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Sample records for azathioprine

  1. 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...... confirm that breastfeeding during treatment with azathioprine seems safe and should be recommended, considering the extensive beneficial effects Udgivelsesdato: 2008/11/15...

  2. Azathioprine for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Gong, Yanzhang; Christensen, E; Gluud, C

    2007-01-01

    Azathioprine is used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been conflicting.......Azathioprine is used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been conflicting....

  3. Pancytopenia related to azathioprine in rheumatoid arthritis.

    OpenAIRE

    Jeurissen, M E; Boerbooms, A M; van de Putte, L B

    1988-01-01

    Two patients with rheumatoid arthritis developed pancytopenia during treatment with azathioprine 100 mg daily. In one patient this side effect occurred after three weeks, in the other after eight weeks of treatment. Rapid fall of platelets in one patient necessitated platelet transfusion. In the other patient additional treatment with allopurinol was probably responsible for the toxic effect. Haematological side effects of azathioprine are discussed.

  4. Glutathione transferases in the bioactivation of azathioprine.

    Science.gov (United States)

    Modén, Olof; Mannervik, Bengt

    2014-01-01

    The prodrug azathioprine is primarily used for maintaining remission in inflammatory bowel disease, but approximately 30% of the patients suffer adverse side effects. The prodrug is activated by glutathione conjugation and release of 6-mercaptopurine, a reaction most efficiently catalyzed by glutathione transferase (GST) A2-2. Among five genotypes of GST A2-2, the variant A2*E has threefold-fourfold higher catalytic efficiency with azathioprine, suggesting that the expression of A2*E could boost 6-mercaptopurine release and adverse side effects in treated patients. Structure-activity studies of the GST A2-2 variants and homologous alpha class GSTs were made to delineate the determinants of high catalytic efficiency compared to other alpha class GSTs. Engineered chimeras identified GST peptide segments of importance, and replacing the corresponding regions in low-activity GSTs by these short segments produced chimeras with higher azathioprine activity. By contrast, H-site mutagenesis led to decreased azathioprine activity when active-site positions 208 and 213 in these favored segments were mutagenized. Alternative substitutions indicated that hydrophobic residues were favored. A pertinent question is whether variant A2*E represents the highest azathioprine activity achievable within the GST structural framework. This issue was addressed by mutagenesis of H-site residues assumed to interact with the substrate based on molecular modeling. The mutants with notably enhanced activities had small or polar residues in the mutated positions. The most active mutant L107G/L108D/F222H displayed a 70-fold enhanced catalytic efficiency with azathioprine. The determination of its structure by X-ray crystallography showed an expanded H-site, suggesting improved accommodation of the transition state for catalysis.

  5. 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/azathi...oprine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/azathi...oprine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/azathi...oprine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archi...ve/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/azathioprine.Rat.in_vivo.Liver.Repeat.zip ...

  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. Are we giving azathioprine too much time?

    Institute of Scientific and Technical Information of China (English)

    Fernando Gomollón; Santiago García López

    2008-01-01

    Azathioprine is Currently the key drug in the maintenance treatment of inflammatory bowel diseases. However, there are still some practical issues to be resolved: one is how long we must maintain the drug. Given that inflammatory bowel diseases are to date chronic, non-curable conditions, treatment should be indefinite and only the loss of efficacy or the appearance of serious side effects may cause withdrawal. As regards to efficacy and their maintenance over time, evidence supports the continuous usefulness of the drug in the long term: in fact its withdrawal very substantially increases the risk of relapse. About side effects, azathioprine is a relatively well tolerated drug and even indefinite use seems safe. The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug. Recent metanalysis suggests that the risk of lymphoma is real, but the individual risk is rather low, and decision analysis suggests a favorable benefit/risk ratio in the long term. Therefore, in patients with inflammatory bowel diseases in whom azathioprine is effective and well tolerated, the drug should not be stopped. This recommendation concerns the use of azathioprine as a single maintenance drug, and is not necessarily applicable to patients receiving concomitant biological therapy.

  8. Spectrophotometric determination of azathioprine in pharmaceutical formulations.

    Science.gov (United States)

    Lakshmi, C S; Reddy, M N

    1998-12-01

    Four simple and sensitive visible spectrophotometric methods (A-D) have been described for the assay of azathioprine (ATP) either in pure form or in pharmaceutical formulations. Methods A and B are based on the oxidation of ATP with excess N-bromosuccinimide (NBS) or chloramine-T (CAT) and determining the consumed NBS or CAT with a decrease in colour intensity of celestine blue (CB) (method A) or gallocyanine (GC) (method B), respectively. Methods C and D are based on the diazotisation of reduced azathioprine (RATP) with excess nitrous acid and estimating either the consumed nitrous acid (HNO(2)) with cresyl fast violet acetate (CFVA) (method C) or by coupling reaction of the diazonium salt formed with N-1-naphthyl ethylene diamine dihydrochloride (NED) (method D). All of the variables have been optimized and the reactions presented. The concentration measurements are reproducible within a relative standard deviation of 1.0%. Recoveries are 99.2-100.3%. PMID:18967434

  9. [Panzytopenia from combination therapy with azathioprin and allopurinol].

    Science.gov (United States)

    Seidel, W

    2004-10-01

    Azathioprine has been used in rheumatology for more than twenty years. Indications are collagen diseases with multiorgan involvement, where co-medications are frequently necessary. We describe a patient suffering from pancytopenia following a combination therapy of azathioprine and allopurinol because of lupus erythematodes and diabetic nephropathy with hyperuricemia. PMID:15517303

  10. Side effects of azathioprine in patients with Crohn's disease.

    NARCIS (Netherlands)

    Jong, Dirk de; Goullet, M.; Naber, A.H.J.

    2004-01-01

    OBJECTIVE: In clinical trials 0-15% of patients discontinued azathioprine due to side effects. The aim of this study was to assess the rate of side effects leading to discontinuation of azathioprine and to determine predictive factors for discontinuation. DESIGN: A retrospective cohort analysis of c

  11. Pancytopenia due to the interaction of allopurinol with azathioprine or mercaptopurine.

    Science.gov (United States)

    2000-04-01

    (1) Allopurinol increases the haematological toxicity of azathioprine and mercaptopurine, with a risk of pancytopenia. (2) Combination of allopurinol with azathioprine or mercaptopurine should be avoided. PMID:11503788

  12. Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study

    Directory of Open Access Journals (Sweden)

    Kaushal K Verma

    2015-01-01

    Full Text Available Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the efficacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92% patients on WAP and 21 (96% on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically significant and comparable (P = 0.366. Patients on WAP had a higher incidence of adverse effects (P = 0.02. Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

  13. Azathioprine-induced Sweet's syndrome and published work review.

    Science.gov (United States)

    Choonhakarn, Charoen; Chaowattanapanit, Suteeraporn

    2013-04-01

    Hypersensitivity to azathioprine can manifest with a wide clinical spectrum. Azathioprine-induced Sweet's syndrome (SS) is rare and usually overlooked because it can mimic disease exacerbation and sepsis. This study aims to characterize the clinical findings of azathioprine-induced SS. A retrospective analysis of the records of three patients diagnosed with azathioprine-induced SS and a review of the relevant English-language published work was performed. Twelve (71%) of the 17 patients were male, ranging 9-89 years in age (mean, 47.2). The time of onset after starting azathioprine was 5-28 days (mean, 13.3). The most common associated disease was inflammatory bowel disease including ulcerative colitis and Crohn's disease (76%). The clinical features typically consisted of fever and classic rash of SS with pustules and vesicles. The lesions occurred most commonly on the face and trunk. Systemic involvement was rare and no hypotension or shock was reported as seen in azathioprine hypersensitivity syndrome. Thiopurine methyltransferase activity is not predictive of this type of adverse effect. Most patients dramatically responded to systemic corticosteroids. Azathioprine-induced SS may be underdiagnosed because it can be easily misinterpreted as inflammatory bowel disease-associated skin eruption. Patients with inflammatory bowel disease may be at higher risk of this condition. Early recognition and drug withdrawal can decrease morbidity of the patients. PMID:23294021

  14. Histiocytoid Sweet syndrome treated with azathioprine: a case report.

    Science.gov (United States)

    Miller, Jonathan; Lee, Nicole; Sami, Naveed

    2015-01-01

    Histiocytoid Sweet syndrome (HSS) is a rare histologic variation of Sweet syndrome (SS) predominantly exhibiting mononuclear histiocytoid cells instead of neutrophils. We report a 22-year-old woman with HSS, who, after minimal improvement with colchicine and dapsone, had significant improvement of her cutaneous eruption and systemic symptoms following empiric treatment with azathioprine. Since azathioprine has historically been known to cause SS, this case highlights a previously unreported treatment response for the histiocytoid variant. PMID:26436977

  15. Histiocytoid Sweet syndrome treated with azathioprine: a case report

    OpenAIRE

    Miller, Jonathan; Lee, Nicole; Sami, Naveed

    2015-01-01

    Histiocytoid Sweet syndrome (HSS) is a rare histologic variation of Sweet syndrome (SS) predominantly exhibiting mononuclear histiocytoid cells instead of neutrophils. We report a 22-year-old woman with HSS, who, after minimal improvement with colchicine and dapsone, had significant improvement of her cutaneous eruption and systemic symptoms following empiric treatment with azathioprine. Since azathioprine has historically been known to cause SS, this case highlights a previously unreported t...

  16. 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.

  17. Azathioprine with prednisone for polymyositis. A controlled, clinical trial.

    Science.gov (United States)

    Bunch, T W; Worthington, J W; Combs, J J; Ilstrup, D M; Engel, A G

    1980-03-01

    A controlled, prospective, double-blind, therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis. Sixteen patients received 60 mg prednisone per day plus either azathioprine (2 mg/kg of body weight per day) or placebo for a period of 3 months. Creatine phosphokinase (CPK) levels fell to normal slightly sooner in the placebo group, but not significantly so. The azathioprine group did not become significantly stronger (P = 0.58) and did not manifest significantly greater improvement of histopathologic features of muscle (P = 0.80) than the placebo group. Initial CPK elevations were significantly related to the degree of muscle inflammation (P = 0.037), but this was not the case at 3 months (P greater than 0.05). Normalization of the CPK could not be equated with disease control. Type II fiber atrophy, attributed to steroid therapy, was more marked in women than in men (P less than 0.03). PMID:6986827

  18. Treatment of Crohn's disease recurrence after ileoanal anastomosis by azathioprine.

    Science.gov (United States)

    Berrebi, W; Chaussade, S; Bruhl, A L; Pariente, A; Valleur, P; Hautefeuille, P; Couturier, D

    1993-08-01

    Ileoanal anastomosis is a surgical procedure performed in patients with ulcerative colitis. In a small number of patients operated on for ulcerative colitis, Crohn's disease occurs in the reservoir, mimicking pouchitis, and may lead to pouch excision and to a permanent terminal ileostomy. Two patients with recurrent Crohn's disease in the reservoir after ileoanal anastomosis were treated with azathioprine for 18 and 24 months, respectively. Azathioprine induced a complete clinical and endoscopic remission. These two observations suggested that immunosuppressive drugs were a good option for permanent ileostomy in cases of recurrence of Crohn's disease in the reservoir after ileoanal anastomosis. PMID:8344116

  19. Biochemical and morphological study on hepatotoxicity of azathioprine in rat.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1979-02-01

    Full Text Available Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.

  20. 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...

  1. 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 hea...

  2. 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...

  3. Azathioprine Induced Pancreatitis in a Patient with Co-Existing Autoimmune Pancreatitis and Hepatitis

    Directory of Open Access Journals (Sweden)

    Preethi GK Venkatesh

    2011-05-01

    Full Text Available Context Azathioprine induced pancreatitis usually runs a benign self limited course with rapid disappearance of signs and symptoms upon with drawl of the drug. Azathioprine is used in treating relapses in patients with autoimmune pancreatitis and maintenance of remission in autoimmune hepatitis. Acute pancreatitis complicated by symptomatic pseudocysts requiring drainage is not usually associated with drug induced pancreatitis. The risk of azathioprine use in patients with underlying disease of pancreas including autoimmune pancreatitis is unclear. Case report We report here a case of an African American patient with co-existing autoimmune pancreatitis and autoimmune hepatitis who developed azathioprine induced acute pancreatitis complicated by a large symptomatic pseudocyst compressing the duodenum requiring a cystoduodenostomy. Conclusions Future studies to investigate the risk of azathioprine induced pancreatitis in the presence of underlying disease of the pancreas including autoimmune pancreatitis are required to further understand the safety of azathioprine in this sub group of patients.

  4. Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase?

    Science.gov (United States)

    Stocco, Gabriele; Pelin, Marco; Franca, Raffaella; De Iudicibus, Sara; Cuzzoni, Eva; Favretto, Diego; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana

    2014-04-01

    Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease (IBD). In vivo it is active after reaction with reduced glutathione (GSH) and conversion to mercaptopurine. Although this reaction may occur spontaneously, the presence of isoforms M and A of the enzyme glutathione-S-transferase (GST) may increase its speed. Indeed, in pediatric patients with IBD, deletion of GST-M1, which determines reduced enzymatic activity, was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites. In addition to increase the activation of azathioprine to mercaptopurine, GSTs may contribute to azathioprine effects even by modulating GSH consumption, oxidative stress and apoptosis. Therefore, genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.

  5. A study of the utility of azathioprine metabolite testing in myasthenia gravis.

    Science.gov (United States)

    Rae, William; Burke, Georgina; Pinto, Ashwin

    2016-04-15

    Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterised by fatigable voluntary skeletal muscle weakness. The underlying pathogenesis is complex involving adaptive autoimmune responses. Azathioprine remains a first line broad acting immunosuppressant for MG. Due to varied clinical responses to azathioprine we aimed to investigate the relationship between azathioprine metabolites and symptom control. Mild correlations between Quantitative Myasthenia Gravis Score (QMG) vs. 6-thioguanine nucleotides (R=-0.317 p=0.186) and QMG vs. lymphocyte count (R=0.402 p=0.08) were found. Azathioprine metabolite measurement should be considered in MG patients with; pancytopenia, deranged liver function or recurrent infections. PMID:27049566

  6. 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

    %) 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...

  7. 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.

  8. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

    Science.gov (United States)

    Chocair, P; Duley, J; Simmonds, H A; Cameron, J S; Ianhez, L; Arap, S; Sabbaga, E

    1993-07-10

    Early rejection can still complicate renal transplantation even with cyclosporin. We added low-dose allopurinol (25 mg on alternative days) to "triple" immunosuppression with cyclosporin, prednisolone, and azathioprine for twelve recipients of cadaver renal grafts. The controls were fifteen patients on triple therapy alone. Only one rejection episode occurred among the allopurinol-treated patients, whereas eleven controls had rejections (seven with more than one episode). Allopurinol may be toxic when combined with azathioprine, yet the bone marrow tolerated the new regimen well. As expected, reduction of the azathioprine dose was necessary in the treated group. PMID:8100914

  9. 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

    ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with a high cumulative dose [≥ 1000 defined daily doses (DDD)] or long-term use (≥ 5 years) of azathioprine, compared with never use of the drug and adjusted for potential confounders. RESULTS: We identified 89 cases and 873 controls....... The prevalence of ever use of azathioprine was similar among cases (39.3%) and controls (39.4%). We observed a slightly elevated OR for cancer overall associated with long-term use of azathioprine (1.22; 95% CI: 0.62-2.40, P = 0.56). The highest ORs were observed for use of 2000 DDD or more of azathioprine...

  10. A case of interstitial pneumonitis in a patient with ulcerative colitis treated with azathioprine

    Institute of Scientific and Technical Information of China (English)

    Ferenc Nagy; Tamas Molnar; Eva Makula; Ildiko Kiss; Peter Milassin; Eva Zollei; Laszlo Tiszlavicz; Janos Lonovics

    2007-01-01

    The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine,whereas interstitial pneumonia is a rare complication.A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever,cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed,and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection,azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.

  11. Electrochemical, spectroscopic, and theoretical studies on the interaction between azathioprine and DNA.

    Science.gov (United States)

    Jalali, Fahimeh; Rasaee, Gelareh

    2015-11-01

    Possible interaction between immunosuppressive drug, azathioprine, and calf thymus DNA was explored by cyclic voltammetry, spectrophotometry, competitive spectrofluorimetry, circular dichroism spectroscopy (CD), and viscosity measurements. Cyclic voltammetry showed negative shift in the reduction peak of azathioprine in the presence of DNA, and large decrease in peak current, referring to the predominance of electrostatic forces. The binding constant was calculated to be 1.22×10(3)M(-1). Absorption hyperchromism without shift in wavelength was observed when DNA was added to azathioprine solution. Competitive fluorescence experiments were conducted by using Hoechst 33258 and methylene blue as probes for minor groove and intercalation binding modes, respectively. The studies showed that azathioprine could release Hoechst 33258, while negligible effect was detected in the case of methylene blue. Stern-Volmer quenching constant (KSV) and complex formation constant (Kf) were obtained from the fluorescence measurements to be 7.6×10(3)M(-1) and 7.76×10(4)M(-1), respectively, at 298K. Enthalpy and entropy changes during the interaction between azathioprine and DNA were calculated from Van't Hoff plot (ΔH=-20.2kJmol(-1); ΔS=26.11Jmol(-1)K(-1) at 298K) which showed an exothermic spontaneous reaction, and involvement of electrostatic forces in the complex formation with DNA. Moreover, circular dichroism studies revealed that azathioprine induced detectable changes in the negative band of DNA spectrum. Viscosity of DNA solution decreased in the presence of azathioprine, showed a non-intercalative mode of interaction. Finally, molecular docking calculations showed that in the lowest energy level of drug-DNA complex, azathioprine approaches the minor grooves of DNA.

  12. Haemolytic anaemia complicating the concurrent use of allopurinol & azathioprine after kidney transplantation

    OpenAIRE

    Neeraj Dhaun; Catherine Hanna; Maria Squires; Simon Watson

    2013-01-01

    Gout is a common problem in renal transplant recipients but often difficult to treat. Allopurinol can be combined with azathioprine but clinicians should be aware of the need for dose reduction, the potential to measure azathioprine breakdown products and the possible side effects of this combination. Leucopenia is a known side effect but this case report shows that haemolytic anaemia can also occur. [Int J Basic Clin Pharmacol 2013; 2(3.000): 330-332

  13. Haemolytic anaemia complicating the concurrent use of allopurinol & azathioprine after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Neeraj Dhaun

    2013-06-01

    Full Text Available Gout is a common problem in renal transplant recipients but often difficult to treat. Allopurinol can be combined with azathioprine but clinicians should be aware of the need for dose reduction, the potential to measure azathioprine breakdown products and the possible side effects of this combination. Leucopenia is a known side effect but this case report shows that haemolytic anaemia can also occur. [Int J Basic Clin Pharmacol 2013; 2(3.000: 330-332

  14. Azathioprine associated acute respiratory distress syndrome: case report and literature review

    Directory of Open Access Journals (Sweden)

    Scherbak D

    2014-08-01

    Full Text Available A 58-year-old Caucasian man treated with azathioprine to prevent rejection of an orthotopic liver transplant, presented to the Carl Hayden VA Medical Center with rapid respiratory decline and appeared septic. He required urgent intubation, mechanical ventilator support and empiric antibiotics. His clinical picture and imaging studies were consistent with acute respiratory distress syndrome; however, extensive infectious work up failed to reveal an offending organism. Review of his current medications implicated azathioprine and upon discontinuation of this agent, the patient made a rapid recovery. He was subsequently extubated, transferred out of the ICU and soon discharged home in good health. Prescribed for organ transplant rejection and a wide array of autoimmune diseases, azathioprine has been rarely correlated with pneumonitis and rapid respiratory failure. No reported cases were found in which azathioprine was used to treat liver transplant rejection and associated with development of the adult respiratory distress syndrome (ARDS. However, there have been ARDS cases in which azathioprine was used for other purposes. We review all the available cases of azathioprine associated ARDS. The patients in these reports had similar clinical symptoms on presentation as our patient: hypoxia, febrile episodes and rapid development of ARDS with no infectious etiology. Most notable is the rapid resolution of ARDS after discontinuation of azathioprine. Although azathioprine toxicity related respiratory failure is rare, this correlation should still be considered in the differential for immunosuppressed patients presenting with rapid pulmonary decline. Further studies are needed and warranted to better correlate this connection, but it is imperative to recognize that the relationship exists.

