this series suggested that conversion to EVL for a posttransplantation neoplasm is a valid therapeutic alternative to preserve graft function and control disease progression.

  7. Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2

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    Sanja Perkovic

    2012-09-01

    Full Text Available Aggressive natural killer-cell leukaemia (ANKL is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV and P-glycoprotein (P-gp expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56+ NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2 MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

  8. The management of refractory coeliac disease

    Science.gov (United States)

    2013-01-01

    A significant proportion of patients with coeliac disease are ‘nonresponsive’ to gluten withdrawal. Most cases of nonresponsive coeliac disease are due to persisting gluten ingestion. Refractory coeliac disease (RCD) is currently defined by persistent symptoms and signs of malabsorption after gluten exclusion for 12 months with ongoing intestinal villous atrophy. Primary (without initial response to diet) and secondary (relapse following response to diet) RCD is recognized. RCD is further classified as type I or type II based on the absence or presence of a population of aberrant intestinal lymphocytes. Quality of dietetic advice and support is fundamental, and lack of objective corroboration of gluten exclusion may result in over-identification of RCD I, particularly in those cases with persisting antibody responses. Over-reliance on lymphocyte clonality similarly may result in over-diagnosis of RCD II which requires careful quantification of aberrant lymphocyte populations. Management of RCD should be undertaken in specialist centres. It requires initial intensive dietary supervision, strict gluten exclusion and subsequent re-evaluation. There is currently insufficient evidence to recommend specific treatments. Steroids are often used in both RCD I and II (albeit with little objective evidence of benefit in RCD II), and azathioprine as steroid-sparing therapy in RCD I. There is growing evidence for the use of cladribine in RCD II with autologous stem cell transplantation in nonresponders, but this requires further multicentre evaluation. There remains considerable controversy regarding the diagnosis, treatment and surveillance of RCD: international consensus in these areas is urgently required to facilitate future therapeutic advances. PMID:23556127

  9. Diagnostic Dilemma in a Patient with Jaundice: How to Differentiate between Autoimmune Pancreatitis, Primary Sclerosing Cholangitis and Pancreas Carcinoma

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    Matthias Buechter

    2012-04-01

    Full Text Available A 68-year-old male patient was referred to our institution in May 2011 for a suspected tumor in the pancreatic head with consecutive jaundice. Using magnetic resonance imaging, further differentiation between chronic inflammation and a malignant process was not possible with certainty. Apart from cholestasis, laboratory studies showed increased values for CA 19-9 to 532 U/ml (normal <37 U/ml and hypergammaglobulinemia (immunoglobulin G, IgG of 19.3% (normal 8.0–15.8% with an elevation of the IgG4 subtype to 2,350 mg/l (normal 52–1,250 mg/l. Endoscopic retrograde cholangiopancreatography revealed a prominent stenosis of the distal ductus hepaticus communis caused by pancreatic head swelling and also a bihilar stenosis of the main hepatic bile ducts. Cytology demonstrated inflammatory cells without evidence of malignancy. Under suspicion of autoimmune pancreatitis with IgG4-associated cholangitis, immunosuppressive therapy with steroids and azathioprine was started. Follow-up endoscopic retrograde cholangiopancreatography after 3 months displayed regressive development of the diverse stenoses. Jaundice had disappeared and blood values had returned to normal ranges. Moreover, no tumor of the pancreatic head was present in the magnetic resonance control images. Due to clinical and radiological similarities but a consecutive completely different prognosis and therapy, it is of fundamental importance to differentiate between pancreatic cancer and autoimmune pancreatitis. Especially, determination of serum IgG4 levels and associated bile duct lesions induced by inflammation should clarify the diagnosis of autoimmune pancreatitis and legitimate immunosuppressive therapy.

  10. Detailed features of hematological involvement and medication-induced cytopenia in systemic lupus erythematosus patients: single center results of 221 patients

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    Teke, Hava Üsküdar; Cansu, Döndü Üsküdar; Korkmaz, Cengiz

    2017-01-01

    Objective Systemic lupus erythematosus (SLE) may affect a number of systems, with the hematological system being one of the most common. Our aim is to determine the existence of cytopenia at diagnosis or during follow-up of our SLE patients as well as the associated factors. Material and Methods A cohort of SLE patients that had been followed-up in the Department of Rheumotology from 1998 to 2015 was retrospectively assessed. Clinical and laboratory findings about the patients were recorded. Results Out of 221 patients composing the cohort, cytopenia was already present in 83.3% (n=184) at the time of diagnosis. Anemia was detected in 56.1% (n=124), leukopenia in 28.9% (n=64), lymphopenia in 76% (n=168), neutropenia in 4.5% (n=10), and thrombocytopenia in 17.2% (n=38) of patients. The proportion of patients with cumulative cytopenia was 90% (n=199). Cumulative cytopenia was disease-related in 83.4% (n=166) and medication-related in 16.6% (n=33) of the patients. In cases of drug-induced cytopenia, azathioprine was the most frequently prescribed drug. In patients with cytopenia at the time of diagnosis, erythrocyte sedimentation rates (ESR) were higher, C3 and C4 hypocomplementemia was more prevalent, and they were positive for anti-ds-DNA at a greater proportion (p0.05). Conclusion The most common hematological disorders in SLE patients are lymphopenia and anemia, and patients must be further examined for APS and renal involvement if they suffer cytopenia. PMID:28638678

  11. Use of the tumor necrosis factor-blockers for Crohn's disease.

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    Thomson, Alan B R; Gupta, Milli; Freeman, Hugh J

    2012-09-21

    The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1) for persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy, and when or if TNFB may be weaned and discontinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

  12. Inflammatory Bowel Disease Patients Are at Increased Risk of Invasive Pneumococcal Disease: A Nationwide Danish Cohort Study 1977-2013.

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    Kantsø, Bjørn; Simonsen, Jacob; Hoffmann, Steen; Valentiner-Branth, Palle; Petersen, Andreas Munk; Jess, Tine

    2015-11-01

    Inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are chronic diseases characterized by an inappropriate immune response, which may also increase the risk of infections. We investigated the risk of invasive pneumococcal disease (IPD) before and after diagnosis of IBD in a population-based cohort study. In a cohort of 74,156 IBD patients and 1,482,363 non-IBD controls included and followed during 1977-2013, hazard rate ratios (HRs) for IPD in IBD patients vs. controls were calculated by Cox regression. Within the IBD group, we also calculated the risk according to ever use of specific IBD medications. Next, using conditional logistic regression, we evaluated the odds of IPD prior to IBD diagnosis. The HRs for IPD within the first 6 months after IBD diagnosis were significantly and more than threefold increased and then decreased to a constant level, which for CD was significantly increased (approximately twofold, HR, 1.99; 95% confidence interval (CI), 1.59-2.49) and for UC non-significantly just above 1. IBD medication use including tumor necrosis factor alpha antagonists had limited impact on the risk of IPD, although having ever used azathioprine increased the risk of IPD in patients with UC (HR, 2.38; 95% CI, 1.00-5.67). Up to 4 years prior to IBD diagnosis, the odds ratio for IPD was significantly increased (UC HR, 1.51, 95% CI, 1.05-2.17; CD HR, 1.79, 95% CI, 1.05-3.03). The risk of IPD is significantly increased both before and after diagnosis of IBD, with limited impact of IBD medications. This suggests that the risk of IPD in patients with IBD is related to the underlying altered immune response in these patients.