  15. Role of Rosemary Leaves Extract as A Protective Agent Against Azathioprine-Induced Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Hala M T El-Mougy*, Gehan A Youssef

    2011-04-01

    Full Text Available Background: Rosemary is widely found along the coasts of the Mediterranean Sea. Its leaves or extract were found to have a high antioxidant and anti-inflammatory activity. It is also used as an antispasmodic, analgesic, anti-rheumatic and expectorant. These actions are mainly due to its content of essential oils. Azathioprine (AZA is an immunosuppressive drug. It is widely used in many diseases. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Aim of the work: This work was done to study the effect of dietary supplement of rosemary leaves as a strategy for amelioration of the side-effects of azathioprine. Material and Methods: Thirty-two adult male albino rats were used in this study. They were equally divided into four groups. Group I: control group, group II: rosemary group, the animals were given a daily oral dose of rosemary leaves extract. Group III: azathioprine group, the animals were given a single dose of AZA intraperitoneally. Group IV: rosemary azathioprine group: the rats were given daily doses of rosemary leaves extract then azathioprine in the last day of the experiment as in the previous regimen. The experiment continued for ten days. Blood samples were taken from all groups and examined for tumour necrosis factor alpha, serum amylase enzyme, C-reactive protein and renal function tests (serum urea and creatinine. Results: Rosemary significantly decreased the levels of tumour necrosis factor alpha, serum amylase enzyme and serum urea and C-reactive protein in rosemary AZA group compared to AZA group . Conclusion: The aqueous rosemary leaves extract has the ability to ameliorate the biochemical pathways of the side-effects of azathioprine, so it is advisable to give it concomitantly to patients treated by azathioprine.

  16. Mycophenolate mofetil versus azathioprine for maintenance treatment of lupus nephritis.

    Science.gov (United States)

    Kaballo, Babikir G; Ahmed, Ahmed Elias; Nur, Musa Mohammed; Khalid, Ismail Osman; Abu-Aisha, Hasan

    2016-01-01

    To compare the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) drugs in the maintenance therapy of lupus nephritis (LN) patients, we studied 81 Sudanese patients with LN (32 in Class III, 34 in Class IV, and 15 in combined Class V + IV of the ISN/RPS 2003 Classification). All patients received induction therapy consisting of monthly intravenous pulse doses of cyclophosphamide (CYC) (500 mg/m 2 of body-surface area) for six months, plus three consecutive pulses of intravenous methylprednisolone 15 mg/kg/day of body weight (maximum 500 mg). Subsequently, 41 (50.6%) patients were randomized into a group that received oral MMF (22 mg/kg/day), and 40 (49.4%) patients randomized to a group that received oral AZA (2 mg/kg/day). All patients initially received oral prednisone (1 mg/kg of body weight daily) for four weeks. The baseline characteristics of the two groups were similar. Total remission rate was 75.3% (80.5% in MMF and 70% in AZA), complete remission rate of 54.3% (56.1% with MMF and 52.5% with AZA), and a partial remission rate of 21% (24.4% with MMF and 17.5% with AZA) over 29 months. During maintenance therapy, six patients died (four in the AZA group and two in the MMF group), and end-stage renal disease (ESRD) developed in five patients (three in the AZA group and two in the MMF group). During the 36-months of the study, both groups had comparable event-free survival rate for the composite end point of death or ESRD and rate of relapse-free survival. Furthermore, both groups had no significant differences in terms of frequency of hospitalization, amenorrhea, infection, nausea, and vomiting. We conclude that our study showed that short-term therapy with intravenous CYC followed by maintenance therapy with oral MMF or AZA had similar efficacy and safety for the treatment of patients with moderate to severe LN. PMID:27424688

  17. Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation.

    Science.gov (United States)

    Cummins, D; Sekar, M; Halil, O; Banner, N

    1996-06-15

    It is widely recommended that, during concurrent therapy with allopurinol, the azathioprine dosage should be decreased by at least two thirds. We retrospectively studied compliance with this guideline in 24 patients who had commenced allopurinol at a median of 33 months (range, 2-145 months) after heart and/or lung transplantation. The median reduction in azathioprine dose at initiation of allopurinol was 73.3% but ranged from 0% to 90% (>67% in 14 patients). Within 3 months, 11 (46%) of the patients became leukopenic (white blood cell count azathioprine by two thirds or greater reduced but did not abolish the risk of myelotoxicity. These data highlight the need for close hematological monitoring of patients treated with this drug combination. Agents other than allopurinol should be considered for treating hyperuricemia after thoracic organ transplantation. PMID:8669118

  18. 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 aut

  19. Comparative study of azathioprine-interferon g dispensing to patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Fotios Drakopanagiotakis

    2009-01-01

    Full Text Available SUMMARY. Introduction: Idiopathic pulmonary fibrosis (IPF is characterized by progressive deterioration of lung function, leading ultimately to death. No pharmacological treatment has been found to stabilize the evolution of the disease, but interferon-g and azathioprine have been used as therapeutic options. Aim: To compare the effectiveness of treatment with interferon-g plus low dose prednisone or azathioprine plus low dose prednisone in patients with IPF. Materials and methods: Patients newly diagnosed with IPF were recruited, 22 in total, of whom 10 received azathioprine plus prednisone and 12 patients received interferon-g plus prednisone for six months. Clinical evaluation, lung function tests, HRCT, bronchoscopy and bronchoalveolar lavage (BAL were performed at baseline and after six months of treatment. Results: All patients were alive after six months of treatment. No statistically significant difference between the two groups was detected regarding clinical deterioration, inflammatory biomarkers such as erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and BAL cell sub-populations. There was a trend, not statistically significant, towards a greater reduction in forced vital capacity and diffusing capacity for carbon monoxide in the interferon-g group. Conclusion: Interferon-g does not offer any therapeutic advantage over azathioprine as regards the clinical course, lung function tests and BAL cell counts of patients with IPF. Pneumon 2009, 22(3:240-253.

  20. A Rare Case of Azathioprine-Induced Sweet's Syndrome in a Patient with Crohn's Disease.

    Science.gov (United States)

    Ben Salem, Chaker; Salem, Chaker B; Larif, Sofiene; Fathallah, Neila; Slim, Raoudha; Aounallah, Amina; Sakhri, Jaballah; Hmouda, Houssem

    2015-01-01

    Sweet's syndrome has been reported in association with inflammatory diseases such as Crohn's disease. It has also been reported in association with several drugs. Here, we report a rare case of Sweet's syndrome induced by azathioprine in a patient with Crohn's disease. PMID:26219289

  1. Alcohol binging causes peliosis hepatis during azathioprine therapy in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Christoph Elsing; Joerg Placke; Thomas Herrmann

    2007-01-01

    Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits this environment. Alcohol binging is an increasingly disturbing factor among young people. We describe a patient with Crohn's disease, treated with azathioprine,who developed peliosis hepatis after three epsiodes of alcohol binging. Liver toxicity was not observed previously during the course of the treatment.Azathioprine-induced peliosis hepatis is thought to be idiosyncratic in humans. From animal studies, however,it is clear that hepatic depletion of glutathione leads to azathioprine toxicity to the sinusoidal endothelial cells. Damage of these cells causes peliosis hepatis.Since alcohol binging leads to hepatic glutathione depletion, we conclude that in our patient the episodes of binging have reduced liver gluathione content and therefore this has increased azathioprine toxicity causing peliosis hepatis. The problem of alcohol binging has not yet been addressed in IBD patients undertaking immunosuppressive therapy. This should be reviewed in future considerations regarding patients advice.

  2. Are we giving azathioprine too late? The case for early immunomodulation in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    María Josefina Etchevers; Montserrat Aceituno; Miquel Sans

    2008-01-01

    Inflammatory bowel disease (IBD) includes two entities, Crohn's disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient's quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn's disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn's disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn's disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn's disease patients (AZTEC study).

  3. Azathioprine versus beta interferons for relapsing-remitting multiple sclerosis: a multicentre randomized non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    Luca Massacesi

    Full Text Available 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 β interferons for

  4. 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

  5. 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 of...... diagnosis, participants were randomly allocated to convert to azathioprine after 3-6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death...

  6. [Bone marrow depression after azathioprine. New discoveries on an old drug].

    Science.gov (United States)

    Löwhagen, G B; Lindstedt, G

    2000-02-01

    Azathioprine, a cytostatic and immunosuppressive drug in use for some 30 years, can give rise to life-threatening neutropenia and thrombocytopenia. This may be caused by unexpectedly high concentrations of cytotoxic metabolites due to abnormally slow inactivation of 6-mercaptopurine (6-MP) by thiopurine S-methyltransferase (TPMT) and/or xanthine oxidase. Low TPMT activity may be due to genetic polymorphism or interaction with drugs such as salicylic acid derivatives, while xanthine oxidase may be inhibited by allopurinol. High TPMT activity, on the other hand, may hamper cytostatic treatment. Safer and more effective treatment with azathioprine and its metabolite 6-MP becomes possible with new laboratory methods for pharmacotherapy monitoring. PMID:10707497

  7. Role of Rosemary Leaves Extract as A Protective Agent Against Azathioprine-Induced Toxicity in Rats

    OpenAIRE

    Hala M T El-Mougy*, Gehan A Youssef

    2011-01-01

    Background: Rosemary is widely found along the coasts of the Mediterranean Sea. Its leaves or extract were found to have a high antioxidant and anti-inflammatory activity. It is also used as an antispasmodic, analgesic, anti-rheumatic and expectorant. These actions are mainly due to its content of essential oils. Azathioprine (AZA) is an immunosuppressive drug. It is widely used in many diseases. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Aim of the wor...

  8. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

    OpenAIRE

    Bradford, Kara; Shih, David Q

    2011-01-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as we...

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

    OpenAIRE

    Abdullah Al Maruf; Luke Wan; O’Brien, Peter J

    2014-01-01

    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 sig...

  10. Sweet syndrome on a patient with autoimmune hepatitis on azathioprine and CMV infection.

    Science.gov (United States)

    Xenophontos, Eleni; Ioannou, Antreas; Constantinides, Thrasos; Papanicolaou, Eleni

    2016-02-01

    Sweet syndrome (SS) is a rare inflammatory process presenting with painful erythematous skin eruptions, accompanied by fever and neutrophilia. It is associated with upper respiratory infection in fertile women (classic form), malignancy, infections, drugs and autoimmune diseases. Its pathogenesis remains to be determined. Nevertheless, cytokines may have a prominent role, due to a rapid response after corticosteroid administration. We describe a 32-year-old female with autoimmune hepatitis on azathioprine and prednisone, presenting with fever and inflammatory skin eruptions. Histologic examination of the skin lesions showed neutrophilic infiltrations of the dermis, confirming the diagnosis of SS. Concurrently, she tested borderline positive for recent CMV infection. PMID:26913201

  11. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease.

    Science.gov (United States)

    Bradford, Kara; Shih, David Q

    2011-10-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP. PMID:22072847

  12. Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids.

    Science.gov (United States)

    Allen, L V; Erickson, M A

    1996-08-15

    The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Acetazolamide 25 mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and flucytosine 10 mg/mL were prepared in 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in polyethylene terephthalate bottles. The sources of the drugs were capsules and tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle initially and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 94% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Acetazolamide 25 mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and flucytosine 10 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids. PMID:8862208

  13. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Kara Bradford; David Q Shih

    2011-01-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor a; 6-TGN administration; desensitization trials; and split dosing of 6-MP.

  14. 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

    Background: The aim of this study was to describe prescription patterns for azathioprine and corticosteroids for pregnant women with inflammatory bowel diseases (IBD) before, during, and after pregnancy and to describe pregnancy outcomes. Methods: A cohort composed of all singleton pregnancies in...

  15. Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency

    DEFF Research Database (Denmark)

    Yenson, P.R.; Forrest, D.; Schmiegelow, K.;

    2008-01-01

    Immunosuppressive thiopurines like azathioprine, 6-mercaptopurine, and thioguanine are commonly used in inflammatory and neoplastic disorders. A subset of these patients are genetically slow metabolizers due to point-mutations in enzyme thiopurine S-methyltransferase (TPMT), and are at a higher r...

  16. 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

  17. A Case of Crohn’s Disease with Improvement after Azathioprine-Induced Pancytopenia

    Directory of Open Access Journals (Sweden)

    Yong Sung Choi

    2011-07-01

    Full Text Available The immunosuppressant azathioprine (AZA is widely used in the treatment of inflammatory bowel disease (IBD for both inducing and maintaining remission. However, the adverse effects of AZA can often necessitate a dose reduction or discontinuation. Bone marrow suppression is one of the most serious complications with AZA treatment. On the other hand, some reports have suggested that neutropenia during AZA therapy reduced the relapse rates of IBD patients, and there have been some cases where eradication of the sensitized leukocytes by leukapheresis or bone marrow transplantation improved the IBD, which may explain the relevant role of neutropenia in controlling disease activity. This report describes the case of a 22-year-old male patient who had Crohn’s colitis and complicated perianal fistulas that required immunosuppression; he achieved endoscopically determined remission and showed accelerated mucosal healing as well as clinical remission following the AZA-induced pancytopenia.

  18. EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis

    OpenAIRE

    Yee, C; Gordon, C.; Dostal, C.; Petera, P; Dadoniene, J; Griffiths, B; Rozman, B; Isenberg, D; Sturfelt, G; NIVED, O.; Turney, J.; Venalis, A; Adu, D.; Smolen, J.; Emery, P.

    2004-01-01

    Objective: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE).

  19. 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.

  20. 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.

  1. Should 6-thioguanine nucleotides be monitored in heart transplant recipients given azathioprine?

    Science.gov (United States)

    Schütz, E; Gummert, J; Mohr, F W; Armstrong, V W; Oellerich, M

    1996-06-01

    The commonly used immunosuppressive regimen after orthotopic heart transplantation consists of cyclosporine (CsA), azathioprine (AZA), and steroids. Although AZA therapy is generally regarded as unproblematic, its use can be associated with severe side effects, particularly myelosuppression. Since AZA is a prodrug, which must first be metabolized to its active metabolites, AZA therapy, in contrast to CsA therapy, cannot be controlled by measuring blood levels of this drug. Because of the myelosuppressive properties of the AZA metabolites, the 6-thioguanine nucleotides (6-TGN), the white blood cell count is usually monitored in patients on AZA therapy, and AZA is discontinued if neutropenia appears. In a group of 20 consecutive heart recipients, 6-TGN concentrations ranged from allopurinol, an inhibitor of xanthine oxidase, the other major detoxifying enzyme for AZA. In this patient AZA therapy could be individually adapted by RBC 6-TGN monitoring. Based on our experience, we suggest that RBC 6-TGN monitoring allows for better individualization of treatment with AZA and may help avoid fatal complications. PMID:8738760

  2. Evaluation of azathioprine-induced cytotoxicity in an in vitro rat hepatocyte system.

    Science.gov (United States)

    Al Maruf, Abdullah; Wan, Luke; O'Brien, Peter J

    2014-01-01

    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. PMID:25101277

  3. Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

    Science.gov (United States)

    McCarthy, Neil E.; Hedin, Charlotte R.; Sanders, Theodore J.; Amon, Protima; Hoti, Inva; Ayada, Ibrahim; Baji, Vidya; Giles, Edward M.; Wildemann, Martha; Bashir, Zora; Whelan, Kevin; Sanderson, Ian; Lindsay, James O.; Stagg, Andrew J.

    2015-01-01

    Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn’s disease patients (CD patients) and healthy controls. Blood from CD patients included an increased percentage of gut-tropic integrin β7–expressing Vδ2 T cells, while “Th1-committed” CD27-expressing Vδ2 T cells were selectively depleted. A corresponding population of CD27+ Vδ2 T cells was present in mucosal biopsies from CD patients and produced elevated levels of TNFα compared with controls. In colonic mucosa from CD patients, Vδ2 T cell production of TNFα was reduced by pharmacological blockade of retinoic acid receptor-α (RARα) signaling, indicating that dietary vitamin metabolites can influence Vδ2 T cell function in inflamed intestine. Vδ2 T cells were ablated in blood and tissue from CD patients receiving azathioprine (AZA) therapy, and posttreatment Vδ2 T cell recovery correlated with time since drug withdrawal and inversely correlated with patient age. These results indicate that human Vδ2 T cells exert proinflammatory effects in CD that are modified by dietary vitamin metabolites and ablated by AZA therapy, which may help resolve intestinal inflammation but could increase malignancy risk by impairing systemic tumor surveillance. PMID:26168223

  4. Azathioprine therapy selectively ablates human Vδ2⁺ T cells in Crohn's disease.

    Science.gov (United States)

    McCarthy, Neil E; Hedin, Charlotte R; Sanders, Theodore J; Amon, Protima; Hoti, Inva; Ayada, Ibrahim; Baji, Vidya; Giles, Edward M; Wildemann, Martha; Bashir, Zora; Whelan, Kevin; Sanderson, Ian; Lindsay, James O; Stagg, Andrew J

    2015-08-01

    Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn's disease patients (CD patients) and healthy controls. Blood from CD patients included an increased percentage of gut-tropic integrin β7-expressing Vδ2 T cells, while "Th1-committed" CD27-expressing Vδ2 T cells were selectively depleted. A corresponding population of CD27+ Vδ2 T cells was present in mucosal biopsies from CD patients and produced elevated levels of TNFα compared with controls. In colonic mucosa from CD patients, Vδ2 T cell production of TNFα was reduced by pharmacological blockade of retinoic acid receptor-α (RARα) signaling, indicating that dietary vitamin metabolites can influence Vδ2 T cell function in inflamed intestine. Vδ2 T cells were ablated in blood and tissue from CD patients receiving azathioprine (AZA) therapy, and posttreatment Vδ2 T cell recovery correlated with time since drug withdrawal and inversely correlated with patient age. These results indicate that human Vδ2 T cells exert proinflammatory effects in CD that are modified by dietary vitamin metabolites and ablated by AZA therapy, which may help resolve intestinal inflammation but could increase malignancy risk by impairing systemic tumor surveillance. PMID:26168223

  5. Alterations in rat pulmonary macrophage function by the immunosuppressive agents cyclosporine, azathioprine, and prednisolone.

    Science.gov (United States)

    Drath, D B; Kahan, B D

    1983-06-01

    Disturbances of the immune response of the lung induced by the action of immunosuppressive agents on the functional abilities of rat pulmonary alveolar macrophages (PAM) were analyzed following in vitro incubation or in vivo administration (for 30 days) of cyclosporinea, (CsA) azathioprine (Az) or prednisolone (Pr). Two major parameters were analyzed: oxygen consumption and superoxide release as indices of the overall state of oxygen metabolism of these cells reflecting the integrity of PAM oxidative mechanisms of microbicidal activity, and chemotaxis, an event clinically important for normal defense to infection. In vitro incubation with cyclosporine at concentrations as low as 10(-9) M caused a 52% inhibition of PAM superoxide release, but Az had no effect at concentrations up to 10(-6) M. Prednisolone caused a 38% inhibition of superoxide release; comparable levels of inhibition with Pr required concentrations at least 10-fold greater than with cyclosporine. Further experiments indicated that cyclosporine induced a 40% inhibition after contact with PAM for only 30 min. In vivo experiments indicated that cyclosporine (5 mg/kg), Az (20 mg/kg), or Pr (2 or 0.5 mg/kg) administered intraperitoneally had no effect on the number of PAM available for host defense, PAM oxygen consumption, or PAM superoxide release. However, PAM from cyclosporine-treated animals demonstrated complete inhibition of active migration or chemotaxis in modified Boyden chambers upon incubation with formylmethionyl-leucyl-phenylalanine (FMLP). The effect was apparently dampened by simultaneous administration of Pr with cyclosporine. These experiments suggest that with the exception of a marked effect on chemotaxis the in vivo effects of physiologic amounts of cyclosporine on PAM function are modest compared with the marked depression after in vitro addition. PMID:6306880

  6. Generalized Pyoderma Gangrenosum Associated with Ulcerative Colitis: Successful Treatment with Infliximab and Azathioprine.

    Science.gov (United States)

    Chatzinasiou, Foteini; Polymeros, Dimitrios; Panagiotou, Maro; Theodoropoulos, Konstadinos; Rigopoulos, Dimitrios

    2016-04-01

    Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, part of the spectrum of neutrophilic and auto-inflammatory dermatoses. Its pathogenesis is unknown, although immune pathways have been implicated. Lesion biopsies show a predominantly neutrophilic infiltrate. The incidence of PG is uncertain, but it is estimated to be 3-10 per million per year, occurring at any age but most commonly between 20 and 50 years with a possible slightly higher incidence in women. Approximately 50% of patients with PG also have another disease associated with PG. The most common is inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis (UC). Local treatment may be sufficient for mild cases, while for severe cases systemic immunosuppressants are the mainstay (1,2). We report the case of a patient with bullous PG and UC successfully treated with infliximab and azathioprine. A 32-year-old male Caucasian patient presented with painful violaceous vesicles and enlarging bullae of various sizes and with acute onset, located on the trunk and bilaterally on both the lower and the upper extremities. Lesions on the trunk were composed of hemorrhagic pustules with a surrounding erythematous overhanging border. Some of the lesions had undergone central necrosis and ulceration (Figure 1, a-d). The patient reported of the lesions had appeared one week ago, simultaneously with the exacerbation of a known inflammatory bowel disease with hemorrhagic mucoid diarrhea and fever of up to 38.5°C. The patient's medical history included UC affecting the whole colon (pancolitis), diagnosed 5 months prior to the onset of the epidermal lesions, for which the patient was receiving treatment with oral prednisolone 10 mg/day and mesalazine granules. Blood tests showed severe anemia, leukocytosis, and increased inflammatory markers (C-reactive protein, erythrocyte sedimentation rate). Antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) andtibodies, antineutrophil

  7. The haemotoxicity of azathioprine in repeat dose studies in the female CD-1 mouse.

    Science.gov (United States)

    Molyneux, Gemma; Gibson, Frances M; Chen, Christabelle M; Marway, Harpal K; McKeag, Sean; Mifsud, Charles V J; Pilling, Andrew M; Whayman, Matthew J; Turton, John A

    2008-04-01

    Azathioprine (AZA) is a cytotoxic immunosuppressive drug used in the prevention of rejection in organ transplants and the treatment of auto-immune diseases. However, AZA is haemotoxic causing significant bone marrow depression. The present studies were to characterize the haemotoxicity of AZA in the female CD-1 mouse. In Experiment 1, a dose-ranging study, with AZA gavaged daily for 10 days, clinical evidence of toxicity was evident at 125 mg/kg and above. Experiment 2 was a dose-response study with AZA gavaged daily for 10 days at 40-120 mg/kg. At day 1 after the final dose, AZA induced a dose-related pancytopaenia, reduced femoral marrow cellularity, increases in serum levels of the cytokine fms-like tyrosine kinase 3 ligand, reduction in granulocyte-monocyte colony-forming units and erythroid colonies, and increased bone marrow apoptosis. Histology demonstrated hepatocyte hypertrophy, thymic atrophy, reduced splenic extramedullary haemopoiesis, and reduced cellularity of sternal bone marrow. In Experiment 3, AZA was dosed for 10 days at 100 mg/kg with autopsies at 1, 3, 9, 22, 29, 43 and 57 days postdosing. At 1, 3 and 9 days, haematological parameters reflected changes in Experiment 2. At 22/29 days, many blood parameters were returning towards normal; at 43/57 days, most parameters compared with controls. However, there was some evidence of a persistent (i.e. residual/late-stage) mild reduction in RBC and erythroid progenitor cell counts at day 43/57. We conclude that the CD-1 mouse provides an acceptable model for the haemotoxicity of AZA in man.

  8. 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.

  9. Rapamycin instead of mycophenolate mofetil or azathioprine in treatment of post-renal transplantation urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    HU Xiao-peng; MA Lin-lin; WANG Yong; YIN Hang; WANG Wei; YANG Xiao-yong; ZHANG Xiao-dong

    2009-01-01

    Background Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin (RPM) in combination with low-dose calcineurin inhibitor (CNI) in treating 15 renal allograft recipients which developed urothelial carcinoma were observed. Methods Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil (MMF) or azathioprine (Aza). The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4-6 ug/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored. Results Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved, with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments. Conclusion Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.

  10. Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A, prednisolone and azathioprine

    DEFF Research Database (Denmark)

    Pedersen, E B; Poulsen, F R; Zimmer, J;

    1995-01-01

    treatment. Eight weeks' postgrafting medication with cyclosporin A, prednisolone and azathioprine had resulted in survival of 14 out of 15 grafts (93%), compared with 11 out of 14 (79%) in the group treated with cyclosporin A alone. Only 2 out of 13 grafts (15%) survived in placebo-treated animals....... Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need...... for extended immunosuppressive and antiinflammatory therapies after intracerebral grafting of histoincompatible tissues....

  11. Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

    Institute of Scientific and Technical Information of China (English)

    Borja Hernández-Breijo; Luis G Guijarro; Jorge Monserrat; Sara Ramírez-Rubio; Eva P Cuevas; Diana Vara; Inés Díaz-Laviada; M Dolores Fernández-Moreno; Irene D Román; Javier P Gisbert

    2011-01-01

    AIM: To evaluate the efficacy and the safety of aza-thioprine (AZA) and buthionine sulfoximine (BSO) by localized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37'C incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the efficacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as amino-transferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mer-captopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-de-pendent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-ter-minal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localized treatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.

  12. The impact of azathioprine and cyclosporine on long-term function in kidney transplantation.

    Science.gov (United States)

    Montagnino, G; Colturi, C; Tarantino, A; Masa, A; Banfi, G; Aroldi, A; Viganó, E; Cesana, B; Ponticelli, C

    1991-04-01

    To assess the impact of cyclosporine on long-term kidney function in transplant patients, we retrospectively analyzed 273 patients on azathioprine and 308 on CsA with graft functioning at 1 year. To balance the length of follow-ups, the observation of patients was cut at 5 years. Actual graft survival rate at 5 years was similar in Aza and CsA (88% vs. 90%). Multivariate analysis in Aza pts showed that proteinuria (P = 0.006) and hypertension at 1 year (P = 0.002) increased the probability of irreversible graft failure by 2.47 and 2.85, respectively. In CsA patients, proteinuria (P = 0.007) and plasma creatinine higher than 2.5 mg/dl (P = 0.006) increased the probability of graft failure by 5.12 and 6.48, respectively. In both Aza and CsA patients with a follow-up of at least 5 years, plasma creatinine levels were significantly worse at 5 years vs. 1 year (P = 0.004). The slopes of plasma creatinine values plotted vs time were not different between the two groups. Chronic graft dysfunction (CGD) was defined as a stable increase of plasma creatinine of at least 50% above stable values at 1 year. The probability of remaining without CGD at 5 years was 75% for CsA and 80% for Aza patients (P = N.S.). Multivariate analysis of factors influencing the development of CGD showed that hypertension (P = 0.003) and proteinuria at 1 year (P = 0.081) increased the probability of developing CGD by 2.19 and 1.76, respectively, in Aza, while in CsA patients proteinuria only (P = 0.063) increased the probability of developing CGD by 2.29. Graft survival at 5 years after development of CGD was 34% in Aza and 53% in CsA-treated patients. These data confirm that in the long-term CsA does not cause a higher prevalence of CGD and show that, in the presence of CGD, CsA has a superior protective effect than Aza.

  13. Significant Differences Between Crohn's Disease and Ulcerative Colitis Regarding the Impact of Body Mass Index and Initial Disease Activity on Responsiveness to Azathioprine: Results from a European Multicenter Study in 1,176 Patients

    NARCIS (Netherlands)

    M.H. Holtmann; F. Krummenauer; C. Claas; K. Kremeyer; D. Lorenz; O. Rainer; I. Vogel; U. Boecker; S. Boehm; C. Buening; R. Duchmann; G. Gerken; H. Herfarth; N. Luegering; W. Kruis; M. Reinshagen; J Schmidt; A. Stallmach; J. Stein; A. Sturm; P.R. Galle; D.W. Hommes; G. D'Haens; P. Rutgeerts; M.F. Neurath

    2010-01-01

    In a survey comprising 1,176 patients with inflammatory bowel disease (IBD) we recently showed that azathioprine (AZA) beyond 4 years is beneficial in ulcerative colitis (UC) patients and in a subset of Crohn's disease (CD) patients. Here, we show for the first time that azathioprine responsiveness

  14. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Arends, Suzanne; Grootscholten, Cecile; Derksen, Ronald H. W. M.; Berger, Stefan P.; de Sevaux, Ruud G. L.; Voskuyl, Alexandre E.; Bijl, Marc; Berden, Jo H. M.

    2012-01-01

    Objectives The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evaluat

  15. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis.

    NARCIS (Netherlands)

    Arends, S.; Grootscholten, C.; Derksen, R.H.W.M.; Berger, S.P.; Sevaux, R.G.L. de; Voskuyl, A.E.; Bijl, M. van der; Berden, J.H.M.

    2012-01-01

    OBJECTIVES: The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evalua

  16. 硫唑嘌呤治疗炎症性肠病诱发淋巴瘤%Risk of lymphoma after treatment of inflammatory bowel disease with azathioprine

    Institute of Scientific and Technical Information of China (English)

    罗凤燕; 白爱平

    2013-01-01

    Inflammatory bowel disease (IBD) is a chronic,non-specific inflammatory disease of the intestine,characterized by excessive activation of the immune system.Immunosuppressive therapy has been widely and effectively used in IBD patients.However,the occurrence of lymphoma after immunosuppressive therapy for IBD,especially azathioprine,has been recently reported.This article reviews the clinical application of azathioprine in IBD,the possible mechanisms responsible for lymphoma induction by azathioprine,and the assessment of benefit and risk of immunosuppressive therapy for IBD.%炎症性肠病(inflammatory bowel disease,IBD)是一类肠道免疫系统过度激活引起的慢性非特异性炎症性疾病,包括溃疡性结肠炎(ulcerative colitis,UC)与克罗恩病(Crohn′s disease,CD).免疫抑制剂在IBD患者中广泛应用,且对于IBD治疗有效,但是这些药物诱发淋巴瘤的发生报道越来越多,尤其以硫唑嘌呤(azathioprine,AZA)为甚.AZA治疗IBD是否使淋巴瘤风险增加引起越来越多的关注.本文主要对于AZA在IBD临床应用、诱发淋巴瘤发生的可能机制、风险评估等进行讲述.

  17. 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

    the whole trial, and three patients discontinued the trial, two during the run-in period of azathioprine treatment and one at the introduction of PE. The primary efficacy variables were the number of gadolinium-enhancing lesions and the occurrence of new enhancing lesions on serial MRI performed every 3...

  18. 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

  19. Nonicteric liver damage with a gamma-glutamyl transpeptidase level of 5,609 units/l in a renal-transplant recipient receiving azathioprine.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1984-12-01

    Full Text Available A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l and alkaline phosphatase (60.5 Bessey-Lowry units, 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.

  20. 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 < 0.0002] in univariate and multivariate analyses. Conclusions: AZA-induced acute 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

  1. Azathioprine inhibits vaccinia virus replication in both BSC-40 and RAG cell lines acting on different stages of virus cycle.

    Science.gov (United States)

    Damaso, Clarissa R A; Oliveira, Marcus F; Massarani, Susana M; Moussatché, Nissin

    2002-08-15

    In the present study we demonstrate that azathioprine (AZA) inhibits vaccinia virus (VV) replication in both BSC-40 and RAG cell lines, acting on different stages of virus cycle. In BSC-40 cells, early protein synthesis was not significantly affected, but late gene expression was severely impaired. In RAG cells all stages of gene expression were completed during synchronous infection in the presence of the drug. The onset of DNA replication was not affected in RAG cells, but a severe inhibition was observed in BSC-40 cells. Electron microscopic analysis of VV-infected RAG cells treated with AZA revealed brick-shaped particles presenting abnormal definition of the internal structure. Purified virions from AZA-treated RAG cells presented several modifications of the protein content, a lesser amount of DNA, and a lower PFU:particle ratio. Our results suggest that in VV-infected RAG cells AZA interfered with virus morphogenesis, whereas in BSC-40 cells the replicative cycle was inhibited at the DNA replication stage.

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

    International Nuclear Information System (INIS)

    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 IEA 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.)

  3. Effects of carbon tetrachloride and azathioprine on diethylnitrosamine and N-2-fluorenylacetamide-induced hyperplastic liver nodule and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sakata,Tatsuro

    1984-12-01

    Full Text Available Effects of carbon tetrachloride (CCl4 and azathioprine (AZP on the evolution of hyperplastic liver nodules and foci and hepatocellular carcinoma (HCC were tested in short- and long-term in vivo experiments. In diethylnitrosamine (DEN-treated rats, which were fed a N-2-fluorenylacetamide (FAA-containing diet and additionally treated with repeated CCl4 injections, gamma-glutamyl transpeptidase (gamma-GTP-positive hyperplastic nodules were markedly developed in the 8th week of the experiment. However, their number and area in liver sections were remarkably small in DEN-treated rats fed a diet containing both FAA and AZP. Increased area of gamma-GTP-positive foci was also observed in the 12th week in DEN-injected rats fed a choline-devoid died alone or treated with repeated doses of CCl4 alone. Hepatocellular carcinoma in DEN-injected rats treated with both FAA and CCl4 was first detected in the 21st week, and the incidence up to the 36th week was very high. However, no hepatocellular carcinoma developed in DEN-injected rats treated with both FAA and AZP. The increased activity of liver aniline hydroxylase observed 12 h after the administration of FAA, AZP or DEN alone was not observed when AZP was administered simultaneously with FAA to DEN-injected rats. The mechanisms of the effects of CCl4 and AZP on hepatocarcinogenesis are discussed with special reference to drug interaction.

  4. Voltammetric studies of Azathioprine on the surface of graphite electrode modified with graphene nanosheets decorated with Ag nanoparticles.

    Science.gov (United States)

    Asadian, Elham; Iraji Zad, Azam; Shahrokhian, Saeed

    2016-01-01

    By using graphene nanosheets decorated with Ag nanoparticles (AgNPs-G) as an effective approach for the surface modification of pyrolytic graphite electrode (PGE), a sensing platform was fabricated for the sensitive voltammetric determination of Azathioprine (Aza). The prepared AgNPs-G nanosheets were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-vis and Raman spectroscopy techniques. The electrochemical behavior of Aza was investigated by means of cyclic voltammetry. Comparing to the bare PGE, a remarkable enhancement was observed in the response characteristics of Aza on the surface of the modified electrode (AgNPs-G/PGE) as well as a noticeable decrease in its reduction overpotential. These results can be attributed to the incredible enlargement in the microscopic surface area of the electrode due to the presence of graphene nanosheets together with strong adsorption of Aza on its surface. The effect of experimental parameters such as accumulation time, the amount of modifier suspension and pH of the supporting electrolyte were also optimized toward obtaining the maximum sensitivity. Under the optimum conditions, the calibration curve studies demonstrated that the peak current increased linearly with Aza concentrations in the range of 7 × 10(-7) to 1 × 10(-4)mol L(-1) with the detection limit of 68 nM. Further experiments revealed that the modified electrode can be successfully applied for the accurate determination of Aza in pharmaceutical preparations.

  5. Determination of 6-thioguanine and 6-methylmercaptopurine metabolites in renal transplantation recipients and patients with glomerulonephritis treated with azathioprine.

    Science.gov (United States)

    Chrzanowska, M; Krzymański, M

    1999-04-01

    The metabolism of azathioprine (AZA) was studied by monitoring the concentrations of red blood cell (RBC) 6-thioguanine nucleotides (6-TGN) and of 6-methylmercaptopurine metabolites (6-mMP) in 27 renal transplantation recipients and in 10 patient subjects with glomerulonephritis (GN). Concentrations of 6-TGNs and 6-mMP metabolites were measured using high-performance liquid chromatography (HPLC). Six patients from the group of renal transplantation recipients were also administered allopurinol. Median values of RBC 6-TGN and of 6-mMP metabolites concentrations in 21 renal transplantation recipients (without allopurinol) were 122 pmol/8x10(8) RBCs (range, allopurinol were significantly higher, despite AZA dose reduction, compared with the group without allopurinol and were equal to 363 and 122 pmol/8x10(8) RBC, p < 0.004, respectively. No significant differences were found between the concentrations of 6-mMP metabolites in either group. In the group of renal transplantation recipients, a significant correlation between white blood cell (WBC) count and 6-TGN concentration was established (r(s) = -0.59, p < 0.005). In the group of GN patients, the median values of 6-TGN and of 6-mMP metabolites concentrations were 108 pmol/8x10(8) RBCs (range, 0-297) and 420 pmol/8x10(8) RBC (range, 0-1440), respectively. There were no significant correlations between either the WBC count and 6-TGN concentrations or between 6-TGN concentrations and 6-mMP metabolites. We expect the results of our study to provide indications for better individualization of AZA therapy. PMID:10217345

  6. Successful Treatment of Long-Term Severe Progressive Interstitial Pneumonia with Low-Dose Corticosteroid and Azathioprine in a Patient with Diffuse Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Takuya Kotani

    2012-01-01

    Full Text Available For progressive interstitial pneumonia (progressive IP that accompanies diffuse systemic sclerosis (diffuse SSc, no treatment guidelines have yet been established, and it is a complication with a poor prognosis. We herein report a case in which combination therapy of a low-dose corticosteroid and low-dose azathioprine was performed for progressive SSc-IP in a 64-year-old female whose respiratory function was severely damaged for a long period of time and for whom improvement was achieved. The beneficial effect has continued for 3 years with no side effects being observed during the course.

  7. 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.

  8. The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

    Science.gov (United States)

    Liu, Hui; Ding, Liang; Zhang, Fangbin; Zhang, Yu; Gao, Xiang; Hu, Pinjin; Bi, Huichang; Huang, Min

    2015-10-01

    Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S-transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA-related ADRs. PMID:26432087

  9. 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

  10. Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos; Zsofia Czegledi; Tamas Szamosi; Janos Banai; Gyula David; Ferenc Zsigmond; Tunde Pandur; Zsuzsanna Erdelyi; Orsolya Gemela; Janos Papp; Laszlo Lakatos

    2009-01-01

    AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/ biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location ( P = 0.001), presence of perianal disease ( P < 0.001), prior steroid use ( P = 0.006), early AZA ( P = 0.005) or AZA/biological therapy ( P = 0.002), or smoking ( P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

  11. 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

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

    NARCIS (Netherlands)

    Goerres, M.S.; Meijer, J.W.; Wahab, P.J.; Kerckhaert, J.A.; Groenen, P.J.T.A.; Krieken, J.H.J.M. 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: Ni

  13. Altered systemic bioavailability and organ distribution of azathioprine in methotrexate-induced intestinal mucositis in rats

    Directory of Open Access Journals (Sweden)

    Sadaf A Karbelkar

    2016-01-01

    Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also.

  14. Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.

    Directory of Open Access Journals (Sweden)

    Jasmin Prüfer

    Full Text Available Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.

  15. What are the effects of adding azathioprine to corticosteroids in polymyositis?

    Directory of Open Access Journals (Sweden)

    Cristina Meneses

    2015-07-01

    Full Text Available El tratamiento de la polimiositis se basa en el uso de corticoides, con adición de azatioprina en casos de difícil manejo o como medida para disminuir la dosis de corticoides, si bien no existe evidencia clara de su beneficio en el control de síntomas. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos 1 revisión sistemática que incluye sólo un estudio controlado aleatorizado pertinente. Realizamos una tabla de resumen de los resultados utilizando el método GRADE. Se concluye que existe incertidumbre sobre si agregar azatioprina mejora o no la fuerza muscular en la polimiositis porque la certeza de la evidencia es muy baja.

  16. L’azathioprine dans les maladies inflammatoires chroniques intestinales : impact de son métabolisme sur l’efficacité et la sécurité thérapeutique

    OpenAIRE

    Dewit, Olivier

    2012-01-01

    Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side effects and inefficacy are a major concern as they lead to withdrawal of the drug. Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyl transferase is the only one routinely measured by pheno- or genotyping. A decreased TPMT activity results in a potential overdosing of TP drugs leadin...

  17. Oseltamivir

    Science.gov (United States)

    ... system such as azathioprine (Imuran); cyclosporine (Neoral, Sandimmune); cancer chemotherapy medications; methotrexate (Rheumatrex); sirolimus (Rapamune); oral steroids such as dexamethasone ( ...

  18. Thiopurines and inhibition of Rac1 in vascular disease

    NARCIS (Netherlands)

    G. Marinković

    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. Disease Modifying Antirheumatic Drugs (DMARDs) (Beyond the Basics)

    Science.gov (United States)

    ... medications include gold salts, azathioprine , and cyclosporine . Methotrexate — Methotrexate was originally used as a chemotherapy treatment for cancer. When used in much lower doses for rheumatoid ...

  20. Esker Ri Nursing Home, Kilnabinnia, Clara, Offaly.

    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.

  1. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.9.2. Haematological complications. Leukopenia.

    Science.gov (United States)

    2002-01-01

    GUIDELINE: Because leukopenia is relatively common after kidney transplantation, regular screening and careful evaluation of its causes are recommended. Azathioprine and mycophenolate mofetil may lead to leukopenia. The combination of allopurinol and azathioprine should be avoided. Leukopenia is often associated with viral infections. PMID:12091648

  2. Use of thiopurines in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen;

    2013-01-01

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine...