  13. Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study.

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    Kim, Jae Hak; Cheon, Jae Hee; Hong, Seong Soo; Eun, Chang Soo; Byeon, Jeong-Sik; Hong, Sung Yi; Kim, Bo-Young; Kwon, Soon-Ho; Kim, Seung Won; Han, Dong Soo; Yang, Suk-Kyun; Kim, Won Ho

    2010-01-01

    Myelotoxicity has been shown to be very common in Korean patients with inflammatory bowel disease (IBD) during azathioprine (AZA) or 6-mercaptopurine (6-MP) treatment. The purpose of this study was to investigate the relative risk of the thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genotypes and TPMT activity for the development of leukopenia in Korean IBD patients during AZA/6-MP treatment. We retrospectively analyzed 286 Korean patients with IBD who had been treated with AZA/6-MP for at least 6 months between June 1996 and September 2006. Common TPMT mutations, including TPMT*1, *2, *3A, *3B, and *3C, and ITPA mutations, including 94C>A and IVS2+21A>C, were determined using a high-performance liquid chromatography method. TPMT activity was measured using liquid chromatography with coupled mass spectrometry/mass spectrometry. Leukopenia occurred in 118 cases (41.3%). TPMT *1/*3C was detected in 7 cases (2.4%), and ITPA 94 C>A was detected in 66 cases (23.1%), including 63 heterozygotes (22.1%) and 3 homozygotes (1.0%). The median TPMT activity was 9.3 U/mL (interquartile range 10.4, range 2.1 to 76.2). Cox regression analysis revealed that patients with heterozygous *3C type TPMT had a higher probability of leukopenia than those with wild type TPMT (P=0.02). Patients with intermediate TPMT activity had a lower probability of leukopenia than those with low activity (P=0.01). However, the ITPA genotype did not affect the risk of leukopenia. Our data showed that it could be helpful to examine TPMT genotypes and to measure TPMT activity in Korean patients taking AZA/6-MP to predict the development of leukopenia.

  14. Endolymphatic irradiation in preparation for renal transplantation: a 26-year's follow-up

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    Maria Margarida Galvão

    Full Text Available OBJECTIVE: The aim of the present study was to analyze the long-term evolution of patients submitted to endolymphatic irradiation as a pre-transplant preparation. SETTING: Referral center of university hospital. DESIGN: Case-control study. MAIN OUTCOMES MEASURES: The study was designed to evaluate the incidence of rejection, kidney loss, leukopenia, infection, and graft survival in the group treated (group 1 prior to surgery, compared to a control group (group 2 composed of patients under identical clinical conditions (sex, age, type of donor, immunosuppressive therapy and time of transplant that did not undergo treatment preparation. PATIENTS: Patients were selected from amongst transplantation candidates on a long-term waiting list, some with a high level of antibodies against panel. The control group was chosen from amongst recently transplanted patients. Patients in the treated group received lipoiodine containing 131I with specific activity ranging between 4 and 6 mCu/ml. RESULTS: A significant difference between the two groups was found with regard to the incidence of rejection crises (21.0% in group 1 and 73.6% in group 2; P= 0.003, and the maintenance dose of azathioprine (smaller in group 1; P< 0.01. As to kidney graft loss due to rejection, a tendency to significance could be identified (10.5% in group 1 and 42.1% in group 2; P= 0.063; however, the difference was not significant between the two groups in terms of reversibility of rejection episodes during the first 60 post-transplant days. CONCLUSIONS: The authors concluded that this method, besides being relatively innocuous (there was no compromising of either the thyroid gland or of gonad function and there was no increase in tumor incidence, has an extended immunosuppressive effect, and can be indicated for cadaveric renal allograft recipients, especially those showing high panel reactivity.

  15. Influences of XDH genotype by gene-gene interactions with SUCLA2 for thiopurine-induced leukopenia in Korean patients with Crohn's disease.

    Science.gov (United States)

    Park, Soo-Kyung; Hong, Myunghee; Ye, Byong Duk; Kim, Kyung-Jo; Park, Sang Hyoung; Yang, Dong-Hoon; Hwang, Sung-Wook; Kwak, Min Seob; Lee, Ho-Su; Song, Kyuyoung; Yang, Suk-Kyun

    2016-01-01

    The impact of genetic variation in the thiopurine S-methyltransferase (TPMT) gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH) is the second major contributor to azathioprine breakdown, polymorphisms in XDH have rarely been studied in IBD patients. We aim to access association between XDH variants and thiopurine-induced leukopenia by gene-gene interaction in a Crohn's disease (CD) population. A total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between four XDH variants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia, NUDT15 (p.Arg139Cys), SUCLA2 (p.Ser199Thr), and TPMT *3C were selected for epistasis analysis with the XDH variants. There was no significant association for two variants of XDH and thiopurine-induced leukopenia. In the epistasis analysis, only XDH (p.Asn1109Thr) * SUCLA2 (p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16; p = 0.03]. After genotype stratification, a positive association on the background of SUCLA2 wild-type (199Ser) between the XDH (p.Asn1109Thr) and early leukopenia (OR = 4.39; p = 0.01) was detected. Genes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination of XDH (p.Asn1109Thr) and SUCLA2 (199Ser) on thiopurine-induced leukopenia.

  16. Individualized Neoral doses in pediatric renal transplantation.

    Science.gov (United States)

    García, Y; Muquillaza, P; Valdebenito, S

    2010-01-01

    We propose a model to calculate individualized Neoral doses based on individual oral clearance (CL/F)(i) and AUC((0-12h)) values. The equation proposed by Dr. Ke-Hua Wu (2005), was employed to calculate the CL/F(i) = 28,5 - (1.24*POD) - 0.252*(TBil-11) + 0,188*(Weight o-58) -0,191*(Age-42) - 2,42*INHI - 0,212*(HCT-28), where CI/F = (L/h), POD = postoperative days, Bil.T = total bilirubin level (umol/L), CBW = in kilograms, age = in years, INHI = concurrent metabolic inhibitors present (1) or absence (0), and HCT = hematocrit percentage. The AUC((0-12h)) was calculated from the C(2) value using the equation AUC((0-12h)) = 815,578 + 4,44696*C(2), derived from the linear correlation observed in earlier work at Clinica Las Condes Hospital. The studied population were 30 kidney transplanted children at Luis Calvo Mackenna Hospital, between 2002 and 2006, who were divided into 2 similar groups according to accurate C(2) sampling time collections. The control group 1 was composed of 13 patients of age 9.85 +/- 4 years whose samples were collected correctly. Group 2 was composed of 17 patients of age 10.43 +/- 6 years with 252 C(2) samples, which were obtained at medical control. All patients were under oral treatment with prednisone, azathioprine, nifedipine, and Neoral administered twice day according the weight of the patient and the C(2) level. Relating Neoral administered doses to calculated doses according to the proposed model, the control group showed a linear correlation coefficient r = 0.924; r(2) = 85.4%; (P calculate Neoral doses had a predictive value of 85.0% when C(2) samples were collected correctly.

  17. Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune presynaptic disorder often associated with cancer.

    Science.gov (United States)

    Schoser, Benedikt; Eymard, Bruno; Datt, Joe; Mantegazza, Renato

    2017-09-01

    Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder that is related to the loss of functional P/Q-type voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals. Up to 60% of cases occur as a paraneoplastic disorder (SCLC-LEMS), most commonly in association with small cell lung cancer. The remaining cases have an idiopathic non-tumor etiology but are associated with underlying autoimmune disease (NT-LEMS). Patients with LEMS invariably experience progressive proximal muscle weakness, often accompanied by general fatigue and autonomic symptoms. Some LEMS clinical symptoms overlap with those of other myasthenic syndromes, most commonly myasthenia gravis, which can contribute to misdiagnosis or delayed diagnosis. Prognosis is related to the presence of cancer or autoimmune disease and the severity/distribution of muscle weakness. Cause of death in patients with SCLC-LEMS is typically tumor progression, whereas NT-LEMS does not reduce life expectancy. LEMS diagnosis is supported by a threefold approach: clinical features, electromyography, and anti-VGCC antibody serology. LEMS is a clinically important early indicator of possible cancer; therefore, a LEMS diagnosis should immediately prompt rigorous oncological screening and surveillance. Symptomatic treatment of LEMS typically involves medications that improve neurotransmission (e.g., the potassium channel blocker amifampridine [3,4-diaminopyridine]), with addition of immunosuppressants/modulators (e.g., prednisone plus azathioprine) in individuals with persistent symptoms. Where a tumor is identified, oncological treatment should take priority. It should be remembered, however, that LEMS has a significant impact on a patient's quality of life and ability to perform daily activities, and therefore warrants timely diagnosis and appropriate treatment in and of itself.

  18. Update on the management of chronic eczema: new approaches and emerging treatment options

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    Hobart W Walling

    2010-07-01

    Full Text Available Hobart W Walling1, Brian L Swick21Private Practice of Dermatology, Coralville IA, USA; 2University of Iowa Hospitals and Clinics, Departments of Dermatology and Pathology, Iowa City, IA, USAAbstract: Atopic dermatitis (AD is a common disease with worldwide prevalence, affecting up to 20% of children and 3% of adults. Recent evidence regarding pathogenesis has implicated epidermal barrier defects deriving from filagrin mutations with resulting secondary ­inflammation. In this report, the authors comprehensively review the literature on atopic dermatitis therapy, including topical and systemic options. Most cases of AD will benefit from emollients to enhance the barrier function of skin. Topical corticosteroids are first-line therapy for most cases of AD. Topical calcineurin inhibitors (tacrolimus ointment, pimecrolimus cream are considered second line therapy. Several novel barrier-enhancing prescription creams are also available. Moderate to severe cases inadequately controlled with topical therapy may require phototherapy or systemic therapy. The most commonly employed phototherapy modalites are narrow-band UVB, broadband UVB, and UVA1. Traditional systemic therapies include short-term corticosteroids, cyclosporine (considered to be the gold standard, methotrexate, azathioprine, mycophenolate mofetil, and most recently leflunamide. Biologic therapies include recombinant monoclonal antibodies acting on the immunoglobulin E / interleukin-5 pathway (omalizumab, mepolizumab, acting as tumor necrosis factor-a inhibitors (infliximab, etanercept, adalimumab, and acting as T-cell (alefacept and B-cell (rituxumab inhibitors, as well as interferon γ and intravenous immunoglobulin. Efficacy, safety, and tolerability are reviewed for each medication.Keywords: topical corticosteroids, phototherapy, dermatitis

  19. Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature

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    Invernizzi Pietro

    2012-07-01

    Full Text Available Abstract Background Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH is eminently a paediatric disease. Case presentation We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1 showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF, and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. Conclusion This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.

  20. Second-line Agents in Pediatric Patients With Autoimmune Hepatitis: A Systematic Review and Meta-analysis.

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    Zizzo, Andréanne N; Valentino, Pamela L; Shah, Prakesh S; Kamath, Binita M

    2017-07-01

    Ten percent to 20% of children with autoimmune hepatitis (AIH) require second-line therapy to achieve remission. Although current guidelines exist on first-line management, evidence for second-line therapy in treatment-refractory patients is lacking. Our aim was to perform a systematic review and meta-analysis of the efficacy and safety of second-line treatments used in this population. Electronic and manual searches were used to identify potential studies for inclusion. Studies were selected based on reported response rates to second-line therapies in children who failed response to prednisone and azathioprine. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Meta-analysis using weighted estimate of response rates at 6 months was performed for each treatment option. Heterogeneity was assessed. Fifteen studies of 76 pediatric patients with AIH were included in the review. Overall response rates at 6 months were estimated as 36% for mycophenolate mofetil (MMF) (N = 34, 95% confidence interval [CI] (16-57)), and 50% for tacrolimus (N = 4, 95% CI (0-100%)) and 83% for cyclosporine (N = 15, 95% CI (66%-100%)). Adverse effects were most frequent with cyclosporine (64% experiencing at least 1 adverse effect) followed by tacrolimus (54%) and MMF (48%). Pooled estimates of adverse events were 78% for cyclosporine (95% CI (54%-100%)), 42% for tacrolimus (95% CI (0%-85%)) and 45% for MMF (95% CI (25%-68%)). Sensitivity analyses were not performed due to small sample size. Cyclosporine had the highest response rate at 6 months in children with standard-treatment-refractory AIH; however, it also had the highest rate of adverse events. MMF was the second most efficacious option with a low adverse effect rate.