  3. Efficacy of early treatment with infliximab in pediatric Crohn’s disease

    Institute of Scientific and Technical Information of China (English)

    Jong; Seung; Lee; Jee; Hyun; Lee; Ji; Hyuk; Lee; Hye; Jin; Lee; Mi; Jin; Kim; Hae; Jeong; Lee; Yon; Ho; Choe

    2010-01-01

    AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and mainte...

  4. 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...... in the penicillamine and azathioprine groups. The scintimetric method reliably reflected local synovitis activity and its changes but, like grip strength and PIP circumference, was not a representative measure of the overall activity of the disease....

  5. Ulcerative colitis and Sweet’s syndrome: A case report and review of the literature

    OpenAIRE

    Ali, Massud; Duerksen, Donald R

    2008-01-01

    A 47-year-old man with a history of ulcerative colitis on prednisone and azathioprine was admitted to the hospital with a four-day history of fever, skin rash, arthralgias and leukocytosis. A skin biopsy demonstrated neutrophilic infiltration of the dermis that was consistent with Sweet’s syndrome. He improved after several days with an increase in his prednisone and azathioprine. Sweet’s syndrome is a rare cutaneous manifestation of inflammatory bowel disease, with approximately 40 cases rep...

  6. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing.

    Science.gov (United States)

    Teml, Alexander; Schaeffeler, Elke; Herrlinger, Klaus R; Klotz, Ulrich; Schwab, Matthias

    2007-01-01

    This review summarises clinical pharmacological aspects of thiopurines in the treatment of chronic inflammatory bowel disease (IBD). Current knowledge of pharmacogenetically guided dosing is discussed for individualisation of thiopurine therapy, particularly to avoid severe adverse effects. Both azathioprine and mercaptopurine are pro-drugs that undergo extensive metabolism. The catabolic enzyme thiopurine S-methyltransferase (TPMT) is polymorphically expressed, and currently 23 genetic variants have been described. On the basis of an excellent phenotype-genotype correlation for TPMT, genotyping has become a safe and reliable tool for determination of a patient's individual phenotype. Thiopurine-related adverse drug reactions are frequent, ranging from 5% up to 40%, in both a dose-dependent and -independent manner. IBD patients with low TPMT activity are at high risk of developing severe haematotoxicity if pharmacogenetically guided dosing is not performed. Based on several cost-benefit analyses, assessment of TPMT activity is recommended prior to thiopurine therapy in patients with IBD. The underlying mechanisms of azathioprine/mercaptopurine-related hepatotoxicity, pancreatitis and azathioprine intolerance are still unknown. Although the therapeutic response appears to be related to 6-thioguanine nucleotide (6-TGN) concentrations above a threshold of 230-260 pmol per 8 x 10(8) red blood cells, at present therapeutic drug monitoring of 6-TGN can be recommended only to estimate patients' compliance.Drug-drug interactions between azathioprine/mercaptopurine and aminosalicylates, diuretics, NSAIDs, warfarin and infliximab are discussed. The concomitant use of allopurinol without dosage adjustment of azathioprine/mercaptopurine leads to clinically relevant severe haematotoxicity due to elevated thiopurine levels. Several studies indicate that thiopurine therapy in IBD during pregnancy is safe. Thus, azathioprine/mercaptopurine should not be withdrawn in strictly

  7. Use of thiopurines in inflammatory bowel disease.

    Science.gov (United States)

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen; Rogler, Gerhard

    2013-02-21

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine and thioguanine. We will briefly summarize dose recommendations, indications for thiopurine therapy and side effects which are relevant in clinical practice. We discuss some currently debated topics, including the combination of azathioprine and allopurinol, switching of thiopurine therapy in case of side effects, the use of azathioprine in pregnancy, the infection risk using thiopurines and the evidence when to stop thiopurines. Excellent reviews have been published on the thiopurine metabolic pathway which will not be discussed here in detail. PMID:23467510

  8. 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....

  9. 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 transplanta......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...

  10. 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.

    2013-01-01

    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 Rit

  11. 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 ...

  12. Endoscopic case: Crohn’s disease with pyloric stenosis

    OpenAIRE

    Pereira, F

    2012-01-01

    ABSTRACT We present a case of pyloric stenosis that occurred in a patient with ileocolic Crohn’s disease without significant gastric inflammation, and treated with azathioprine and messalamine. Balloon dilatation, steroid therapy, omeprazol and polymeric enteral nutrition were successful to resolve the stenosis. Later the patient was put on infliximab with good clinical response.

  13. Combination therapy of the plaque form of Weber–Christian idiopathic panniculitis

    OpenAIRE

    O. N. Egorova; B S Belov; S G Radenska-Lopovok; Ye. G. Sazhina

    2014-01-01

    Panniculitides are a group of heterogenic inflammatory diseases that involve the subcutaneous fat. Treatment for panniculitides, idiopathic ones in particular, has not been conclusively developed and is generally performed empirically. The paper describes a case successfully treated with glucocorticosteroids in combination with azathioprine for the plaque form of Weber–Christian panniculitis.

  14. 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,

  15. 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

  16. Combination therapy of the plaque form of Weber–Christian idiopathic panniculitis

    Directory of Open Access Journals (Sweden)

    O. N. Egorova

    2012-01-01

    Full Text Available Panniculitides are a group of heterogenic inflammatory diseases that involve the subcutaneous fat. Treatment for panniculitides, idiopathic ones in particular, has not been conclusively developed and is generally performed empirically. The paper describes a case successfully treated with glucocorticosteroids in combination with azathioprine for the plaque form of Weber–Christian panniculitis.

  17. Combination therapy of the plaque form of Weber–Christian idiopathic panniculitis

    Directory of Open Access Journals (Sweden)

    O. N. Egorova

    2014-07-01

    Full Text Available Panniculitides are a group of heterogenic inflammatory diseases that involve the subcutaneous fat. Treatment for panniculitides, idiopathic ones in particular, has not been conclusively developed and is generally performed empirically. The paper describes a case successfully treated with glucocorticosteroids in combination with azathioprine for the plaque form of Weber–Christian panniculitis.

  18. 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”?

  19. Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

    2012-01-01

    We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activatio...

  20. Two Brothers with Skewed Thiopurine Metabolism in Ulcerative Colitis Treated Successfully with Allopurinol and Mercaptopurine Dose Reduction

    OpenAIRE

    Hoentjen, Frank; Hanauer, Stephen B.; de Boer, Nanne K; Rubin, David T.

    2011-01-01

    Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism....

  1. Drug hypersensitivity syndrome

    OpenAIRE

    Rashmi Kumari; Dependra K Timshina; Devinder Mohan Thappa

    2011-01-01

    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 abnormalit...

  2. Epstein-Barr virus-positive post-transplant lymphoproliferative disorder of the central nervous system, after renal transplantation with a discrepancy in viral load between peripheral blood and cerebrospinal fluid

    NARCIS (Netherlands)

    Boersma, Marijke Nynke; van der Zanden, Adri; Laverman, Gozewijn Dirk; Sanders, Jan Stephan; de Vries, Peter Alexander Marcel

    2012-01-01

    A 43-year-old female developed an EpsteinBarr virus (EBV)-positive post-transplant lymphoproliferative disorder (PTLD) in the central nervous system (CNS), 14 years after renal transplantation. One year prior to presentation, the patients treatment regimen was altered from cyclosporine, azathioprine

  3. Pharmacokinetic optimization of immunosuppressive therapy in thoracic transplantation: part I.

    OpenAIRE

    Monchaud, Caroline; Marquet, Pierre

    2009-01-01

    International audience Although immunosuppressive treatments and therapeutic drug monitoring (TDM) have significantly contributed to the increased success of thoracic transplantation, there is currently no consensus on the best immunosuppressive strategies. Maintenance therapy typically consists of a triple-drug regimen including corticosteroids, a calcineurin inhibitor (ciclosporin or tacrolimus) and either a purine synthesis antagonist (mycophenolate mofetil or azathioprine) or a mammali...

  4. Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays

    OpenAIRE

    Kamal, Mohamed A.; Jusko, William J.

    2004-01-01

    Systemic lupus erythematosus is an autoimmune disease primarily affecting women. Currently, systemic lupus erythematosus therapy is suboptimal due to adverse effects of immunosuppressants, particularly corticosteroids. This study determines the single effects of prednisolone, dehydroepiandrosterone, bromocriptine, tamoxifen, mycophenolic acid, 2-chloro-2′-deoxyadenosine, azathioprine, and chloroquine on lectin-stimulated proliferation of human T lymphocytes, as well as determining whether the...

  5. Liver transplantation

    OpenAIRE

    Rodríguez-Perálvarez, M; De La Mata, M; Burroughs, A K

    2014-01-01

    Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients sh...

  6. Budesonide in previously untreated autoimmune hepatitis

    NARCIS (Netherlands)

    Wiegand, J; Schuler, A; Kanzler, S; Lohse, A; Beuers, U; Kreisel, W; Spengler, U; Koletzko, S; Jansen, PLM; Hochhaus, G; Mollmann, HW; Prols, M; Manns, MP

    2005-01-01

    Background: Autoimmune hepatitis (AIH) is a chronic liver disease that is effectively treated with immunosuppressive therapy. Predniso(lo)ne, often in combination with azathioprine, is the basic therapeutic option to induce remission. However, this regimen can cause numerous side effects. The aim of

  7. 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...

  8. 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 re

  9. Is amyloid A (AA) amyloidosis always secondary?

    OpenAIRE

    Maury, C P; Törnroth, T; Wegelius, O

    1985-01-01

    The case is reported of a patient with systemic AA amyloidosis associated with non-specific mesenteric lymphadenitis and chronic sideropenia. Renal, small bowel, and rectal biopsies showed amyloid deposits containing AA protein, as defined by potassium permanganate sensitivity and by reactivity with AA antiserum. Reversal of the nephrotic syndrome occurred during steroid-azathioprine therapy.

  10. Update on thiopurine pharmacogenetics in inflammatory bowel disease.

    Science.gov (United States)

    Roberts, Rebecca L; Barclay, Murray L

    2015-07-01

    Azathioprine and 6-mercaptopurine remain pivotal therapies for the maintenance of disease remission in patients with Crohn's disease and ulcerative colitis. While thiopurine S-methyltransferase deficiency was the first pharmacogenetic phenomenon to be recognized to influence thiopurine toxicity and reliably predict leukopenia, it does not predict other adverse effects, nor does it explain most cases of thiopurine resistance. In recent years, a number of other genetic polymorphisms have received increasing attention in the literature. In particular, SNPs in NUDT15 and in the class II HLA locus have been shown to predict thiopurine-related leukopenia and pancreatitis. The aim of this review is to provide a concise update of genetic variability which may influence patient response to azathioprine and 6-mercaptopurine.

  11. Enkeltcenteropgorelse af nyretransplanterede patienters nyrefunktion og immunsuppressive behandling

    DEFF Research Database (Denmark)

    Frederiksen, A.M.; Ewers, B.; Gasbjerg, A.;

    2008-01-01

    INTRODUCTION: The number of kidney-transplanted patients is growing. This report describes the age, sex distribution, kidney function, graft age, and immunosuppressive drugs of kidney-transplanted patients followed at the outpatient clinic of the nephrology department at Copenhagen University...... (74%) were treated with triple-drug immunosuppression, in most cases (46%) with the combination prednisolone-ciclosporine-azathioprine. During recent years, azathioprine has been increasingly replaced by mycophenolate mofetil. CONCLUSIONS: The majority of kidney-transplanted patients...... with a functioning graft have sufficient kidney function to keep the patients free of uremic symptoms. Hyperparathyroidism is frequent. The immunosuppressive regimens used for kidney-transplanted patients are currently changing Udgivelsesdato: 2008/5/5...

  12. 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.

  13. Hematologic toxicity of immunosuppressive treatment.

    Science.gov (United States)

    Danesi, R; Del Tacca, M

    2004-04-01

    The administration of immunosuppressive agents may be associated with the occurrence of hematologic toxicity, such as anemia, due to bone marrow suppression or hemolysis, leukopenia, and thrombocytopenia. The administration of azathioprine and mycophenolate mofetil is more frequently associated with bone marrow suppression, while hemolytic-uremic syndrome may occur after administration of cyclosporine, tacrolimus, or muromonab (OKT3) and may be associated with the loss of the allograft. Moreover, microangiopathic hemolytic anemia and thrombocytopenia are rare, but potentially severe, complications of immunosuppressive treatment with tacrolimus and cyclosporine; they are characterized by intravascular hemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. Viral infections (cytomegalovirus), administration of antiviral agents (gancyclovir), inhibitors of angiotensin-converting enzyme and angiotensin II receptor antagonists, antibacterial agents (sulfamethoxazole and trimethoprim), and allopurinol may aggravate bone marrow suppression, particularly when administered with agents that interfere with purine biosynthesis, including azathioprine and mycophenolate mofetil. PMID:15110637

  14. [Drug-drug interactions in antirheumatic treatment].

    Science.gov (United States)

    Krüger, K

    2012-04-01

    Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

  15. Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Amoxicillin/clavulanate is associated with liver injury,mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment,but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

  16. 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.

  17. Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation

    OpenAIRE

    G.A. Spinelli; C.R. Felipe; P.G. Machado; Garcia, R.; D.E. Casarini; S.R. Moreira; Park, S. I.; H. Tedesco-Silva Jr.; J.O. Medina-Pestana

    2006-01-01

    The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttrans...

  18. Pancreatic mass as an initial presentation of severe Wegener's granulomatosis

    OpenAIRE

    Valerieva, Yana; Golemanov, Branimir; Tzolova, Nadezhda; Mitova, Rumiana

    2013-01-01

    Acute pancreatitis or a pancreatic mass is a very rare initial presentation of Wegener's granu-lomatosis. A 62-year-old woman presented with tumor-like pancreatitis and otitis media Abdominal ultrasound and magnetic resonance suggested the presence of pancreatic tumor. Ultrasound-guided fine needle aspiration was negative. Distal pancreatic resection and splenectomy were performed and histopathology proved Wegener's vasculitis of the pancreas and spleen. Azathioprine and steroids were subsequ...

  19. 免疫抑制剂及其临床应用进展

    Institute of Scientific and Technical Information of China (English)

    刘汝臣

    2001-01-01

    @@ 临床应用已久的免疫抑制剂,如环磷酰胺(cyclophosphamide,CTX)、甲氨蝶呤(methotrexate,MTX)、硫唑嘌呤(azathioprine,Aza)等在器官移植抗排斥、自身免疫性疾病及肿瘤的治疗上起了重要作用.

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

    OpenAIRE

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

    2014-01-01

    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...

  1. Use of a xanthine oxidase inhibitor in autoimmune hepatitis.

    Science.gov (United States)

    Al-Shamma, Safa; Eross, Balint; Mclaughlin, Simon

    2013-03-01

    A 62-year-old woman with type 1 autoimmune hepatitis (AIH) failed to sustain remission when steroids were withdrawn from a regimen of steroids and azathioprine (AZA). Thiopurine metabolites revealed elevated 6-MMP (6-methyl mercaptopurine) and low 6-TGN (6-thioguanine nucleotide) consistent with AZA-induced hepatotoxicity. Introducing the xanthine oxidase inhibitor allopurinol led to rapid normalization of alanine aminotransferase (ALT) and discontinuation of steroids. PMID:23238820

  2. Acute thiopurine overdose: analysis of reports to a national poison centre 1995-2013

    OpenAIRE

    Gregoriano, Claudia; Ceschi, Alessandro; Rauber-Lüthy, Christine; Kupferschmidt, Hugo; Banner, Nicholas R.; Krähenbühl, Stephan; Taegtmeyer, Anne B

    2014-01-01

    Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were w...

  3. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS)

    OpenAIRE

    Shaman Gill; Amitabh Sagar; Shankar, S.; Velu Nair

    2013-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, ...

  4. Use of Allopurinol to Optimize Thiopurine Immunomodulator Efficacy in Inflammatory Bowel Disease

    OpenAIRE

    Sparrow, Miles P.

    2008-01-01

    The thiopurine immunomodulators azathioprine and 6-mercaptopurine are integral to the management of inflammatory bowel disease (IBD), particularly as corticosteroid-sparing and maintenance agents; however, up to 50% of patients do not adequately respond to these agents. Advances in pharmacogenomics and an increased understanding of thiopurine metabolism have led to the practice of measuring the thiopurine metabolites 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP) to help achieve opt...

  5. Use of thiopurines in inflammatory bowel disease

    OpenAIRE

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen; Rogler, Gerhard

    2013-01-01

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine and thioguanine. We will briefly summarize dose recommendations, indications for thiopurine therapy and side effects which are relevant in clinical practice. We discuss some currently debated topics, ...

  6. Severe Refractory Immune Thrombocytopenia Successfully Treated with High-Dose Pulse Cyclophosphamide and Eltrombopag

    Directory of Open Access Journals (Sweden)

    Faiz Anwer

    2015-01-01

    Full Text Available Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag.

  7. Immunomodulators and Immunosuppressants for Japanese Patients with Ulcerative Colitis

    OpenAIRE

    Shigeki Bamba; Tomoyuki Tsujikawa; Masaya Sasaki; Yoshihide Fujiyama; Akira Andoh

    2011-01-01

    Ulcerative colitis (UC) is characterized by a long-standing chronic course with remissions and exacerbations. Previously, patients do not respond to 5-aminosalicylic acid compounds and corticosteroids are considered for colectomies, however, in recent years, alternative treatments emerged for steroid-refractory or steroid-dependent UC. In this review article, we focus on immunomodulators (such as azathioprine [AZA] and 6-mercaptopurine [6-MP]) and immunosuppressants (such as cyclosporine A [C...

  8. Liver transplantation: immunosuppression and oncology

    OpenAIRE

    Rodríguez-Perálvarez, Manuel; de la Mata, Manuel; Burroughs, Andrew K.

    2014-01-01

    Purpose of review Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients showed t...

  9. Ulcerative colitis after Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Mohammad Aminianfar

    2014-06-01

    Full Text Available A 21 years old man has been complained of bloody diarrhea, liquid stool containing blood, pus, and fecal matter and crampy abdominal pain from four monthes ago. Ulcerative colitis relies upon the patient's history, clinical symptoms, sigmoidoscopic appearance and histology of colonic biopsy specimens. Treatment of patient started with high dose dexamethasone and prednisolone, asacole, suppository, metronidazole. Patient’s condition not improved and patient admitted in hospital. High dose prednisolone, azathioprine, sulfasalazine and folic acid were given.

  10. Post-transplantation diabetes mellitus

    OpenAIRE

    N Zbiti; K Souly; Z Errami; L Guendouz; L Benamar; F Ezaitouni; N Ouzeddoun; R Bayahia; A Chabraoui; H Rhou

    2012-01-01

    To determine the prevalence of post-kidney transplantation diabetes (PTDM) and to assess its risk factors, we retrospectively studied 92 non-diabetic kidney transplant patients. The immunosuppressive drugs used to prevent rejection included prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antimetabolite (azathioprine or mycofenolate mofetil). Diabetes was defined according to the WHO criteria and the American Diabetes Association. The mean age of our patients was 35.8 ±...

  11. Sweet syndrome associated with interferon

    OpenAIRE

    Rodriguez-Lojo, Romina; Castineiras, Iria; Juarez, Yolanda; Lueiro, Mercedes; Armesto, Ana; Fernandez-Diaz, M. Luisa

    2015-01-01

    Although still very rare, drug-related cases of Sweet’s syndrome have been reported. The more frequent associated medications with drug induced Sweet´s syndrome was: tetracyclines, trimethoprim-sulphamethaxazol, azatioprine, all trans retinoic acid, nitrofurantoin, granulocyte colony-stimulating factor, hydralazine, tripharil, lithium, oral contraceptives, furosemide, celecoxib and azathioprine. We only found one case of drug-induced Sweet´s syndrome secondary to pegylated interferon...

  12. Subcutaneous Histiocytoid Sweet Syndrome Associated with Crohn Disease in an Adolescent

    OpenAIRE

    Rosa María Fernández-Torres; Susana Castro; Ana Moreno; Roberto Álvarez; Eduardo Fonseca

    2014-01-01

    We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C) from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, ...

  13. Are we giving biologics too late? The case for early versus late use

    OpenAIRE

    Ricart, Elena; García-Bosch, Orlando; Ordás, Ingrid; Panés, Julián

    2008-01-01

    Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short-term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their on...

  14. Brain Abscess following Rituximab Infusion in a Patient with Pemphigus Vulgaris

    OpenAIRE

    Al-Harbi, Talal M.; Muammer, Shahad A.; Ellis, Ronald J.