  1. In Vitro

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    Orquevaux, Pauline; Masseau, Agathe; Le Guern, Véronique; Gayet, Vanessa; Vauthier, Danièle; Guettrot-Imbert, Gaelle; Huong, Du Le Thi; Wechsler, Bertrand; Morel, Nathalie; Cacoub, Patrice; Pennaforte, Jean-Loup; Piette, Jean-Charles; Costedoat-Chalumeau, Nathalie

    2017-05-01

    To compile and assess data about complication and success rates for in vitro fertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse. This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle. Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26-46). The median number of IVF cycles was 2.6 (1-8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported. These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.

  2. Retrospective analysis of the forty-six patients with bullous pemphigoid followed-up in our clinic

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    Serkan Yazıcı

    2016-09-01

    Full Text Available Background and Design: Bullous pemphigoid (BP is an autoimmune disease characterised by widespread itchy plaques and subepithelial blisterings and usually affects the elderly population. Due to the chronic nature of the disease, to prevent the side effects of chronic steroid treatment, adjuvant immunosuppressive (mycophenolate mofetil, azathioprine, methotrexate and anti-inflammatory (tetracycline, nicotinamide, dapsone agents may be used. In this study, we retrospectively evaluated the clinical and demographic characteristics and applied treatments of 46 patients with the diagnosis of BP and compared with literature data. Materials and Methods: We retrospectively evaluated the records of 46 patients who received clinical and histopathological diagnosis of BP and followed up in our clinic between 2006 and 2013. Results: Of the 46 patients, 22 were female and 24 male. The mean age of onset was 69.54 years (range: 18-105. The duration of the lesion ranged from 1 week to 10 months with a median duration of 8 weeks. The most frequent comorbid chronic disease was hypertension detected in 28 (60.8% patients. Only four patients had a history of malignancy before the onset of the disease. Nineteen patients (42% used more than 5 agents for comorbid diseases. Thirty-two patients (69.5% used systemic corticosteroids alone and ten (22% patients needed additional adjuvant therapies. Conclusion: BP is a major cause of morbidity in the elderly population receiving multiple drug treatment. To avoid the side effects of steroid therapy, especially in patients with severe disease, short-term use of additional immunosuppressive agents appears to be safe and effective.

  3. Secondary Loss of Response to Infliximab in Pediatric Crohn Disease: Does It Matter How and When We Start?

    Science.gov (United States)

    Bolia, Rishi; Rosenbaum, Jeremy; Schildkraut, Vered; Hardikar, Winita; Oliver, Mark; Cameron, Donald; Alex, George

    2018-04-01

    A significant proportion of children with Crohn disease develop a secondary loss of response (LOR) to infliximab. Our aim was to study the impact of initial treatment strategies on secondary LOR. We reviewed the medical records of children with Crohn disease who received scheduled maintenance infliximab therapy for at least 12 months. We compared children who developed LOR with those who did not; with regards to their clinical and laboratory parameters, disease phenotype, and treatment strategy before developing LOR. A total of 73 children (median age at diagnosis 11 (2-16) years, 41 boys) who had received a median duration of 33 (13-110) months of infliximab therapy were included in the final analysis. LOR was seen in 25(34.2%). Demographic variables, disease phenotype (age, disease location, and behavior), inflammatory parameters, and pediatric Crohn disease activity index at induction with infliximab were similar between both groups. Children with LOR had a significantly greater number of flares of the disease when compared to those who did not have LOR (4 [1-8] vs 2 [1-5] P = 0.03). The choice of the concomitant immunomodulator-methotrexate (11/29 [37.9%]) versus azathioprine (11/36 [30.5%]) (P = 0.6) did not affect LOR rates. The median time-lag between diagnosis and induction with infliximab was significantly longer in children with LOR as compared to those who did not have an LOR (28 [4-90] months vs 12.5 [1-121] months, P = 0.004). Early use of infliximab in pediatric Crohn disease is associated with a decrease in secondary LOR. The type of concomitant immunomodulator used does not make a difference to LOR rates.

  4. Nrf2 Activation Protects against Solar-Simulated Ultraviolet Radiation in Mice and Humans.

    Science.gov (United States)

    Knatko, Elena V; Ibbotson, Sally H; Zhang, Ying; Higgins, Maureen; Fahey, Jed W; Talalay, Paul; Dawe, Robert S; Ferguson, James; Huang, Jeffrey T-J; Clarke, Rosemary; Zheng, Suqing; Saito, Akira; Kalra, Sukirti; Benedict, Andrea L; Honda, Tadashi; Proby, Charlotte M; Dinkova-Kostova, Albena T

    2015-06-01

    The transcription factor Nrf2 determines the ability to adapt and survive under conditions of electrophilic, oxidative, and inflammatory stress by regulating the expression of elaborate networks comprising nearly 500 genes encoding proteins with versatile cytoprotective functions. In mice, disruption of Nrf2 increases susceptibility to carcinogens and accelerates disease pathogenesis. Paradoxically, Nrf2 is upregulated in established human tumors, but whether this upregulation drives carcinogenesis is not known. Here we show that the incidence, multiplicity, and burden of solar-simulated UV radiation-mediated cutaneous tumors that form in SKH-1 hairless mice in which Nrf2 is genetically constitutively activated are lower than those that arise in their wild-type counterparts. Pharmacologic Nrf2 activation by topical biweekly applications of small (40 nmol) quantities of the potent bis(cyano enone) inducer TBE-31 has a similar protective effect against solar-simulated UV radiation in animals receiving long-term treatment with the immunosuppressive agent azathioprine. Genetic or pharmacologic Nrf2 activation lowers the expression of the pro-inflammatory factors IL6 and IL1β, and COX2 after acute exposure of mice to UV radiation. In healthy human subjects, topical applications of extracts delivering the Nrf2 activator sulforaphane reduced the degree of solar-simulated UV radiation-induced skin erythema, a quantifiable surrogate endpoint for cutaneous damage and skin cancer risk. Collectively, these data show that Nrf2 is not a driver for tumorigenesis even upon exposure to a very potent and complete carcinogen and strongly suggest that the frequent activation of Nrf2 in established human tumors is a marker of metabolic adaptation. ©2015 American Association for Cancer Research.

  5. Einsatz und Wirksamkeit von Systemtherapien bei Erwachsenen mit schwerer Neurodermitis: Erste Ergebnisse des deutschen Neurodermitis-Registers TREATgermany.

    Science.gov (United States)

    Schmitt, Jochen; Abraham, Susanne; Trautmann, Freya; Stephan, Victoria; Fölster-Holst, Regina; Homey, Bernhard; Bieber, Thomas; Novak, Natalija; Sticherling, Michael; Augustin, Matthias; Kleinheinz, Andreas; Elsner, Peter; Weidinger, Stephan; Werfel, Thomas

    2017-01-01

    Versorgungsregister dienen der Erfassung des Einsatzes und der Wirksamkeit von Therapien unter realen Versorgungsbedingungen und sind als Basis einer evidenzbasierten Gesundheitsversorgung unverzichtbar. Das deutsche Neurodermitis-Register TREATgermany wurde als weltweit erstes Register für Patienten mit schwerer Neurodermitis 2011 initiiert. Erwachsene mit schwerer Neurodermitis (aktuelle/frühere antientzündliche Systemtherapie und/oder objektiver SCORAD ≥ 40) werden über einen Zeitraum von 24 Monaten prospektiv beobachtet. Anhand validierter Erhebungsinstrumente werden die klinische Erkrankungsschwere (EASI, SCORAD), Lebensqualität (DLQI), Symptome, globale Erkrankungsschwere sowie die Patientenzufriedenheit erfasst und die durchgeführten Therapien dokumentiert. Die vorliegende Analyse beschreibt die Charakteristika, Therapiewahl und Wirksamkeit der eingesetzten antiinflammatorischen Systemtherapien der bis Oktober 2014 eingeschlossenen Patienten. An fünf Zentren wurden insgesamt 78 Patienten (Durchschnittsalter 39 Jahre, 61 % männlich) eingeschlossen. Bei den Patienten besteht eine hohe Inanspruchnahme ambulanter und stationärer Leistungen. Ciclosporin war das am häufigsten eingesetzte Systemtherapeutikum und zeigte die höchste klinische Effektivität (EASI-50-Ansprechrate 51 %; EASI-75-Ansprechrate 34 % nach zwölfwöchiger Therapie). Azathioprin, Methotrexat (MTX), Prednisolon oral, Mycophenolat, Alitretinoin und Leflunomid wurden ebenfalls bei einzelnen Patienten eingesetzt. Die vorliegende Registerauswertung gibt wichtige Hinweise zur derzeitigen Versorgung von Erwachsenen mit schwerer Neurodermitis in Deutschland, dokumentiert die hohe Erkrankungslast, den Nutzen vorhandener Therapien und den Bedarf an weiteren, effektiven und in der Langzeitanwendung sicheren Therapieoptionen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  6. Lethality of patients with rheumatoid arthritis depending on adalimumab administration: imitation modeling

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    D V Goryachev

    2009-01-01

    Full Text Available Lethality of pts with rheumatoid arthritis (RA exceeds mortality values in general population. Possibility of disease modifying anti-rheumatic drugs (DMARD influence on RA pts lethality has been widely discussed lately in scientific works. Objective. To determine possible lethality diminishment in Russian population of RA pts with one of biological drugs TNFα antagonist adalimumab. Material and methods. Model construction is based on the fact of lethality dependence on pt functional state assessed by HAQ. Model simulating progression of functional disability in pts with RA visiting medical institutions of Russia was made (RAISER study. 3 model variants for imitation of consecutive change of DMARDs including adalimumab were done. First consecution assessed DMARD change in the next chain: adalimumab-methotrexate-sulfasalazine-leflunomide-azathioprine-cyclosporine-palliative therapy. Second consecution: adalimumab administration after failure of first 3 DMARDs. Third consecution considered only change of synthetic DMARDs without adalimumab inclusion. Model imitated participation of 3000 pts in every consecution. Prognosis horizon was 12 years. Age of pts and initial HAQ distribution were get from results of epidemiological RAISER study. Calculation was done on the base of elevation of standardized lethality level (SLL in population of RA pts in average from 135% to 300%. SLL values from 80 to 320% were used depending on functional disability degree with converting to Russian values of age-specific lethality coefficient for 1999. Results. Lethality in treatment consecutions including adalimumab was significantly lower. To the end of 12th year in group not using adalimumab, using it at once and using it after 376 DMARDs respectively 65,1%, 71,6% and 71,1% of pts were still alive. Conclusion. Significant decrease of lethality with adalimumab inclusion in consecution of DMARD change during treatment of RA pts was demonstrated with imitation modeling

  7. Open-Capsule Budesonide for Refractory Celiac Disease.

    Science.gov (United States)

    Mukewar, Saurabh S; Sharma, Ayush; Rubio-Tapia, Alberto; Wu, Tsung-Teh; Jabri, Bana; Murray, Joseph A

    2017-06-01

    Refractory celiac disease (RCD) is a rare condition often associated with poor prognosis. Various immunosuppressive medications (IMs) have been used with modest success. We describe outcomes in patients treated with open-capsule budesonide (OB), including those for whom IM treatment failed. We identified RCD patients treated with OB at Mayo Clinic, Rochester, Minnesota from 2003 to 2015. Demographic, serologic, and clinical variables were analyzed. We identified 57 patients who received OB for suspected RCD. Based on clonal T-cell receptor gamma gene rearrangement or aberrant phenotype of intraepithelial lymphocytes (IELs), 13 patients (23%) were classified as having RCD-2 and 43 (75%) as RCD-1. In one patient (2%) TCR gene rearrangement status was unknown. Most patients were women (69%), mean (s.d.) age was 60.5 (3.5) years and body mass index was 28.4 (4.5) kg/m 2 . The majority had diarrhea (72%), with median of 6 bowel movements per day (range, 4-25). IM treatment (azathioprine, systemic corticosteroids, or regular budesonide) had failed in nearly half. Twenty-four patients (42%) had anemia and 12 (21%) had hypoalbuminemia. All had Marsh 3 lesions on biopsy: 3a (19%), 3b (46%), and 3c (35%). After OB therapy, the majority had clinical (92%) and histologic (89%) improvement. Follow-up biopsy in 7 out of 13 patients with RCD-2 (53%) showed an absence of clonal TCR gamma gene rearrangement/aberrant IEL phenotype previously seen. On follow-up, 2 patients (4%) died of enteropathy-associated T-cell lymphoma. Most patients with RCD show clinical and histopathologic improvement with OB therapy, including those with failure of IMs. OB is a promising therapeutic option for management of RCD.