    2015-01-01

    Patient: Female, 52 Final Diagnosis: Brain abscess Symptoms: Fever • headache • weakness, left sided Medication: Prednisolone • Azathioprine • Rituximab Clinical Procedure: Stereotactic brain biopsy and LP Specialty: Neurology Objective: Rare disease Background: Immunocompromised patients are at increased risk for developing meningitis or, rarely, brain abscess with opportunistic organisms like Listeria monocytogenes. Case Report: A 52 year-old Saudi Arabian woman who was diagnosed with pemph...

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

    OpenAIRE

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

    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, naproxen and inhaled fluticasone and salbutamol. INVESTIGATIONS: At presentation, the patient underwent physical examination, chest X-ray and high-resolution CT, blood tests, and bronchoalveolar l...

  16. Inflammatory bowel disease: potential therapeutic strategies

    DEFF Research Database (Denmark)

    Nielsen, O H; Vainer, B; Bregenholt, S;

    1997-01-01

    This review deals with potential and possibly primary therapeutics that, through insight into the inflammatory cascade, result in more rational treatment principles replacing the classical therapy of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). These new...... therapies might be useful for IBD patients, especially since the 'classical therapy' with agents like glucocorticoids, sulfasalazine, mesalazine, azathioprine, 6-mercaptopurine, cyclosporin and methotrexate is often only moderately effective and may have important side-effects. Controlled trials...

  17. Hepatocellular carcinoma occurring in a Crohn’s disease patient

    Institute of Scientific and Technical Information of China (English)

    Mitsuaki; Ishida; Shigeyuki; Naka; Hisanori; Shiomi; Tomoyuki; Tsujikawa; Akira; Andoh; Tamio; Nakahara; Yasuharu; Saito; Yoshi-hide; Fujiyama; Mikiko; Takikita-Suzuki; Fumiyoshi; Kojima; Machiko; Hotta; Tohru; Tani; Yoshimasa; Kurumi; Hidetoshi; Okabe

    2010-01-01

    We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn’s disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the nonneoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was...

  18. Cutaneous reactive histiocytosis in dogs: a retrospective evaluation of 32 cases.

    Science.gov (United States)

    Palmeiro, Brian S; Morris, Daniel O; Goldschmidt, Michael H; Mauldin, Elizabeth A

    2007-10-01

    Thirty-two cases of canine cutaneous histiocytosis were retrospectively evaluated. Median age at onset was 4 years. Lesions included nodules and plaques affecting the head/face, trunk and limbs, and erythema, swelling and depigmentation of the nasal planum/nares. Systemic involvement was not ruled out in all cases. All dogs had complete resolution of dermatological lesions after initial treatment (median 45 days). Initial treatment included prednisone +/- antibiotics (12 of 32 dogs), prednisone and tetracycline/niacinamide (four of 32), prednisone and azathioprine (three of 32), tetracycline/niacinamide +/- vitamin E/essential fatty acids (six of 32), antibiotics +/- antihistamines (three of 32), cyclosporine and ketoconazole (one of 32), topical therapy (two of 32), and no treatment (one of 32). Seventeen dogs received maintenance therapy which consisted of tetracycline/niacinamide +/- vitamin E/essential fatty acids (12 of 17), cyclosporine/ketoconazole (two to three times a week) (two of 17), azathioprine daily (one of 17), prednisone/azathioprine (two times a week) (one of 17), and prednisone daily (one of 17). Median follow up was 25 months. Nine dogs had a recurrence of cutaneous histiocytosis (median days to recurrence 130 days), with seven of nine having more than one recurrence. At study completion, six dogs were deceased (no lesions at the time of death) and 26 of 32 were alive with no lesions. Ten of 26 dogs were on maintenance treatment (eight tetracycline/niacinamide, one azathioprine, one vitamin E). Previous dermatological disease and season had no detectable influence on recurrence. Recurrence was significantly more likely in dogs with nasal planum/nares lesions than dogs without these lesions. Tetracycline/niacinamide was an effective treatment option for dogs in this study population.

  19. Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort.

    Science.gov (United States)

    Coghill, A E; Johnson, L G; Berg, D; Resler, A J; Leca, N; Madeleine, M M

    2016-02-01

    Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus. PMID:26824445

  20. Phagocytic cell function in response to immunosuppressive therapy.

    Science.gov (United States)

    Drath, D B; Kahan, B D

    1984-02-01

    The increased incidence of pulmonary infection in human renal allograft recipients is presumably related to antirejection immunosuppressive therapy. To assess immunosuppressive-related disturbances of the immune responses of the lung, we evaluated the functional abilities of the pulmonary alveolar macrophage (PAM) and polymorphonuclear leukocyte (PMN) of rats in chemotaxis, phagocytosis, and superoxide-release assays following 30 days of intraperitoneal administration of cyclosporine, azathioprine, and/or prednisolone sodium succinate. None of these drugs affected superoxide release by stimulated PAMs or PMNs. Except for a transient inhibition by azathioprine, the drugs had no effect on phagocytosis of Staphylococcus aureus by either cell type. On the other hand, cyclosporine inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)-directed chemotaxis by PAMs, and both FMLP and C5a stimulated chemotaxis by PMNs. Azathioprine had more dramatic effects on PAMs than on PMNs and prednisolone at 2 mg/kg inhibited PAMs. The results indicated that, with the exception of chemotaxis, the immunosuppressive agents largely spare nonspecific elements of host defense. PMID:6320765

  1. June 2012 pulmonary journal club

    Directory of Open Access Journals (Sweden)

    Mathew M

    2012-06-01

    Full Text Available No abstract available. Article truncated at 150 words. Idiopathic Pulmonary Fibrosis (IPF continues to be a devastating disease with no clinically significant treatment options. For years the treatment of IPF centered on a trial of prednisone followed by the addition of either cyclophosphamide or azathioprine as a ‘lets see if this helps’ approach. The 2011 ATS Consensus statement on IPF declared that the use of prednisone as monotherapy was not recommended. The consensus statement also yielded a weak recommendation for N-acetylcysteine (NAC as monotherapy, and a weak recommendation of prednisone, azathioprine and NAC as combination therapy. This study is the first large multicenter, double-blind, placebo controlled trial looking at lung function in groups of patients treated with NAC monotherapy verses combination therapy (prednisone + azathioprine + NAC versus placebo. The study was performed throughout 25 centers from 2009-2011. Inclusion criteria were a diagnosis of IPF, age 35-85, FVC > 50% and DLC0 > 30%. A total of 236 …

  2. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, H.S.; Nielsen, S.L.; Larsen, S.; Lokkegaard, H.

    1987-01-01

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug.

  3. 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.

  4. [Kidney transplant program at the Instituto Nacional de Cardiologia Ignacio Chavez].

    Science.gov (United States)

    Mancilla-Urrea, Eduardo; Aburto-Morales, Salvador; Kasep-Bahena, Jorge; Rodríguez-Castellanos, Francisco

    2011-09-01

    The first renal transplant was done on July 22, 1968 and until December, 2010 a total of 865 procedures have been performed. Immunosuppressive protocols have changing with time: from 1968 to 1984 azathioprine + prednisone plus total radiation in some cases; from 1985 to 1998 cyclosporine + azathioprine + prednisone; in 1998 tacrolimus is used for first time; Mofetil micofenolate was available at 2005 and practically has displaced to azathioprine. As far as possible we use some induction therapy. Primary ESRD etiologies were: unknown (74.9%), glomerulonephritis (9.7%) and diabetic nephropathy (4.2%). Recipient's mean age was 29.9 +/- 11.6 years (12-70) and 35 +/- 9.8 years (18-62) in donors. Analysis group for graft and patient survival included 292 transplants (censured for death with functional graft) with a follow-up of 103 months (CI 95%: 99-108). Survival at 1, 5 and 10 years were: 95, 85 and 60% for graft as well as 100, 94 and 90% for patient. In year 2000 we started to perform renal biopsies at transplant (time zero biopsies), those results have been published and at present are a worldwide reference. In September, 2005 laparoscopic donor nephrectomy is initiated, 180 procedures have been done with excellent results. In year 2006, training in renal transplant acquires the endorsement as a Medicine Posgrade recognized by the UNAM School of Medicine. We have participated in 9 national clinical trials and 6 international multicentric ones. Our renal transplant program offers a good choice for patients with low resources with similar results reported in the literature using current immunosuppressive schemes and surgical procedures. Institutional authorities and humanitarian associations support in addition to participation on investigation studies have been of vital importance.

  5. 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.

  6. 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

  7. Concomitant administration of cyclosporin and ketoconazole in renal transplant recipients.

    Science.gov (United States)

    First, M R; Schroeder, T J; Weiskittel, P; Myre, S A; Alexander, J W; Pesce, A J

    1989-11-18

    18 renal transplant recipients receiving cyclosporin, prednisone, and azathioprine were given ketoconazole, a potent inhibitor of the cytochrome P-450 enzyme system. Within a month ketoconazole-induced blockade of cyclosporin metabolism allowed a significant reduction (451 vs 106 mg/day; 77%) of the mean dose of cyclosporin without altering cyclosporin whole blood trough levels, although maximum blood levels were almost halved. This dose reduction was maintained in patients followed up for up to 13 months. Renal and hepatic function were unchanged after the addition of ketoconazole. This drug interaction has the potential to reduce dramatically expenditure on cyclosporin in transplant recipients. PMID:2572912

  8. Reversible Severe Eosinophilic Endomyocardial Fibrosis During Pregnancy: A Case Report.

    Science.gov (United States)

    Pineton de Chambrun, Marc; Charron, Philippe; Vauthier-Brouzes, Danièle; Cluzel, Philippe; Haroche, Julien; Kahn, Jean-Emmanuel; Amoura, Zahir; Aubart, Fleur Cohen

    2015-08-01

    Idiopathic hypereosinophilic syndrome (HES) is a condition of unknown origin characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. Cardiac involvement is rare and threatening accounting for 33% to 43% of death in HES. Management of pregnant patients with HES is challenging and have rarely been reported, particularly in the setting of heart failure.We here report on the case of a 29-year-old woman with HES who developed severe endomyocardial fibrosis with heart failure during pregnancy. Outcome was favorable under treatment with prednisone and azathioprine.This case illustrates a favorable outcome of endomyocardial fibrosis during pregnancy. PMID:26266372

  9. LC-MS/MS Coupled with Stable Isotope Dilution Method for the Quantification of 6-Thioguanine and S6-Methylthioguanine in Genomic DNA of Human Cancer Cells Treated with 6-Thioguanine

    OpenAIRE

    Wang, Hongxia; Wang, Yinsheng

    2010-01-01

    Thiopurines, including mercaptopurine (MP), 6-thioguanine (SG) and azathioprine, are widely used for the treatment of many human diseases including acute lymphoblastic leukemia (ALL). To exert their cytotoxic effect, these prodrugs need to be metabolically activated to SG nucleotides and incorporated into nucleic acids. SG in DNA can be methylated spontaneously to S6-methylthioguanine (S6mG) in the presence of S-adenosyl-L-methionine. It was proposed that S6mG, owing to its high miscoding pot...

  10. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS

    Directory of Open Access Journals (Sweden)

    Shaman Gill

    2013-01-01

    Full Text Available Drug rash with eosinophilia and systemic symptoms (DRESS syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids.

  11. Erythema multiforme possibly triggered by food substances in a dog.

    Science.gov (United States)

    Itoh, Teruo; Nibe, Kazumi; Kojimoto, Atsuko; Mikawa, Mayumi; Mikawa, Kazuhiro; Uchida, Kazuyuki; Shii, Hiroki

    2006-08-01

    A 5-year-old female border collie presented with erythematous skin lesions at the axillae, groin, mucocutaneous junctions, and pinnae. Biopsy revealed lymphocytic interface dermatitis with hydropic degeneration of basal cells and keratinocyte apoptosis. Based on gross and histological features, diagnosis of erythema multiforme was made. The disease was resolved by treatment with azathioprine, prednisolone, and a hypoallergenic diet. Finally, the skin lesion was controlled without drug therapy but recurred easily every time commercial foods except the hypoallergenic diet were used, suggesting that food substances triggered this outbreak. PMID:16953090

  12. Toxin-Induced Autoimmune Hepatitis Caused by Raw Cashew Nuts

    Science.gov (United States)

    Stueck, Ashley; Bansal, Meena

    2016-01-01

    A 64-year-old man with no past medical history presented with abnormally elevated liver enzymes 1 year after developing a diffuse rash thought to be related to eating large quantities of raw cashew nuts. Liver biopsy was performed, which revealed features concerning for drug- or toxin-induced autoimmune hepatitis. The patient began treatment with azathioprine and prednisone, and liver enzymes normalized. We describe a unique case of a toxin-induced autoimmune hepatitis precipitated not by a drug or dietary supplement but by a food product.

  13. Pancolitis with Ischemic Injury as a Complication of Immunosuppressive Treatment in a Patient with Autoimmune Hepatitis: A Case Report

    Directory of Open Access Journals (Sweden)

    A. Dalbeni

    2012-01-01

    Full Text Available Ischemic colitis is a serious drug-induced adverse event. There are only few cases of immunosuppression-associated ischemic colitis described in the literature, but none with a pancolitis-like manifestation. We report the case of a 72-year-old female patient who developed a pancolitis with ischemic injury on immunosuppressive treatment with steroids and azathioprine for autoimmune hepatitis. The patient presented with massive rectal bleeding. Colonoscopy confirmed the diagnosis of pancolitis. The results of histological examination indicated drug-induced ischemic colitis involving the entire colon. This is the first case of ischemic pancolitis mimicking an inflammatory bowel disease (IBD in a patient with immunosuppressive therapy.

  14. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS).

    Science.gov (United States)

    Gill, Shaman; Sagar, Amitabh; Shankar, S; Nair, Velu

    2013-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids. PMID:24014920

  15. Gout in pediatric renal transplant recipients.

    Science.gov (United States)

    Trück, Johannes; Laube, Guido F; von Vigier, Rodo O; Goetschel, Philippe

    2010-12-01

    Clinical gout has rarely been described after pediatric renal transplantation (RTx), although asymptomatic hyperuricemia is common in these patients. We describe three male pediatric patients who presented with gouty arthritis 7-8.5 years following RTx. Since receiving allopurinol, all patients had been free of gouty symptoms. To prevent severe bone marrow depletion, the dosage of azathioprine, an immunosupressant drug, was reduced by 50% to prevent interaction with allopurinol. Because atypical presentation of gout can occur, a high index of suspicion is needed to allow appropriate diagnosis of this disease in patients with skeletal pain after RTx. PMID:20640905

  16. Thrombotic microangiopathy involving the gallbladder as an unusual manifestation of systemic lupus erythematosus and antiphospholipid syndrome: Case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Beatriz De-Leon-Bojorge; Samuel Zaltzman-Girsevich; Arturo Ortega-Salgado; Adelina Prieto-Patron; Ruth Córdoba-Córdoba; Marco Yamazaki-Nakashimada

    2006-01-01

    Gallbladder disease is no more common in patients with systemic lupus erythematosus (SLE) than in the general population. We describe a 17-year-old patient with SLE, who developed nephritis that was well controlled with medications. Initial treatment consisted of azathioprine, aspirin and prednisone with stable control of her symptoms. Two years later she developed a right quadrant abdominal pain,and an abdominal ultrasound revealed microlithiasic cholecystitis. Open cholecystectomy was performed and the histopathological findings revealed vasculitis with thrombotic microangiopathy in the gallbladder. This case presentation illustrates that calculous or acalculous cholecystitis should be considered as a manifestation of active SLE and APS.

  17. Successful treatment of severe refractory lupus hepatitis with mycophenolate mofetil.

    Science.gov (United States)

    Tagawa, Y; Saito, T; Takada, K; Kawahata, K; Kohsaka, H

    2016-04-01

    Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis.

  18. Retroperitoneal fibrosis treated with methylprednisolon pulse and disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Harreby, M; Bilde, T; Helin, P; Meyhoff, H H; Vinterberg, H; Nielsen, V A

    1994-09-01

    The conventional treatment of patients with ureteric obstruction due to retroperitoneal fibrosis (RF) is surgery in combination with long-term corticosteroids. This report describes 11 cases of RF with ureteric obstruction treated with methyl-prednisolon pulse therapy (MPPT) in combination with azathioprine or penicillamine following initial insertion of ureteral stents. The medial treatment suggested was successful in 7 patients, but only moderately effective in the last 4 patients. This principle of non-operative management of RF has not been previously reported. PMID:7817165

  19. Eosinofil enteritis

    DEFF Research Database (Denmark)

    Gjersøe, P; Rasmussen, S N; Hansen, B F

    2000-01-01

    We present a case of eosinophilic enteritis in a 45 year-old male with clinical and radiological signs of stenotic inflammatory ileal disease. A diagnosis of Crohn's disease was considered. He developed small bowel obstruction and sixty cm of obstructed ileum was resected. Histopathological...... examination revealed the diagnosis of eosinophilic enteritis primarily localized to the tunica muscularis. One year postoperatively he relapsed and small bowel X-ray demonstrated 1 m narrow and irregular ileum. He was treated with mesalamine, azathioprine, and cromoglicate, went into remission and fares well...

  20. Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

    Science.gov (United States)

    Blaes, Franz

    2015-04-01

    Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

  1. Thalidomide induces mucosal healing in postoperative Crohn disease endoscopic recurrence

    Science.gov (United States)

    Hu, Huiqin; Wang, Xinying; Liu, Side

    2016-01-01

    Abstract Background: Thalidomide has been successful use in patients with refractory Crohn disease (CD) in recent years. Methods: We collected the data of a postoperative CD patient who was prescribed thalidomide to induce remission and reviewed the relevant literatures. Results: A 51-year-old female was diagnosed as CD after an urgent terminal intestinal resection and presented endoscopic recurrence despite the prophylactic treatment with azathioprine (AZA). Fortunately, she achieved mucosal healing (MH) at a low dose of thalidomide for 15 months. Conclusion: Thalidomide is effective to induce MH in the postoperative CD endoscopic recurrence. PMID:27603389

  2. Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum.

    Science.gov (United States)

    Wan, Joy; Imadojemu, Sotonye; Werth, Victoria P

    2016-01-01

    The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus. PMID:27265072

  3. Non comparative study on various pulse regimens (DCP, DAP and DMP in pemphigus: Our experience

    Directory of Open Access Journals (Sweden)

    Iffat Hassan

    2014-01-01

    Full Text Available Background: Pemphigus has been treated with Dexamethasone Cyclophosphamide Pulse (DCP Therapy since 1981.Various modifications have been suggested in the original regimen. These include Dexamethasone Azathioprine Pulse (DAP and Dexamethasone Methotrexate Pulse (DMP therapies. Aims: To report our experience on the noncomparative study of various Pulse regimens DCP, DAP AND DMP therapies in patients with Pemphigus. Materials and Methods: The patients were put on three regimens depending upon the situation-Conventional DCP, DAP in the reproductive age group, DMP in patients who showed prolonged Phase I more than 12 months while on DCP. Results: 30 patients were put on DCP therapy. The duration of phase I was on an average six months. Relapse was seen in 3 patients in phase IV. 12 patients on DAP therapy were considered. In Phase III 5 patients relapsed in phase IV four patients relapsed. Five patients were put on the DMP. Disease activity was poorly controlled and in three DMP was discontinued. Conclusion: DCP remains the most effective regimen with quickest onset of remission and continuance of remission. In DAP therapy fixation of dose of azathioprine at 50 mgs daily may be counterproductive. DMP does not fulfil the promise of a viable treatment option in recalcitrant pemphigus and this lacunae needs to be plugged.

  4. Renal flare prediction and prognosis in lupus nephritis Hispanic patients.

    Science.gov (United States)

    Mejía-Vilet, J M; Córdova-Sánchez, B M; Arreola-Guerra, J M; Morales-Buenrostro, L E; Uribe-Uribe, N O; Correa-Rotter, R

    2016-03-01

    We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21-46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39-4.59, p flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77-0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01-0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72-107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease. PMID:26405028

  5. The use of cyclosporine modifies the clinical and histopathological presentation of tuberculosis after renal transplantation

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    BIZ Eloir

    2000-01-01

    Full Text Available Tuberculosis is one of the most frequent opportunistic infections after renal transplantation and occurred in 30 of 1264 patients transplanted between 1976 and 1996 at Hospital São Paulo - UNIFESP and Hospital Dom Silvério, Brazil. The incidence of 2.4% is five times higher than the Brazilian general population. The disease occurred between 50 days to 18 years after the transplant, and had an earlier and worse development in patients receiving azathioprine, prednisone and cyclosporine, with 35% presenting as a disseminated disease, while all patients receiving azathioprine and prednisone had exclusively pulmonary disease. Ninety percent of those patients had fever as the major initial clinical manifestation. Diagnosis was made by biopsy of the lesion (50%, positivity to M. tuberculosis in the sputum (30% and spinal cerebral fluid analysis (7%. Duration of treatment ranged from 6 to 13 months and hepatotoxicity occurred in 3 patients. The patients who died had a significant greater number of rejection episodes and received higher doses of corticosteroid. In conclusion, the administration of cyclosporine changed the clinical and histopathological pattern of tuberculosis occurring after renal transplantation.