  8. Wegener granulomatosis (granulomatosis with polyangiitis): evolving concepts in treatment.

    Science.gov (United States)

    Lynch, Joseph P; Tazelaar, Henry

    2011-06-01

    Wegener granulomatosis (WG), the most common of the pulmonary granulomatous vasculitides, typically involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis. THE TERM GRANULOMATOSIS WITH POLYANGIITIS (WEGENER) WAS RECENTLY PROPOSED TO REPLACE THE OLDER TERM, WG. THE TERM GRANULOMATOSIS WITH POLYANGIITIS CAN BE ABBREVIATED TO GPA, WITH THE IDEA THAT THE EPONYM WEGENER WOULD BE OMITTED OVER TIME. Cardinal histologic features include a necrotizing vasculitis involving small vessels, extensive "geographic" necrosis, and granulomatous inflammation. Clinical manifestations of WG are protean; virtually any organ can be involved. The spectrum and severity of the disease are heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis. The pathogenesis of WG has not been elucidated, but both cellular and humoral components are involved. Circulating antibodies against cytoplasmic components of neutrophils [anti-neutrophil cytoplasmic antibodies (c-ANCAs)] likely play a role in the pathogenesis, and often correlate with activity of the disease. Treatment strategies are evolving. Cyclophosphamide (CYC) plus corticosteroids (CSs) is the mainstay of therapy for generalized, multisystemic WG. Historically, the combination of CYC plus CS was used for a minimum of 12 months, but concern about late toxicities associated with CYC has led to novel treatment approaches. Currently, short-course (3 to 6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (e.g., methotrexate, azathioprine) is recommended. Further, methotrexate combined with CS may be adequate for limited, non-life-threatening WG. Recent studies suggest that rituximab may be useful for induction therapy or CYC-refractory WG. The role of other immunomodulatory agents (including trimethoprim-sulfamethoxazole) is also explored. © Thieme Medical

  9. Predictive patterns of early medication adherence in renal transplantation.

    Science.gov (United States)

    Nevins, Thomas E; Robiner, William N; Thomas, William

    2014-10-27

    Patients' adherence with posttransplant immunosuppression is known to affect renal transplant outcomes. Prospectively, individual medication adherence patterns in 195 kidney transplant recipients were quantified with electronic medication monitors. Monitored drugs were mycophenolate mofetil, sirolimus, or azathioprine. Monitoring began at hospital discharge and continued an average of 15±8 months. Patient follow-up for clinical outcomes averaged 8±3 years. Each month's adherence percentage was calculated as the sum of daily adherence percents, divided by the number of evaluable days. During the first 3 months after transplantation, patients (n=44) with declining medication adherence, defined as dropping by 7% or higher (equal to missing 2 days) between months 1 and 2, later experienced lower mean medication adherence for months 6 to 12, 73% versus 92% respectively (Padherence, they also had more frequent (P=0.034) and earlier (P=0.065) acute rejection episodes. This was additionally associated with more frequent (P=0.017) and earlier (P=0.046) death-censored graft loss.In addition, daily medication adherence, expressed as the percentage of doses taken, decreased as the number of prescribed daily doses increased. During the first 3 months after transplantation, adherence with four doses per day averaged 84%, compared to 91% for patients on twice-daily dosing (P=0.024) and 93.5% for patients on once-daily dosing (P=0.008). Early declining medication nonadherence is associated with adverse clinical outcomes. This pattern is detectable during the first 2 months after transplantation. Early detection of nonadherence provides opportunities to target interventions toward patients at the highest risk for adverse behaviors and events.

  10. Risk of hepatobiliary cancer after solid organ transplant in the United States.

    Science.gov (United States)

    Koshiol, Jill; Pawlish, Karen; Goodman, Marc T; McGlynn, Katherine A; Engels, Eric A

    2014-09-01

    Studies of liver cancer risk in recipients of solid organ transplants generally have been small, yielding mixed results, and little is known about biliary tract cancers among transplant recipients. We identified incident hepatobiliary cancers among 201,549 US recipients of solid organs, from 1987 through 2008, by linking data from the US transplant registry with 15 cancer registries. We calculated standardized incidence ratios (SIRs), comparing risk relative to the general population. We also calculated incidence rate ratios (RRs), comparing risk for hepatocellular carcinoma (HCC) and total (intrahepatic and extrahepatic) cholangiocarcinoma among subgroups of recipients. Of transplant recipients, 165 developed hepatobiliary cancers (SIR, 1.2; 95% confidence interval [CI], 1.0-1.4). HCC risk was increased among liver recipients (SIR, 1.5; 95% CI, 1.0-2.2), especially 5 or more years after transplant (SIR, 1.8; 95% CI, 1.0-3.0). Cholangiocarcinoma was increased among liver (SIR, 2.9; 95% CI, 1.6-4.8) and kidney recipients (SIR, 2.1; 95% CI, 1.3-3.1). HCC was associated with hepatitis B virus (RR, 3.2; 95% CI, 1.3-6.9), hepatitis C virus (RR, 10; 95% CI, 5.9-16.9), and non-insulin-dependent diabetes (RR, 2.5; 95% CI, 1.2-4.8). Cholangiocarcinoma was associated with azathioprine maintenance therapy (RR, 2.0; 95% CI, 1.1-3.7). Among liver recipients, primary sclerosing cholangitis was associated with an increased risk of cholangiocarcinoma, compared with the general population (SIR, 21; 95% CI, 8.2-42) and compared with liver recipients without primary sclerosing cholangitis (RR, 12.3; 95% CI, 4.1-36.4). Risks for liver and biliary tract cancer are increased among organ transplant recipients. Risk factors for these cancers include medical conditions and potentially medications taken by recipients. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure.

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    Amira Hosni-Ahmed

    Full Text Available Thiopurine methyltransferase (Tpmt is the primary enzyme responsible for deactivating thiopurine drugs. Thiopurine drugs (i.e., thioguanine [TG], mercaptopurine, azathioprine are commonly used for the treatment of cancer, organ transplant, and autoimmune disorders. Chronic thiopurine therapy has been linked to the development of brain cancer (most commonly astrocytomas, and Tpmt status has been associated with this risk. Therefore, we investigated whether the level of Tpmt protein activity could predict TG-associated cytotoxicity and DNA damage in astrocytic cells. We found that TG induced cytotoxicity in a dose-dependent manner in Tpmt(+/+, Tpmt(+/- and Tpmt(-/- primary mouse astrocytes and that a low Tpmt phenotype predicted significantly higher sensitivity to TG than did a high Tpmt phenotype. We also found that TG exposure induced significantly more DNA damage in the form of single strand breaks (SSBs and double strand breaks (DSBs in primary astrocytes with low Tpmt versus high Tpmt. More interestingly, we found that Tpmt(+/- astrocytes had the highest degree of cytotoxicity and genotoxicity (i.e., IC(50, SSBs and DSBs after TG exposure. We then used human glioma cell lines as model astroglial cells to represent high (T98 and low (A172 Tpmt expressers and found that A172 had the highest degree of cytoxicity and SSBs after TG exposure. When we over-expressed Tpmt in the A172 cell line, we found that TG IC(50 was significantly higher and SSB's were significantly lower as compared to mock transfected cells. This study shows that low Tpmt can lead to greater sensitivity to thiopurine therapy in astroglial cells. When Tpmt deactivation at the germ-line is considered, this study also suggests that heterozygosity may be subject to the greatest genotoxic effects of thiopurine therapy.

  12. Outcome of deceased donor renal transplantation - A single-center experience from developing country

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    Himanshu V Patel

    2013-01-01

    Full Text Available Renal transplantation (RTx is considered as the best therapeutic modality for patient suffering from end-stage renal disease (ESRD. Dearth of donor kidneys is a major problem everywhere, and deceased donor renal transplantation (DDRTx is seen as at least a partial solution. Even so, DDRTx accounts for only less than 4% of RTx in India. We report our 6-year single-center experience on DDRTx vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr, rejection episodes, and delayed graft function (DGF. Between January 2005 and March 2011, 236 DDRTx were performed. Majority of the donors were those with brain death due to road traffic/cerebrovascular accidents. The commonest recipient diseases leading to ESRD were chronic glomerulonephritis (42.8%, diabetes (12.7%, and hypertension (10.6%. Mean recipient age was 36.2 ± 14.2 years; 162 were males and 74 were females. Mean donor age was 45.3 ± 17.13 years; 144 were males and 92 were females. Mean dialysis duration pre-transplantation was 18.5 ± 2.5 months. All recipients received single-dose rabbit-anti-thymocyte globulin induction and steroids, calcinueurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression. Delayed graft function was observed in 29.6% patients and 22% had biopsy-proven acute rejection. Over the mean follow-up of 2.18 ± 1.75 years, patient and graft survival rates were 74.57% and 86.8%, respectively, with mean SCr of 1.42 ± 0.66 mg%. DDRTx achieves acceptable graft function with patient/graft survival, encouraging the use of this approach in view of organ shortage.

  13. Sjögren's syndrome complicated by interstitial cystitis: A case series and literature review.

    Science.gov (United States)

    Darrieutort-Laffite, Christelle; André, Vincent; Hayem, Gilles; Saraux, Alain; Le Guern, Véronique; Le Jeunne, Claire; Puéchal, Xavier

    2015-07-01

    To characterize the interstitial cystitis (IC) associated with Sjögren's syndrome (SS). Report of three new cases. Only cases fulfilling the American-European consensus criteria for SS and the European Society for the Study of Interstitial Cystitis criteria with positive histological findings for IC were included. Thirteen cases of SS and IC have been reported in women, including the three reported here, with a mean age of 54 years. SS appeared first in 77% (n=10) of cases, a mean of 6.6 years before IC. The symptoms of IC included pollakiuria (n=11), lower abdominal pain (n=8), urinary urgency (n=5), painful micturition (n=6), hematuria (n=3) and dysuria (n=3). Urinary dilatation occurred in three cases, leading to acute renal failure in two patients. The diagnosis of IC was confirmed by anatomical evidence of cystitis inflammation on bladder biopsy in all (n=13) patients. Treatment was reported for nine patients, seven of whom (78%) received corticosteroid treatment, which was partially or completely effective in six cases. Immunosuppressive treatment was added in three cases (cyclosporine, n=2; azathioprine, n=1; cyclophosphamide, n=1). Local bladder treatments were performed, with hydraulic distension in five cases and DMSO instillation in one patient. A urinary catheter was inserted in the two cases of acute obstructive renal failure. Urinary symptoms without infection should lead the physician to consider a diagnosis of IC in SS patients. Urinary dilatation may occur, leading to acute obstructive renal failure. Corticosteroid treatment may be effective and local treatments have been tried. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  14. Severe neuro-Behcet’s disease treated with a combination of immunosuppressives and a TNF-inhibitor.

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    Fatma Nur Korkmaz

    2016-10-01

    Full Text Available Abstract/ Resumo Behcet's disease (BD is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD, is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day, iv cylophosphamide (1g and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in

  15. Severe neuro-Behcet's disease treated with a combination of immunosuppressives and a TNF-inhibitor.

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    Korkmaz, Fatma Nur; Ozen, Gulsen; Ünal, Ali Uğur; Kahraman Koytak, Pınar; Tuncer, Nese; Direskeneli, Haner

    2016-01-01

    Abstract/ Resumo Behcet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD), is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI) findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days) and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day), iv cylophosphamide (1g) and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day) and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in NBD. Although

  16. End-stage renal disease in India and Pakistan: incidence, causes, and management.

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    Sakhuja, Vinay; Kohli, Harbir S

    2006-01-01

    Chronic renal failure is a devastating medical, social, and economic problem for patients and their families in India and Pakistan. Reliable data on the true incidence and prevalence of end-stage renal disease (ESRD) in India and Pakistan are lacking because no national registries exist. Among reported cases, chronic glomerulonephritis is the most common cause, accounting for more than one third of patients, while diabetic nephropathy accounts for approximately 20% of all patients in India. Delayed diagnosis and failure to institute measures to slow the progression of renal failure have resulted in a predominantly young ESRD population, with a median age of 44 years. Because of financial constraints, less than one third of all patients referred to a tertiary care center receive any kind of renal replacement therapy. Most hemodialysis patients who stop treatment and die do so because of cost constraints within the first three months, and approximately 5% of patients are started on ambulatory peritoneal dialysis. Renal transplantation is the cheapest option, but < 10% of all patients with ESRD have a transplant. Cyclosporine, azathioprine, and prednisolone continue to be the backbone of post-transplant immunosuppression, but cyclosporine is stopped in a significant proportion of patients at one year post-transplant to cut down costs. Living related donor transplants constitute 70% of all transplants; two thirds of the donors are females, while more than three fourths of all recipients are males. Spouses account for 20% of donors from within families. Almost 30% of transplanted kidneys are donated by living unrelated donors, while cadaver donors account for only 2%. More resources must be mobilized to care for these patients; early detection of renal disease must be facilitated, and measures to delay ESRD must be implemented.

  17. Hashimoto’s Encephalopathy (A Review Article

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    M Ghaffar Pour

    2012-05-01

    Full Text Available

    Background and Objectives

    Hashimoto's encephalopathy (HE known as Steroid Responsive Encephalopathy associated with Autoimmune Thyroditis (SREAT is a rare nervous system disease. HE was originally described by Brain, et. al. in 1966, however its cause still remains unknown after about 40 years. Autoimmune vasculitis of CNS, brain edema, and anti-thyroid antibodies are considered some of the etiologies for HE. It is certain that HE is an autoimmune disease and not a thyroid system disease. HE patients may or may not have goiter.