  6. Pneumocystis jiroveci pneumonia and pneumomediastinum in an anti-TNFα naive patient with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    James C Lee; Deborah C Bell; Richard M Guinness; Tariq Ahmad

    2009-01-01

    We report the case of a 21-year-old man who was noted to have pneumomediast inum dur ing an admission for an acute flare of ulcerative colitis. At that time, he was on maintenance treatment with azathioprine at a dose of 1.25 mg/kg per day, and had not received supplementary steroids for 9 mo. He had never received anti-tumor necrosis factor (TNF)α therapy. Shortly after apparently effective treatment with intravenous steroids and an increased dose of azathioprine, he developed worsening colitic and new respiratory symptoms, and was diagnosed with Pneumocystis jiroveci ( carinii) pneumonia (PCP). Pneumomediastinum is rare in immunocompetent hosts, but is a recognized complication of PCP in human immunodeficiency virus (HIV) patients, although our patient 's HIV test was negative. Treatment of PCP with co-trimoxazole resulted in resolution of both respiratory and gastrointestinal symptoms, without the need to increase the steroid dose. There is increasing vigilance for opportunistic infections in patients with inflammatory bowel disease following the advent of anti-TNFα therapy. This case emphasizes the importance of considering the possibility of such infections in all patients with inflammatory bowel disease, irrespective of the immunosuppressants they receive, and highlights the potential of steroid-responsive opportunistic infections to mimic worsening colitic symptoms in patients with ulcerative colitis.

  7. [Therapy of myositis].

    Science.gov (United States)

    Keck, A D; Walker, U A

    2013-04-01

    Idiopathic inflammatory myopathy consists of dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). At all stages of myositis, physiotherapy is effective in improving muscle strength, endurance and in maintaining joint motion. In DM and PM the therapy is initiated with glucocorticosteroids. Steroid-sparing agents (azathioprine, methotrexate and cyclosporin A) are added to prevent Cushing's syndrome or an unsatisfactory response. Therapy can also be escalated with intravenous immunoglobulins. Tacrolimus and mycophenolate mofetil (MMF) were effective in small case series. Cyclophosphamide is restricted to patients not responding to previous agents. For treatment intensification immunoglobulins can also be combined with MMF. There is not enough evidence to routinely recommend rituximab. The results with TNF-alpha inhibitors and plasmapheresis were negative or inconsistent. In DM skin involvement responds to sun blockers, antimalarials, topical corticosteroids or calcineurin inhibitors. In NAM statins should be discontinued and treatment with prednisone and immunosuppressants initiated. In IBM a therapeutic trial with prednisone, methotrexate or azathioprine may be warranted, especially in cases in which the serum creatine kinase (CK) is elevated or an inflammatory infiltrate is present in the muscle biopsy.

  8. Current and emerging treatment options in the management of lupus

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    Jordan N

    2016-03-01

    Full Text Available Natasha Jordan,1 David D’Cruz2 1Department of Rheumatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, 2Louise Coote Lupus Unit, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, UK Abstract: 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. Keywords: hydroxychloroquine, mycophenolate mofetil, azathioprine, cyclophosphamide, rituximab, belimumab

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

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    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

  10. [Aortitis: report of three cases].

    Science.gov (United States)

    Wurmann, Pamela; Sabugo, Francisca; Cruz, Julio; Díaz, Gonzalo; Sánchez, Felipe; Pino, Sandra; Pezo, Ninette; Díaz, Juan Carlos; Fernández, Cristina

    2014-07-01

    Aortitis is a nonspecific term that describes an inflammation of the aortic wall caused by inflammatory, infectious, paraneoplastic and idiopathic diseases. The symptoms are variable and nonspecific; therefore a high level of clinical suspicion is required to diagnose it. It is often an incidental finding while looking for other diagnoses and it is confirmed mainly through imaging studies. We report three cases of aortitis: A 29-year-old woman presenting with alopecia, oral and nasal ulcers and positive antinuclear antibodies. A CAT scan showed a segmental thickening of thoracic aorta, with dilated and stenotic areas. She was successfully treated with steroids, hydroxychloroquine, cyclophosphamide and azathioprine. A 41-year-old male presenting with dorsal pain and cough. The CAT scan showed an extra-intimal thickening of the descending aorta and stenosis of the celiac artery. The final diagnosis was a polyangiitis and was treated with steroids, cyclophosphamide and azathioprine. A 28-year-old woman presenting with pain in the left upper abdomen. Imaging studies showed a thickening of the aortic arch and subclavian artery. The final diagnosis was sarcoidosis and the patient was treated with prednisone.

  11. 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.

  12. Thiopurine methyltransferase activity in the erythrocytes of adults and children: and HPLC-linked assay.

    Science.gov (United States)

    Micheli, V; Jacomelli, G; Fioravanti, A; Morozzi, G; Marcolongo, R; Pompucci, G

    1997-03-18

    A non-radioactive method that uses reverse-phase high performance liquid chromatography is described for the determination of thiopurine methyltransferase (E.C. 2.1.1.67) activity in human erythrocytes. The method is based on the direct quantitation of 6-methyl-mercaptopurine produced from 6-mercaptopurine by crude erythrocyte lysates. The method is accurate and reliable and suitable for diagnostic use. Activity values in control adults ranged from 5 to 32 pmol/h/mg haemoglobin. The activity in the erythrocytes of adult males was significantly higher compared to females (21 +/- 5 and 15 +/- 8 pmol/h/mg haemoglobin, respectively). The activity measured in the erythrocytes of children (22 +/- 5 pmol/h/mg haemoglobin) did not show any significant difference compared to adults. Thiopurine methyltransferase activity was measured in a female patient with systemic sclerosis who developed severe bone marrow depression after treatment with azathioprine and allopurinol. Activity (6.3 +/- 0.5 pmol/h/mg haemoglobin) was found in the lowest range of controls thus supporting the hypothesis that it could be responsible for increased azathioprine cytotoxicity. PMID:9086303

  13. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

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    Claudia Gregoriano

    Full Text Available Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5. Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8 times the usual dose in adults. Twelve cases (30% had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.

  14. Cyclosporine-associated leukoencephalopathy in organ transplant recipients: experience of three clinical cases.

    Science.gov (United States)

    Muñoz, R; Espinoza, M; Espinoza, O; Andrade, A; Bravo, E; González, F

    2006-04-01

    Leukoencephalopathy is a structural alteration of cerebral white matter mainly involving damage to myelin. Several reports have linked cyclosporine (CsA) with this alteration. The clinical features vary from qualitative alterations of consciousness to neurological deficits. Magnetic resonance imaging (MRI) of the brain demonstrates the damage to the white matter, which is essential for the differential diagnosis. We describe three clinical cases of leukoencephalopathy. The first case is a 43-year-old man received a cadaveric kidney transplant using immunosuppression with of mycophenolate mofetil, prednisone, and CsA. Four months later he developed meningism and bilateral sixth nerve palsy. The second case is a 50-year-old man with a cadaveric kidney transplant received immunosuppressive treatment with azathioprine and prednisone. As a result of gouty arthritis of the ankle, azathioprine was replaced with CsA to allow addition of allopurinol. Two weeks later he developed confusion and personality changes. The third case is a 16-year-old man received a orthotopic liver transplant. Postoperatively he suffered generalized tonic-clonic seizures. In all patients the CsA levels were toxic and signs of neurological alterations were present on MRI. All patients recovered rapidly after CsA withdrawal. PMID:16647511

  15. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

    Science.gov (United States)

    Gregoriano, Claudia; Ceschi, Alessandro; Rauber-Lüthy, Christine; Kupferschmidt, Hugo; Banner, Nicholas R; Krähenbühl, Stephan; Taegtmeyer, Anne B

    2014-01-01

    Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion. PMID:24489721

  16. 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.

  17. Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    Albert J Czaja; Yusuf Bayraktar

    2009-01-01

    Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected through Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis.Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for longterm azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies, and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.

  18. Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: A population-based cohort study in Australia.

    Science.gov (United States)

    Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

    2016-08-01

    Iatrogenic immunosuppression is a strong risk factor for non-Hodgkin lymphoma (NHL) but the dose-related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population-based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984-2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21-4·01] and late NHL (HR 1·78, 95% CI: 1·12-2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk. PMID:27136044

  19. [Autoimmune hepatitis].

    Science.gov (United States)

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  20. [An infected necrosis of the chin].

    Science.gov (United States)

    Muller, B S; van Goor, H F; Rosenberg, A J W P

    2016-07-01

    A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions. PMID:27430038

  1. Immunotherapy Responsive Autoimmune Subacute Encephalitis: A Report of Two Cases

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    Manoj Mittal

    2010-01-01

    Full Text Available Objective. To describe the clinical characteristics and radiological findings in two patients with subacute encephalitis associated with elevated serum voltage-gated potassium channel antibody (VGKCAb and antithyroperoxidase (TPO antibody. Case Reports. Case 1: 63-year-old woman was admitted for altered mental status and possible seizure activity. MRI brain showed hyperintensity in the bilateral hippocampal areas. She was positive for VGKCAb and anti-TPO antibodies. She was treated with steroids, IVIG, plasma exchange and azathioprine. After 8 months, she had marked improvement in her memory and seizures. Case 2: 61-year-old woman was admitted for video EEG monitoring of unclassified seizure and cognitive function decline. MRI of the brain showed mild hyperintensity in bilateral hippocampal areas and significant atrophy in the frontotemporal lesion. Anti-TPO antibody and VGKCAb were positive. She was treated with steroids, plasma exchange and azathioprine. After 9 months, she had marked improvement in her memory and seizures. Conclusion. Autoimmune subacute encephalitis appears to be an underdiagnosed entity. It is important to screen patients with subacute encephalitis for anti-TPO antibody and VGKCAb, particularly in the presence of seizures. Immunosuppressive therapy appears to be effective in treating this entity.

  2. Improved results in high risk cadaveric kidney transplantation

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    Toledo-Pereyra, L.H.; Baskin, S.; McNichol, L.; Edford, G.; Whitten, J.; Allaben, R.

    1980-01-01

    In general, cadaver kidney transplantation survival remains at 40-50% for the first year after transplantation. To compare the beneficial effect of a new immunosuppressive protocol to standard therapy (azathioprine and prednisone), we have studied 30 high risk first cadaveric renal allograft recipients who were randomly selected before (Group A, n.15) and after (Group B, n.15) 10/79. At 12 mos, actuarial graft survival of Group B is 75% compared to 46% in Group A. Actuarial patient survival for Group B is 94% for one year compared to 60% in Group A. We feel that these improved results are related to basic changes in our immunosuppressive protocol. These changes consist of: 1. Low doses of azathioprine and prednisolone (less than 1 mg/kg) with rapid reduction to very low levels (less than 0.3 mg/kg); 2. ALG administration at 30 mg/kg/day for 14 times; 3. Rapid placement (one month) on alternate day steroid therapy; 4. Elimination of steroids for the treatment of rejection; 5. Use of ALG (20 mg/kg/day for 10 days) for the treatment of rejection; 6. Use of ALG combined with modified lymph node irradiation for third rejection episodes; and 7. Long-term intermittent ALG administration provided that kidney function continues to be normal. The best immunosuppressive protocol is clearly the one associated with less morbidity and improved quality of life after transplantation. Our current protocol (Group B) provides the best results.

  3. The effect of nifedipine on renal function in normotensive cyclosporin-A-treated renal allograft recipients.

    Science.gov (United States)

    McNally, P G; Walls, J; Feehally, J

    1990-01-01

    Intrarenal vasoconstriction is a characteristic feature of CsA nephrotoxicity. The influence of nifedipine, a dihydropyridine calcium channel blocker and potent renal vasodilator, on renal haemodynamics was investigated in 11 cyclosporin A (CsA)- and 9 azathioprine (Aza)-treated normotensive long-term renal allograft recipients. Baseline Cr51-EDTA clearance and effective renal plasma flow (ERPF) were similar in both groups. Nifedipine 20 mg twice daily for 28 days significantly increased Cr51-EDTA clearance (+14.8%) in the CsA group; however, ERPF, renal vascular resistance (RVR), and filtration fraction did not change. Nifedipine did not influence renal haemodynamics in the azathioprine group. The increase in Cr51-EDTA clearance in the CsA group did not correlate with baseline renal function, CsA dose or whole blood levels, donor age, duration of graft, or renal functional reserve capacity. This study suggests that nifedipine confers a beneficial effect on renal haemodynamics in long-term CsA-treated renal allograft recipients and appears to improve renal function by a non-haemodynamic mechanism.

  4. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    excretion can be reduced by diuretics or fluoxetine. When drugs such as antifungal imidazoles, azapropazone, or phenylbutazone are permitted to inhibit the metabolism of sulphonylureas, hypoglycemic effects are enhanced and, if unnoticed, may cause brain damage. Fibrates should not be combined with HMG-CoA reductase inhibitors because of the increased risk of myopathy. Patients taking non-selective monoamine oxidase inhibitors should avoid amine-containing foods and drugs such as matured cheeses, meat, yeast extracts, some wines, unfresh protein, and cold-curing medications. The metabolism of azathioprine is inhibited by allopurinol, and this combination requires a reduced dosage of azathioprine. Mercaptopurine, used in the treatment of leukemia, is also a metabolite of azathioprine. Sources of comprehensive information on drug interactions are 1) the "British National Formulary," appendix 1; 2) Chapter 10 of "The Oxford Textbook of Clinical Pharmacology and Drug Therapy"; and 3) a monograph by Stockley entitled "Drug Interactions." PMID:7903448

  5. 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.

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

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    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.

  7. Infliximab in the treatment of amyloidosis secondary to Crohn's disease.

    Science.gov (United States)

    Cabezuelo, Juan B; Egea, Juan P; Ramos, Fernanda; Torrella, Emilio; Muray, Salomé; Alcázar, Concepción

    2012-05-14

    Secondary amyloidosis (AA) is a severe complication of progressed Crohn’s disease (CD) for which no effective treatment exists. We present the exceptional case of a 33 year-old male with moderate renal failure and proteinuria, who was simultaneously diagnosed with AA amyloid nephropathy and oligosymptomatic CD. He was treated with infliximab at 5mg/kg/8 weeks for 4 years, azathioprine at 1-1.5mg/kg/day (first year) and renin-angiotensin-aldosterone system blockers, with no complications. Treatment caused a decrease in proteinuria, improved renal function, and improved inflammatory parameters over time. Inspired by this case, we performed a review of the medical literature and found that infliximab could be a useful tool in the early treatment of amyloidosis secondary to CD.

  8. Intravenous Immunoglobulin and Mycophenolate Mofetil for Long-Standing Sensory Neuronopathy in Sjögren's Syndrome

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Danieli

    2012-01-01

    Full Text Available Sensory neuronopathy is described in association with the Sjögren's syndrome (SS. We studied a 55-year-old woman with a 4-year history of progressive asymmetric numbness, distal tingling, and burning sensation in upper and lower limbs. In a few months, she developed ataxia with increased hypoanaesthesia. Electrodiagnostic tests revealed undetectable distal and proximal sensory nerve action potential in upper and lower limbs. Cervical spine magnetic resonance showed a signal hyperintensity of posterior columns. Previous treatment with high-dose glucocorticoids and azathioprine was ineffective. A combined treatment with intravenous immunoglobulin and mycophenolate mofetil was followed by a progressive and persistent improvement. This case documented the efficacy and the safety of the coadministration of intravenous immunoglobulin and mycophenolate mofetil in sensory neuronopathy associated with SS refractory to conventional immunosuppressive therapy.

  9. A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs

    Directory of Open Access Journals (Sweden)

    G. Pasero

    2011-09-01

    Full Text Available The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and infl ammation, but without any infl uence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs. This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and lefl unomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive (“therapeutic pyramid” or of more aggressive treatment, through the simultaneous use of two or more DMARDs (“combination therapy”.

  10. Management of granulomatous lymphocytic interstitial lung disease in a patient with common variable immune deficiency.

    Science.gov (United States)

    Pathria, Mohini; Urbine, Daniel; Zumberg, Marc Stuart; Guarderas, Juan

    2016-01-01

    A 61-year-old woman presented with longstanding cough and progressive dyspnoea. She underwent an extensive evaluation and was diagnosed with common variable immunodeficiency (CVID) with granulomatous lymphocytic interstitial lung disease (GLILD). She was initially treated with subcutaneous immunoglobulin therapy, having declined intravenous immunoglobulin (IVIG) therapy. She also declined treatment with oral glucocorticoids. Over several months, she became increasingly symptomatic and developed increased pulmonary infiltrates, pleural effusions, mediastinal adenopathy, splenomegaly, pancytopenia and ascites. An interdisciplinary team composed of an immunologist, pulmonologist and haematologist deliberated over a therapeutic management approach. The patient received a recently reported immunotherapy regimen with azathioprine and rituximab. The therapy led to rapid improvement of her constitutional and respiratory symptoms, with clinical and radiographic improvement in her interstitial lung disease, lymphadenopathy, pleural effusions and ascites. This case report reviews the literature surrounding the diagnosis and management of GLILD. PMID:27335365

  11. Pure red cell aplasia following autoimmune hemolytic anemia: An enigma

    Directory of Open Access Journals (Sweden)

    M Saha

    2013-01-01

    Full Text Available A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA, prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  12. 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.

  13. Inflammatory pseudotumour of the maxilla.

    Science.gov (United States)

    Kichenaradjou, A; Barrett, A W; Norris, P; Rowell, N; Newman, L

    2016-09-01

    Inflammatory pseudotumour (IP), also known as inflammatory myofibroblastic tumour (IMT), is a rare lesion of the maxillofacial skeleton and a diagnosis by exclusion. We describe three cases which affected the maxilla, two women and one man of ages 67, 56 and 70 years at presentation. All showed the typical, rather non-specific histopathological features. IgG4-positive plasma cells varied greatly in prominence, and none of the three lesions expressed ALK-1. Both women responded to steroids and radiotherapy, though one also required azathioprine. Despite maxillectomy, radiotherapy, steroids and cyclophosphamide, the man suffered intracranial spread and succumbed to persistent disease. The cases described here demonstrate the clinicopathological difficulties presented by this entity and its aggressive, unpredictable behaviour. PMID:27052813

  14. Pharmacogenomics and personalized medicine: a review focused on their application in the Chinese population.

    Science.gov (United States)

    Shu, Wen-ying; Li, Jia-li; Wang, Xue-ding; Huang, Min

    2015-05-01

    The field of pharmacogenomics was initiated in the 1950s and began to thrive after the completion of the human genome project 10 years ago. Thus far, more than 100 drug labels and clinical guidelines referring to pharmacogenomic biomarkers have been published, and several key pharmacogenomic markers for either drug safety or efficacy have been identified and subsequently adopted in clinical practice as pre-treatment genetic tests. However, a tremendous variation of genetic backgrounds exists between different ethnic groups. The application of pharmacogenomics in the Chinese population is still a long way off, since the published guidelines issued by the organizations such as US Food and Drug Administration require further confirmation in the Chinese population. This review highlights important pharmacogenomic discoveries in the Chinese population and compares the Chinese population with other nations regarding the pharmacogenomics of five most commonly used drugs, ie, tacrolimus, cyclosporine A, warfarin, cyclophosphamide and azathioprine.

  15. Preemptive Renal Transplantation-The Best Treatment Option for Terminal Chronic Renal Failure.

    Science.gov (United States)

    Arze Aimaretti, L; Arze, S

    2016-03-01

    Renal transplantation is the best therapeutic option for end-stage chronic renal disease. Assuming that it is more advisable if performed early, we aimed to show the clinical, social, and economic advantages in 70% of our patients who were dialyzed only for a short period. For this purpose, we retrospectively collected data over 28 years in 142 kidney transplants performed in patients with sports, and reproduction. Immunosuppression consisted of 3 drugs, including steroids, cyclosporine, and azathioprine or mycophenolate. The cost in the 1st year, including patient and donor evaluation, surgery, immunosuppression, and follow-up, was $13,300 USD versus $22,320 for hemodialysis. We conclude that preemptive renal transplantation with <6 weeks on dialysis is the best therapeutic option for end-stage renal failure, especially in developing countries such as Bolivia, where until last year, full public support for renal replacement therapy was unavailable. PMID:27110013

  16. Dissemination of Strongyloides stercoralis in a patient with systemic lupus erythematosus after initiation of albendazole: a case report

    Directory of Open Access Journals (Sweden)

    Hunter Catherine J

    2008-05-01

    Full Text Available Abstract Introduction Strongyloides stercoralis infection affects hundreds of millions of people worldwide. As immigration rates and international travel increase, so does the number of cases of strongyloidiasis in the United States. Although described both in immigrant and in immunosuppressed populations, hyperinfection and dissemination of S. stercoralis following the initiation of antiparasitic medication is a previously unreported phenomenon. Case presentation Here we describe the case of a 38-year-old immunocompromised woman with systemic lupus erythematosus, who developed disseminated disease following treatment with albendazole (400 mg every 12 hours. Notably the patient was receiving oral prednisone (10 mg once daily, azathioprine (50 mg twice daily, and hydroxychloroquine (400 mg daily at the time of hospitalization. The patient was subsequently treated successfully with ivermectin (200 mcg/kg daily. Conclusion The reader should be aware that dissemination of S. stercoralis can occur even after the initiation of antiparasitic medication.

  17. Use of methotrexate in inflammatory bowel disease in 2014: A User’s Guide

    Institute of Scientific and Technical Information of China (English)

    Arun; Swaminath; Raja; Taunk; Garrett; Lawlor

    2014-01-01

    Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn’s disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.

  18. 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.

  19. Eosinophilic gastroenteritis: a challenge to diagnose and treat.

    Science.gov (United States)

    Phaw, Naw April; Tsai, Her Hsin

    2016-01-01

    The patient presented with bloody diarrhoea, and crampy abdominal pains. She was diagnosed with eosinophilic gastroenteritis (EGE) after the finding of persistently high peripheral eosinophil counts and histology of endoscopic biopsies. She responded to steroids but became dependent on it and her symptoms recurred on steroid tapering. There was little improvement with alternative treatment such as budesonides, azathioprine and montelukast. Surprisingly her symptoms improved significantly after she was treated with clarithromycin for chest infection and she was continued on clarithromycin. Her eosinophil counts fell dramatically and follow-up CT (thorax, abdomen and pelvic) scan showed the mucosal thickening had improved. She became completely free of the symptoms since she was on clarithromycin and her eosinophils counts fell within the normal range during the follow-up. PMID:27613263

  20. Dermatological medication effects on male fertility.

    Science.gov (United States)

    Millsop, Jillian Wong; Heller, Misha M; Eliason, Mark J; Murase, Jenny E

    2013-01-01

    Many drugs have been reported to impair semen parameters, leading to temporary or persistent infertility. Therefore, potential fathers may be concerned about the effect of medications on fertility. We searched the MEDLINE database of articles in English combining key terms including "male infertility," "spermatogenesis," "fertility," "drug effects," and "dermatology." Administration of methotrexate and finasteride has resulted in severe oligospermia and reversible infertility. Ketoconazole has had negative effects on sperm motility and testosterone production. Few individual case reports and a limited number of studies have demonstrated negative effects of tetracyclines, erythromycin, chloroquine, glucocorticoids, spironolactone, and antihistamines on fertility. It is important to counsel male patients when appropriate about the reversible negative effect on fertility when taking methotrexate and finasteride, and the adverse effect of ketoconazole. Patients may be reassured that taking oral retinoids, cyclosporine, azathioprine, and tumor necrosis factor alpha inhibitors should not affect their fertility. PMID:23914891

  1. Biotherapies in large vessel vasculitis.

    Science.gov (United States)

    Ferfar, Y; Mirault, T; Desbois, A C; Comarmond, C; Messas, E; Savey, L; Domont, F; Cacoub, P; Saadoun, D

    2016-06-01

    Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV. PMID:26883459

  2. Is the sinusoidal obstructive syndrome post-liver transplantation a pathologic entity with a multifactorial etiology?

    Directory of Open Access Journals (Sweden)

    Luis Miguel Marín-Gómez

    2015-04-01

    Full Text Available The sinusoidal obstructive syndrome is a complication typically associated with hematopoietic stem cell transplantation. This syndrome, more commonly known as veno-occlusive disease, has also been described after liver transplantation. It can have a life-threatening course. Herein, we describe the hepatic graft loss secondary to the development of a sinusoidal obstructive syndrome after a severe acute cellular rejection and toxic levels of once daily modified released tacrolimus (TAC. We discuss the role of the endotheliitis of acute rejection and toxic metabolites of some immunosuppressants such as azathioprine and TAC. Based on the current scientific evidence, we contemplate the possibility that the etiology of sinusoidal obstruction syndrome post-liver transplantation is multifactorial.

  3. [Crohn's disease--standards of treatment 2004].

    Science.gov (United States)

    Kruis, W

    2005-10-12

    In Crohn's disease therapeutic concepts are according to distinct conditions. Course of the disease, the individual disease pattern and the aim of treatment are of particular significance. Care of patients with Crohn's disease requires interdisciplinary cooperation between gastroenterologists and surgeons. Primary therapy in mild to moderate disease comprises aminosalicylates and budesonide. Treatment of refractory or severe cases are corticosteroids. Immunosuppressive therapy is indicated in all kinds of complicated disease. First line immunosuppressants are Azathioprine and 6-Mercaptopurine while Methotrexate, Infliximab, Mycophenolatmofetil and other compounds represent alternative or rescue medications. Maintenance of remission should not be done on a regular basis but rather regarding the individual patients' situation. Risks have to be carefully balanced with possible benefits. The most important aim of treatment is quality of life.

  4. Crohn S Disease and Acne Fulminans as Associated Disoders (Case Report

    Directory of Open Access Journals (Sweden)

    Pecova K

    2015-09-01

    Full Text Available The authors are presenting a rare case of recurrent acne fulminans (AF in man with Crohn‘s disease (CD. First attak of AF as associated disorder was observed at the age of 21 with positivity rheumatoid factor (28.0 U/ml, Creactive protein (86.7 m/l, ANA (1:160, p-ANCA (1:40 and 82 erythrocyte sedimentation rate/1 hour. The second attak of AF was observed after the 4th infliximab (5mg/kg administration, with azathioprine (100mg/day, with positivity Epstein-Barr (EBV Real Time PCR - 1835 copies/ml. The effect of AF therapy was observed after methylprednisolone (0.5-1.0mg/kg/day with isotretinoin (0.2-1.0mg/kg/day administration, with continual infliximab administration.

  5. An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood

    Institute of Scientific and Technical Information of China (English)

    Yusuf Usta; Figen Gurakan; Zuhal Akcoren; Seza Ozen

    2007-01-01

    We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis (ALM) and systemic lupus erythematosus (SLE). The patient presented with jaundice, hepatosplenomegaly, malAlse, polyarthralgia, arthritis and butterfly rash on the face. Laboratory tests revealed severe liver dysfunction, Coombs positive hemolytic anemia and a positive ANA/ anti-dsDNA test. Renal biopsy showed class IIA kidney disease, while liver biopsy showed chronic hepatitis with severe inflammatory activity. The patient satisfied the international criteria for both SLE and ALM. Clinical symptoms and laboratory findings of SLE improved with high dose treatment with corticosteroids and azathioprine, however, remission of the liver disease could not be achieved. Repeat biopsy of the liver after three years of therapy revealed ongoing chronic hepatitis with high level of inflammatory activity. The present case indicates that children with liver dysfunction and SLE should be investigated for ALM. There is much diagnostic and therapeutic dilemma in patients with ALH-SLE overlap syndrome.

  6. Neuromyelitis optica (Devic's syndrome).

    Science.gov (United States)

    Wingerchuk, Dean M; Weinshenker, Brian G

    2014-01-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that selectively targets the optic nerve and spinal cord, although it may also target certain areas of the brain. The majority of cases are associated with relapses. A specific biomarker, an autoantibody that targets aquaporin-4, is present in the majority of patients and facilitates the diagnosis. Detection of this biomarker in serum has enabled recognition of an expanded spectrum of clinical disorders that previously would not have met diagnostic criteria for NMO. Aquaporin-4 IgG1 autoantibodies are pathogenic and produce lesions of the brain when injected intracerebrally or systemically. The clinical course of NMO is dominated by acute attacks. Progressive worsening of disability, as occurs in prototypic multiple sclerosis, is distinctly unusual. Corticosteroids and plasma exchange are useful for management of acute attacks. Several treatments used to prevent attacks of multiple sclerosis are ineffective in this condition; effective immunotherapies include azathioprine, mycophenolate mofetil and rituximab.

  7. 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

    prescription Database, the Danish National Hospital Discharge Registry, the Danish Medical Birth Registry, and review of selected medical records. After exposure to sulfasalazine during pregnancy our data suggest. No significantly increased overall relative risk of congenital abnormalities and no significantly...... 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...... 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...

  8. Xanthoma disseminatum: A progressive case with multisystem involvement

    Directory of Open Access Journals (Sweden)

    A M Attia

    2014-01-01

    Full Text Available Xanthoma disseminatum (XD is a rare, benign, non-Langerhans cell histiocytic disorder. The pathogenesis is not clear. It manifests with multiple, grouped, red-brown to yellow papules and nodules involving the skin, mucous membranes, and internal organs. We present a case of progressive XD in a 10-year-old male child. The patient presented with progressive, bilateral and symmetrical, reddish-brown, coalescent papules on the neck, around both eyes and all over his trunk and extremities. Skin lesions were accompanied by blurred vision and hoarseness of voice. Examination revealed xanthomatous infiltration of cornea, oral, pharyngeal, and laryngeal mucosae. The patient had diabetes insipidus that was diagnosed 2 years before the appearance of skin lesions. Medical treatment with corticosteroids (20 mg/day and azathioprine (2 mg/kg/day did not stop the disease progression.

  9. Chronic inflammatory demyelinating polyradiculoneuropathy in a boy with systemic lupus erythematosus.

    Science.gov (United States)

    Zoilo, Morel Ayala; Eduardo, Benadón; Enrique, Faugier; del Rocio, Maldonado V M

    2010-05-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy. Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease that can affect the central nervous system in about 40% of patients, with prevalence and incidence unknown in the pediatric population due to lack of multicenter studies. We report the case of a 13-year-old Mexican boy, diagnosed with CIDP at the onset of SLE, beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. The patient had positive ANA, antiDNAdc, antiBeta2glycoprotein, anti-cardiolipin, ANCA-C and X. He received intravenous immunoglobulin, cyclophosphamide, steroids, and azathioprine and showed clinical improvement. It is important to take into account the presence of peripheral neurological disorders in patients with pediatric SLE, considering CIDP as an uncommon presentation, making the diagnosis important for better treatment and evolution.

  10. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies, and questions

    Directory of Open Access Journals (Sweden)

    Jay Desai

    2015-01-01

    Full Text Available Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children′s Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  11. 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...

  12. New and emerging trends in the treatment of atopic dermatitis.

    Science.gov (United States)

    Gelbard, Christina M; Hebert, Adelaide A

    2008-01-01

    Atopic dermatitis is a chronic, inflammatory skin condition that affects 10% to 20% of children and 1% to 3% of adults in the US. Symptoms often result in sleeplessness, psychological stress, poor self-esteem, anxiety, and poor school or work performance. The cost of atopic dermatitis is estimated to be US$0.9 to 3.8 billion every year. Topical steroids are first-line treatment for atopic dermatitis, and recent advances in vehicle technologies have resulted in improved patient tolerability and compliance. Topical calcineurin inhibitors are also safe and effective topical treatments for atopic dermatitis, and provide an additional therapeutic option for patients with this disease. Systemic immunomodulators are used in the treatment of severe refractory disease. Cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and interferon gamma have been used in the management of severe atopic dermatitis. This review highlights the current and emerging trends in the treatment of atopic dermatitis. PMID:19920986

  13. Interaction between atracurium and drugs used in anaesthesia.

    Science.gov (United States)

    Chapple, D J; Clark, J S; Hughes, R

    1983-01-01

    The effects of various drugs used during anaesthesia on the neuromuscular blocking activity of atracurium have been studied in anaesthetized cats. Clinically effective doses of diazepam, morphine, pentazocine, pethidine, ketamine, Althesin, methohexitone, Septrin, lignocaine, propranolol, calcium chloride or azathioprine did not significantly alter the neuromuscular blocking action of atracurium. Recovery from atracurium was not prolonged during an infusion of hexamethonium or sodium nitroprusside, indicating that, despite the severe hypotension, the inactivation of atracurium was unimpaired. Similar to that of other competitive neuromuscular blocking agents, the action of atracurium was enhanced by tubocurarine, halothane, gentamycin, neomycin and polymixin and was antagonized by adrenaline and transiently antagonized by suxamethonium. However, pretreatment with suxamethonium did not affect the subsequent block by atracurium. PMID:6688011

  14. 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

    as part of a routine toxicity test. Overall, the work in ICICIS has shown that the immunotoxic actions of two chemicals were detectable within a 28-day subacute oral toxicity test in the rat, provided that the conventional laboratory procedures were extended to include extra investigations. Both......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....... 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...

  15. Primaer cerebral vaskulitis hos børn

    DEFF Research Database (Denmark)

    Pradsgaard, Dan Østergaard; Stausbøl-Grøn, Brian; Østergaard, John Rosendahl;

    2010-01-01

    , in the absence of other known diseases with these findings. MATERIAL AND METHODS: We performed a retrospective review of children below 15 years submitted with CNS vasculitis to the department between 1999 and 2008. RESULTS: Six (two boys, four girls) of ten children with clinical and vascular imaging findings......INTRODUCTION: Primary cerebral vasculitis in children is a newly recognized, rare inflammatory condition affecting the vessels of the brain. It is characterized by newly acquired neurological deficit(s) with angiographic or histological evidence of central nervous system (CNS) vasculitis...... was successful in most of the patients. In two patients with progressive CNS vasculitis, the treatment was supplemented by intravenous cyclophosphamide and azathioprin, respectively. CONCLUSION: Primary CNS vasculitis is an acutely acquired inflammatory disease with severe neurological deficits and sequelae...

  16. A Case of Autoimmune Hepatitis and Bisphosphonate-Related Osteonecrosis of the Jaw

    Directory of Open Access Journals (Sweden)

    Y.S. de Boer

    2012-05-01

    Full Text Available Autoimmune hepatitis (AIH is a chronic inflammatory liver disease of unknown aetiology usually requiring long-term immunosuppressive therapy. We present the case of an AIH patient who received long-term corticosteroids and azathioprine. As treatment for concomitant osteoporosis she was also treated with potent intravenous bisphosphonate (BP. This treatment was complicated by the development of BP-related osteonecrosis of the jaw (BRONJ. BRONJ is an uncommon complication of BP treatment regimes that occurs at increased frequency in the presence of other risk factors, including chronic inflammatory conditions. Our patient suffered from a severe and complicated clinical course of BRONJ which, despite adequate therapy, resulted in death of the patient. Here we discuss the risk factors for the development and clinical course of BRONJ in AIH and the implications for management of these patients.

  17. Treatment of progressive IgA nephropathy: an update.

    Science.gov (United States)

    Wang, Weiming; Chen, Nan

    2013-01-01

    IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. About 25-30% of IgAN patients will progress to end-stage kidney disease in 20-25 years. Early-onset symptoms that are highly suggestive of progressive IgAN include massive proteinuria, hypertension, renal damage, glomerular sclerosis, crescent formation, and tubulointerstitial fibrosis. Progressive IgAN may progress to renal failure in a short time. Optimized supportive therapy is the fundamental treatment for progressive IgAN patients, and includes renin-angiotensin system blockers, blood pressure control, antiplatelet and anticoagulant drugs, statins, and allopurinol. In progressive IgAN patients whose clinical and pathological manifestations are more severe, active therapy may be considered including glucocorticoid therapy, cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, and other immunosuppressants. However, there are currently controversies on the definition and treatment of progressive IgAN. PMID:23689569

  18. [Life-threatening adverse effects of pharmacologic antihyperuricemic therapy].

    Science.gov (United States)

    Russmann, St; Lauterburg, B

    2004-09-01

    Minor hypersensitivity reactions to allopurinol presenting as skin rash occur in approximately 2% of patients. A more severe, albeit rare, hypersensitivity reaction with fever, eosinophilia, dermatitis, renal failure, vasculitis and hepatic dysfunction carries a mortality of up to 20%. The incidence of this severe reaction can probably be reduced by adjusting the dose of allopurinol in patients with impaired renal function. Azathioprine and mercaptopurine are metabolised by xanthine oxidase, the enzyme that is inhibited by allopurinol. Concomitant administration can result in life-threatening neutropenia unless the dose of allopurinol is reduced by approximately 75%. The uricosuric agent benzbromarone has recently been withdrawn from the market because of several cases of fulminant hepatic failure with subsequent death of the patient or liver transplantation. PMID:15493119

  19. Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study.

    Science.gov (United States)

    Zürcher, R M; Bock, H A; Thiel, G

    1994-01-01

    Patients on cyclosporin A (CsA) often develop hyperuricaemia and gout. In transplant patients the use of uricosuric drugs for treating hyperuricaemia may be preferable to allopurinol because of the known interaction of the latter with azathioprine. We therefore prospectively studied the uricosuric efficacy of 100 mg benzbromarone (Bbr;Desuric) daily in 25 CsA-treated renal transplant patients with stable graft function and hyperuricaemia (> 359 mumol/l for females, > 491 mumol/l for males). Benzbromarone decreased plasma uric acid from 579 + 18 mumol/l to 313 +/- 24 mumol/l (mean +/- SEM; P 25 ml/min. Due to its excellent efficacy and lack of significant side-effects, benzbromarone appears to be preferable to allopurinol in CsA-treated renal transplant recipients with a creatinine clearance over 25 ml/min. PMID:8090336

  20. Colchicine myoneuropathy in a renal transplant patient.

    Science.gov (United States)

    Dupont, Peter; Hunt, Ian; Goldberg, Lawrence; Warrens, Anthony

    2002-07-01

    Colchicine is widely employed for the treatment of gout in renal transplant patients where NSAIDs are contra-indicated and allopurinol prophylaxis is often avoided due to concomitant azathioprine immunosuppression. We report here a case of colchicine-induced myoneuropathy in a renal transplant recipient. Our patient had myalgia, muscle weakness, elevated creatine kinase levels, myopathic changes on electromyography and peripheral neuropathy. Withdrawal of colchicine resulted in recovery within 4 weeks. Renal transplant recipients are likely to be at greater risk of colchicine-induced myoneuropathy due to the unique concurrence of risk factors predisposing to toxicity in such patients. These risk factors include the high incidence of gout in this population, widespread use of colchicine as first-line therapy, impaired renal function and concomitant cyclosporin treatment. The diagnosis should be considered in any renal transplant recipient receiving the drug who develops myopathy. Prompt withdrawal of colchicine therapy should result in rapid clinical and biochemical improvement. PMID:12122515

  1. Case reports: treatment of nevirapine-associated dress syndrome with intravenous immune globulin (IVIG).

    Science.gov (United States)

    Fields, Katherine S; Petersen, Marta J; Chiao, Elizabeth; Tristani-Firouzi, Payam

    2005-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse drug reaction most commonly associated with aromatic antiepileptic agents. It is characterized by the triad of skin eruption, fever, and systemic involvement, with the latter usually manifesting as hepatitis and lymphadenopathy. Mortality is primarily due to hepatic failure and can be as high as 10%. Formerly referred to by names such as Dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome, DRESS syndrome is a more precise term since this reaction pattern can be seen with other agents. DRESS syndrome has also been reported in association with sulfonamides, allopurinol, terbinafine, minocycline, azathioprine, and dapsone as well as with several antiretroviral agents such as abacavir and nevirapine. We describe a patient with HIV who developed nevirapine hypersensitivity syndrome who was successfully treated with intravenous immune globulin (IVIG). PMID:16004028

  2. Pregnancy in renal transplant recipients.

    Science.gov (United States)

    Hou, Susan

    2013-05-01

    Fertility in women with kidney failure is restored by transplantation. It requires careful planning and is only advisable in women with good kidney function, controlled blood pressure, and general good health. Immunosuppressive drugs carry risks for the fetus, but the risks of prednisone, azathioprine, cyclosporine, and tacrolimus are surprisingly low. Mycophenolate is teratogenic. The success rate for pregnancy in kidney transplant recipients is lower than in the general population with 70% to 80% of pregnancies resulting in surviving infants. Prematurity, intrauterine growth restriction, and preeclampsia are all increased. Complications are higher and outcomes are worse for women with serum creatinine levels over 1.3 mg/dL. Ten to 15% of women have a temporary or permanent decline in kidney function, particularly if prepregnancy creatinine is high. Transplant-related infections can be serious for the mother and fetus. A multidisciplinary team should coordinate care. PMID:23928390

  3. [Combination biological therapy for fistular Crohn's disease: clinical demonstration].