    Some of the most common neurological manifestations of HE include: Confusion with altered consciousness, seizures, myoloclonus, and cognitive problems. Presence of high titers of anti-thyroid antibodies in blood serum and CSF of HE patients is considered the most common laboratory test for diagnosis of HE. EEG abnormalities such as diffuse slowing and atypical tri-phasic brain waves are the most common findings in about ¾ HE patients. Brain CT-Scan is normal in majority of HE patients. Global or local hypo perfusion may be seen in SPECT scanning of the brain. MRI findings are abnormal in about 40% of HE patients.

    Patients with sub acute or acute onset of confusion, seizure, myoloclonus, stroke-like episodes and amnesia whose laboratory serum and CSF tests indicate presence of high titers of anti- thyroid antibodies should be considered for having HE. Vascular myelopathies, CJD, HSP, Myelinoclastic disease like PML, SSPE, ADE, MS and DNL are some of the differential diagnosis of HE.

    Adrenal corticosteroids are the first line treatment for HE. Recurrent or steroid resistant HE cases may be treated by addition of other immunosuppressant drugs such as  Azathioprine, Cyclophosphamide, or Methotrexate to the 1st line therapy.

  18. Hashimoto’s Encephalopathy (A Review Article

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    M. Ghaffar Pour

    2008-10-01

    Full Text Available Background and ObjectivesHashimoto's encephalopathy (HE known as Steroid Responsive Encephalopathy associated with Autoimmune Thyroditis (SREAT is a rare nervous system disease. HE was originally described by Brain, et. al. in 1966, however its cause still remains unknown after about 40 years. Autoimmune vasculitis of CNS, brain edema, and anti-thyroid antibodies are considered some of the etiologies for HE. It is certain that HE is an autoimmune disease and not a thyroid system disease. HE patients may or may not have goiter. Some of the most common neurological manifestations of HE include: Confusion with altered consciousness, seizures, myoloclonus, and cognitive problems. Presence of high titers of anti-thyroid antibodies in blood serum and CSF of HE patients is considered the most common laboratory test for diagnosis of HE. EEG abnormalities such as diffuse slowing and atypical tri-phasic brain waves are the most common findings in about ¾ HE patients. Brain CT-Scan is normal in majority of HE patients. Global or local hypo perfusion may be seen in SPECT scanning of the brain. MRI findings are abnormal in about 40% of HE patients.Patients with sub acute or acute onset of confusion, seizure, myoloclonus, stroke-like episodes and amnesia whose laboratory serum and CSF tests indicate presence of high titers of anti- thyroid antibodies should be considered for having HE. Vascular myelopathies, CJD, HSP, Myelinoclastic disease like PML, SSPE, ADE, MS and DNL are some of the differential diagnosis of HE.Adrenal corticosteroids are the first line treatment for HE. Recurrent or steroid resistant HE cases may be treated by addition of other immunosuppressant drugs such as Azathioprine, Cyclophosphamide, or Methotrexate to the 1st line therapy.Keywords: Hashimoto Diseases; Encephalopathy; Thyroiditis, Autoimmune; Thyroiditis, Autoimmune, Diagnosis; Thyroiditis, Autoimmune, Therapy.

  19. Thromboembolism as an important complication of inflammatory bowel disease.

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    Bollen, Lize; Vande Casteele, Niels; Ballet, Vera; van Assche, Gert; Ferrante, Marc; Vermeire, Séverine; Gils, Ann

    2016-01-01

    Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic events (TE) compared with the healthy population. This study aimed to describe a cohort of IBD patients with a history of TE focusing on recurrence of TE, disease activity and IBD medication at the time of TE and surgery before TE. In a retrospective monocentric cohort study, we included IBD patients in whom an arterial and/or venous TE occurred. Eighty-four IBD patients with a history of TE (63% Crohn's disease, 44% men) and a mean age of 45±15 years were included; 25/84 patients (30%) were identified to have recurrent TE. Seventy out of 84 (83%) developed a venous TE, with a deep vein thrombosis as the major manifestation (28/70, 40%), followed by a pulmonary embolism (16/70, 23%). At the time of TE, 60/84 (71%) patients were diagnosed with active disease. In all, 23% patients were on 5-aminosalicylic acids, 36% on steroids, 18% on azathioprine, 5% on methotrexate, 12% on biologicals and 23% were not receiving specific IBD treatment. Moreover, within a 6-month period preceding the TE, 28/84 (33%) patients underwent surgery, of whom 17% received thromboprophylaxis at hospital discharge. We confirm the association between disease activity and the occurrence of TE. A substantial number of patients had additional risk factors such as recurrence of TE. In all, 36% received steroids at the time of TE and 33% underwent recent surgery, of whom only a minority received thromboprophylaxis at hospital discharge. Further efforts are required to increase thromboprophylaxis in at-risk patients.

  20. Evaluation of protective effect of hydroalcoholic extract of Crocus sativus petals on preventing of gentamicin induced peliosis hepatis and hepatic telangiectasis in rats: short communication

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    Arash Omidi

    2013-02-01

    Full Text Available Peliosis hepatis is a rare liver disease characterized by blood-filled cavities scattered irregularly throughout the liver. Risk factors for peliosis include chronic illness such as AIDS, tuberculosis, cancer also use of some drugs such as anabolic steroids and azathioprine. The aim of the present study was to evaluate the curative properties of crocus sativus petals on induced peliosis hepatis in rats. Thirty two male Wistar rats (weight: 180-220 g were randomly divided into four equal groups: group 1 (healthy group received only IP normal saline, group2 received IP 80mg/kg.bw gentamicin, group3 IP 80mg/kg.bw gentamicin+ 40mg/kg crocus sativus petal extract, and group 4 was given IP 80mg/kg.bw gentamicin+ 40mg/kg crocus sativus petal extract. At the end of the experiment, the rats were anesthetized and their blood samples were collected through cardiac puncture for AST and ALT measurement.Then, the livers of the subjects were excised and fixed in formalin. It was found that AST significantly increased in gentamicin group (P<0.05 compared to the healthy group and groups treated by means of crocus sativus petal extract .Moreover, there was no significant differences between the groups administered the extract and those given gentamicin. Histologically,heterogeneous multiple blood-filled cavities were observed in gentamicin group (2 and the treatment groups (3 and 4. The results of the present study show that doses of hydroalcoholic extract of crocus sativus do not effect on peliosis hepatic and telangiectasis due to gentamicin sulfate in rats