    Science.gov (United States)

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Konoplyannikov, A G; Ruchkina, I N; Lischchinskaya, A A

    2014-01-01

    Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD. PMID:24772517

  4. A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Shumei Zheng; Hui Xu; Qin Ouyang; Linyun Xue; Yong Zhang; Dejun Cui

    2013-01-01

    A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission.The colonoscopy revealed multifocal ulcers in the colon.Histology showed active chronic inflammation.Although anti-tuberculosis medication was effective,his symptoms repeated 2 months later.The subsequent colonoscopy revealed more extensive irregular ulcers than before,and he was clinically suspected with intestinal malignant lymphoma.He underwent subtotal colectomy and was histologically suggested Crohn's disease,then 5-aminosalicylic and a combination of prednisone and azathioprine were administered in succession postoperatively,but they achieved minimal relief of symptoms for a period of 7 months.The third colonoscopy showed a large irregular ulcer in the ileocolon stomas,and primary colonic NK/T cell lymphoma was diagnosed through histological and immunophenotypic studies.Malignant lymphoma should be taken into consideration when clinically diagnosed Crohn's disease was refractory to medication or when its clinical course became aggressive.

  5. Diagnosis and treatment of fistulising Crohn's disease

    DEFF Research Database (Denmark)

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

    2011-01-01

    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....../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...... 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...

  6. Update on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Peter R Galle; Stephan Kanzler

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

  7. Food allergen-mediated exacerbations of oral lichen planus.

    Science.gov (United States)

    Chen, H X; Yount, W J; Culton, D A

    2016-10-01

    Erosive oral lichen planus (OLP) is a chronic autoimmune condition of unknown aetiology, characterized by periods of exacerbation and quiescence. Many patients with OLP report triggers of flares that overlap with triggers of other oral diseases, including oral allergy syndrome (OAS), an IgE-mediated food allergy. We report a case that, to our knowledge, is the first reported case of concurrent OLP and OAS diagnoses, which provides insight into the triggers of OLP and the role of trigger avoidance. A woman in her 60s presented with erosive OLP refractory to prednisone and azathioprine. She reported that certain food exposures triggered flares of her OLP. She was subsequently diagnosed with concurrent OAS, and avoidance of food allergens resulted in a clinically significant improvement in her OLP, eventually allowing her to taper off systemic treatment altogether. Further studies are needed to pinpoint common triggers and examine the role of trigger avoidance as a management strategy for OLP. PMID:27663157

  8. Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use

    DEFF Research Database (Denmark)

    Ytting, Henriette; Larsen, Fin Stolze

    2015-01-01

    here report the efficacy of everolimus treatment of patients with AIH. MATERIALS AND METHODS: Seven patients (six female, mean age 47 years, range 22-62 years) in whom disease control could not be achieved with standard therapy or the alternative drugs in use were included. RESULTS: Treatment......OBJECTIVE: Not all patients with autoimmune hepatitis (AIH) respond to standard medical therapy with corticosteroids and azathioprine. Such patients may develop end-stage liver disease with poor prognosis unless transplantation is considered. Alternatively, the introduction of new therapeutic...... with everolimus induced a clear reduction of transaminases within 2 weeks. After 3-5 months three patients had normal alanine aminotransferase (ALT) levels (10-45 IU) and four patients had ALT levels below 55 IU compared to a three- to fivefold elevated level prior to everolimus treatment. Sustained remission...

  9. Current medical therapy of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Kiron M. Das; Sherif A. Farag

    2000-01-01

    The current established drugs used to treat inflammatory bowel disease include glucocorticoids includingnewer agent budesonide, sulfasalazine and 5-ASA compounds such as Asacol, Pentasa, Dipentum andBalsalazide and immunomodulatory agents such as azathioprine, and 6-mercaptopurine. Additional drugswhich have been found to be useful, particularly in refractory cases of Crohn's disease including fistulizingtype of Crohn's disease, include cyclosporine A, methotrexate, humanized antibody against TNFa(cA2),FK506, IL-10, IL-11 and Probiotics. Various agents, whether used alone or in combination, have to betailored for each patient and none is ideal. Exciting new developments directed against proinflammatorypathways, cytokines, free oxygen radicals and cell surface related immune targets are areas of intense recentinvestigations and many novel therapeutic agents are expected to be available in the near future for medicaltreatment of inflammatory bowel disease.

  10. CUTANEOUS NECROTISING VASCULITIS – THERAPEUTIC FACT -A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Kiran

    2012-08-01

    Full Text Available ABSTRACT: INTRODUCTION: Mixed connective tissue disorder, unlike other conn ective tissue disorders have a milder course. MTCD with only nec rotizing cutaneous vasculitis without organ damage respond well to Immunosuppresents and Steroids. CASE REPORT : Middle aged Young lady presented with multiple non healing large pressur e sores and multiple nonblanchable purpuric lesions. She was bedridden, anaemic and wit h significant weight loss. All her major organ functions were normal. Her U 1 RNP Antibody is positive and Skin Biopsy showed positive direct fluorescent test for IgG. She respond ed well to immunosuppresants and steroids. CONCLUSION: This patient who presented with MTCD, with predominant necrotizing cutaneous vasculitis and without major organ involv ement showed good recovery and responded well to cyclophosphamide pulse therapy, daily azathioprine and good wound care

  11. Innovative therapeutics for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jesus K Yamamoto-Furusho

    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 levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade;(4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fawwaz, R.A.

    1984-07-01

    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.

  14. Nifedipine improves immediate, and 6- and 12-month graft function in cyclosporin A (CyA) treated renal allograft recipients.

    Science.gov (United States)

    Harper, S J; Moorhouse, J; Veitch, P S; Horsburgh, T; Walls, J; Bell, P R; Donnelly, P K; Feehally, J

    1992-01-01

    To investigate the effect of oral nifedipine, a calcium channel blocker known not to modify cyclosporin A (CyA) pharmacokinetics, on immediate transplant function and CyA nephrotoxicity, 68 adult renal transplant recipients were pre-operatively randomized to one of three regimes: A (high-dose CyA, initial dose 17 mg/kg per day, maintenance dose 7 mg/kg per day); B (regime A plus oral nifedipine); C low-dose CyA, initial dose 10 mg/kg per day, maintenance 4 mg/kg per day plus azathioprine 1 mg/kg per day). All three groups received identical steroid regimes. Calcium channel blockers of all types were avoided in groups A and C. Delayed graft function (dialysis dependence by day 4) was seen least frequently in group B (P nifedipine significantly improves immediate and medium-term graft function.

  15. Infliximab to treat severe ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Dídia Bisamra Cury; Marcelo de Souza Cury; Geraldo Vinicius Hemerly Elias; Sender Jankiel Mizsputen

    2009-01-01

    A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.

  16. Plasma exchange therapy for a severe relapse of Devic's disease in a pregnant woman: A case report and concise review.

    Science.gov (United States)

    Rubio Tabares, Jonathan; Amaya Gonzalez, Pablo Felipe

    2016-09-01

    Neuromyelitis optica (NMO) or Devic's disease is an autoimmune inflammatory demyelinating condition affecting the central nervous system (CNS). It was initially believed to be a variant of multiple sclerosis (MS). However, the discovery of NMO-IgG anti-AQP4 antibodies marked an objective distinction between these conditions. Treatment of acute attacks is generally based on pulsed steroids, followed by long-term immunosuppression with azathioprine, oral steroids, and rituximab as first-line therapies. Plasma exchange therapy is indicated for steroid-resistant relapses. We describe a case report of a pregnant woman with a severe relapse of Devic's disease, initially misdiagnosed as MS, unresponsive to pulsed steroids, and who underwent plasma exchange therapy safely, with excellent clinical response and with no adverse outcome for the fetus. PMID:27428489

  17. Pro: Cyclophosphamide in lupus nephritis.

    Science.gov (United States)

    Kallenberg, Cees G M

    2016-07-01

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up data available for low-dose pulse cyclophosphamide, the fact that compliance is guaranteed with this regimen and economic issues all favour the Euro-Lupus regimen in this author's opinion. For maintenance treatment, either azathioprine (AZA) or MMF may be used; AZA is preferred in case pregnancy is planned, while MMF is preferred when the disease relapses during use of AZA and, possibly, after successful induction of remission with MMF. PMID:27190359

  18. 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.

  19. Intravenous Immunoglobulin and Mycophenolate Mofetil for Long-Standing Sensory Neuronopathy in Sjögren's Syndrome.

    Science.gov (United States)

    Danieli, Maria Giovanna; Pettinari, Lucia; Morariu, Ramona; Monteforte, Fernando; Logullo, Francesco

    2012-01-01

    Sensory neuronopathy is described in association with the Sjögren's syndrome (SS). We studied a 55-year-old woman with a 4-year history of progressive asymmetric numbness, distal tingling, and burning sensation in upper and lower limbs. In a few months, she developed ataxia with increased hypoanaesthesia. Electrodiagnostic tests revealed undetectable distal and proximal sensory nerve action potential in upper and lower limbs. Cervical spine magnetic resonance showed a signal hyperintensity of posterior columns. Previous treatment with high-dose glucocorticoids and azathioprine was ineffective. A combined treatment with intravenous immunoglobulin and mycophenolate mofetil was followed by a progressive and persistent improvement. This case documented the efficacy and the safety of the coadministration of intravenous immunoglobulin and mycophenolate mofetil in sensory neuronopathy associated with SS refractory to conventional immunosuppressive therapy. PMID:25383230

  20. Crohnology: A tale of time and times and inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Femando Gomollón; Javier P Gisbert; Miquel (A)ngel Gassull

    2008-01-01

    Time, times and timing are key words in inflammatory bowel diseases (IBD).The leifmotif of this issue or World Journal of Gastroenterology is time. We have asked experts to review on the epidemiology of these diseases over time,the changes in innate immunity that could be present in the first time, and then the timing of key treatments. The correct time of using azathioprine, mercaptopurine, infliximab, cyclosporine and surgery are reviewed.We have chosen experts with not only great clinical expertise but also personal interest in clinical and basic investigation. Our goal in this monograph is to get an idea not only of the present but of the immediate future in some of the key management issues in IBD. To this end, we think that the authors are the most adequate.

  1. Clinical utility of thiopurine S-methyltransferase genotyping.

    Science.gov (United States)

    Corominas, Hèctor; Baiget, Montserrat

    2004-01-01

    Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that plays a major role in the metabolism of thiopurine drugs such as mercaptopurine and azathioprine. The interindividual differences in response to thiopurine administration is in part due to the presence of genetic polymorphisms in the gene that regulates TPMT activity. TPMT genotype correlates well with the in vivo enzyme activity within erythrocytes. Patients with genetically determined decreased TPMT activity develop severe myelosuppression when treated with standard doses of thiopurine drugs because an excess of thioguanine nucleotides accumulates in hematopoietic tissues. TPMT genotyping provides clinicians with a reliable method for identifying TPMT-deficient patients who can benefit from low doses of thiopurine drugs in order to reduce the risk of developing adverse effects. Moreover, the administration of higher doses of the drug could improve therapeutic response in patients in whom the TPMT genotyping demonstrates the absence of mutated alleles.

  2. Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jamie B Sodikoff; Steven A Keilin; Qiang cai; Sheila J Bharmal; Melinda M Lewis; Gottumukkala S Raju; Field F Willingham

    2012-01-01

    Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis; however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

  3. Themes of liver transplantation.

    Science.gov (United States)

    Starzl, Thomas E; Fung, John J

    2010-06-01

    Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation

  4. Anti-TNF treatment and miliary tuberculosis in Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Milenković Branislava

    2011-01-01

    Full Text Available Introdution. Tumour necrosis factor alpha (TNFα has a central role in the host immune response to mycobacterial infection. TNFα blockade may therefore result in reactivation of recent or remotely acquired infection. In reported mycobacterium tuberculosis infections, extra-pulmonary and disseminated tuberculosis (TB was common, appeared rapidly, and if unrecognized, with fatal outcome. We present a female patient with miliary TB following treatment with infliximab for fistulizing Crohn’s disease. Case Outline. Five years before admission, the patient was diagnosed with Crohn’s disease, with inflammation limited to the terminal ileum and sigmoid colon and has been on azathioprine 100 mg/day for the last 10 months. Three months before admission to the hospital she developed an enterocutaneous fistula for which therapy with infliximab was started in addition to azathioprine therapy. A tuberculin skin test and a chest x-ray were performed prior to the first infusion with normal findings. She presented with a 6-week history of fever, weakness, weight-loss and a 2-week dry cough. Chest x-ray and computed tomography displayed remarkable bilateral hilar and mediastinal lymphadenopathy and uniformly distributed fine nodules throughout both lung fields varying in size from 2 to 3 mm, without any signs of cavitation. Since there were clinical and morphological signs that indicated miliary TB, the treatment with antituberculous therapy was started and six weeks later all of the symptoms completely resolved and the lesions visible on x-ray diminished. Conclusion. The clinical use of TNF-inhibitors is associated with increased risk of developing tuberculosis. Physicians should be aware of the increased risk of reactivation of TB among patients treated with anti-TNF agents and regularly look for usual and unusual symptoms of TB.

  5. 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.

  6. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2015-01-01

    Full Text Available Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants. Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators. The following terms were used: "inflammatory bowel disease (IBD" OR "Crohn′s disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine" AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]" AND "immunomodulators." Study Selection: The inclusion criteria of articles were that the studies: (1 Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria; (2 exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3 exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents. The exclusion criteria of articles were that the studies: (1 History of hepatitis B virus (HBV, influenza or streptococcus pneumoniae infection; (2 patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3 any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection; (4 individuals with positive hepatitis markers or liver cirrhosis; (5 patients with a known allergy to eggs or other components of the vaccines and (6 pregnancy. Results: Patients treated with immunomodulators were associated with lower response rates to

  7. 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. PMID:27108360

  8. Successful pregnancy in pulmonary arterial hypertension associated with systemic lupus erythematosus: a case report

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    Streit Michael

    2009-06-01

    Full Text Available Abstract Introduction Pulmonary arterial hypertension is a complication of systemic lupus erythematosus. Mortality in pregnant patients with pulmonary arterial hypertension related to connective tissue disease is as high as 56%. The authors report the first case of a successful maternal-fetal outcome in a pregnant patient with systemic lupus erythematosus-associated pulmonary arterial hypertension treated with sildenafil and inhaled iloprost during pregnancy and until several weeks after caesarean section. Case presentation The case presented is of a 29-year-old woman with systemic lupus erythematosus and associated severe pulmonary arterial hypertension. Vasodilator therapy with bosentan and sildenafil, immunosuppressive therapy with prednisone, hydroxychloroquine and azathioprine and oral anticoagulation (phenprocoumon had normalized her right ventricular over right atrial pressure when she was diagnosed in her 5th week of pregnancy. The teratogenic drugs bosentan and phenprocoumon were stopped, the latter replaced by low molecular weight heparin. During the 35th week, a slight increase in pulmonary pressure was found. Therapy with inhaled iloprost was established. A caesarean section was performed in the 37th week and a healthy baby was delivered. The patient remained stable until 11 weeks after delivery, when an increase in right ventricular over right atrial pressure was noted. Bosentan was reintroduced and prednisone and azathioprine doses were increased. The patient has remained stable until the present time. Conclusion Pulmonary arterial hypertension has been considered a contraindication for pregnancy. Novel vasodilator therapy, combined with immunosuppressants in this patient with systemic lupus erythematosus, may "cure" pulmonary arterial hypertension and permit pregnancy with successful outcome. However, postpartum exacerbation of systemic lupus erythematosus and pulmonary arterial hypertension have to be considered.

  9. Treatment of severe steroid refractory ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Gert Van Assche; Séverine Vermeire; Paul Rutgeerts

    2008-01-01

    Although systemic steroids are highly efficacious in ulcerative colitis (UC),failure to respond to steroids sUll poses an important challenge to the surgeon and physician alike. Even if the life Lime risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled),infliximab (5 mg/kg N,0-2-6 wk) or total colectomy.The choice between these three options is a medicalsurgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin).Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy).The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore,patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.

  10. Treatment of severe steroid refractory ulcerative colitis

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    Assche, Gert Van; Vermeire, Séverine; Rutgeerts, Paul

    2008-01-01

    Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg IV, 0-2-6 wk) or total colectomy. The choice between these three options is a medical-surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections. PMID:18810767

  11. 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.

  12. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

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    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective:To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants).Data Sources:We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators).The following terms were used:"inflammatory bowel disease (IBD)" OR "Cmhn's disease" OR "ulcerative colitis"AND ("vaccination" OR "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]") AND "immunomodulators."Study Selection:The inclusion criteria of articles were that the studies:(1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical,radiographic,endoscopic,and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping,15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy,antibiotics only,mesalazine only,biological agent only such as infliximab,adalimumab,certolizumab or natalizumab or within 3 months of stopping one of these agents).The exclusion criteria of articles were that the studies:(1) History of hepatitis B virus (HBV),influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV,influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g.chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy.Results:Patients treated with immunomodulators were associated with lower response rates to vaccination

  13. Co occurrence of Hepatitis B Virus Infection and Autoimmune Hepatitis with Marked Hepatitis B Virus Replication Following Treatment of Autoimmune Hepatitis

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    Tyagi I

    2015-10-01

    Full Text Available Background: Children have different natural history of Hepatitis B virus (HBV infection. They commonly develop asymptomatic chronic carrier state which is less frequently seen in adults. We describe a rare case of acute on chronic liver failure (ACLF in the course of concurrent autoimmune hepatitis (AIH and HBV infection and replication of HBV following the treatment for autoimmune hepatitis. Case Report: A 15 year old male child presented with jaundice and altered sensorium. Physical examination showed hepatosplenomegaly. The liver function tests were markedly altered. Serology was positive for anti liver kidney microsomal antibody (LKM, hepatitis B surface antigen (HBsAg and immunoglobulin M (IgM anti hepatitis B core antigen (HBc Ag. Liver biopsy showed chronic hepatitis with features of acute exacerbation. Patient was started on treatment with azathioprine and prednisolone for AIH following which clinical and biochmemical improvement was noted. After two years of continued treatment a repeat biopsy performed showed fairly reduced histological activity, but marked replication of the HBV (immunohistochemistry for HBsAg and anti HBcAg showed diffuse cytoplasmic and nuclear positivity respectively. These findings suggest viral replication although the patient was clinically stable. At six months follow-up after the second biopsy and cessation of azathioprine and prednisolone, there were raised liver enzymes and viral load, hence the patient was started on antiviral drug Entecavir to which there was good response and the patient is presently doing well. Conclusion: We describethe rare co occurrence of HBV infection and AIH with marked HBV replication following the treatment for AIH

  14. Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

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    Vaskonen, T; Mervaala, E; Nevala, R; Soots, A; Krogerus, L; Lähteenmäki, T; Karppanen, H; Vapaatalo, H; Ahonen, J

    2000-01-01

    The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

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

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    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.

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

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    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.

  17. [A case report of childhood systemic lupus erythematosus complicated with lupus cystitis].

    Science.gov (United States)

    Kurosawa, Rumiko; Miyamae, Takako; Imagawa, Tomoyuki; Katakura, Shigeki; Mori, Masaaki; Aihara, Yuhkoh; Yokota, Shumpei

    2006-06-01

    The patient was a 13-year-old girl. In August 2000, she presented with a fever, together with diarrhea, vomiting, arthralgia, nasal bleeding and malaise, and was examined by another physician. Because her platelet count was low, and there were positive reactions for anti-nuclear antibodies, anti-DNA antibodies and platelet-associated IgG, idiopathic thrombopenic purpura, and systemic lupus erythematosus (SLE) was suspected. From January 2001, when she caught measles, she reported abdominal pain, and urinalysis indicated urinary protein and occult blood, and the left kidney was found hydronephrotic. At the same time left ureter stenosis and dilatation were demonstrated. Symptoms were disappeared by hydration and treatment with NSAIDs, but 2 months later fever and erythematous patches seen on both cheeks led to the proper diagnosis of SLE, and she was admitted to our hospital. Intravenous pyelography revealed hydronephrosis on left kidney, constriction and dilatation of the left ureter, and intracystic endoscopy showed erythema at the orifice of the left ureter. The pathological examination indicated the presence of vasculitis, and finally lupus cystitis was diagnosed. Intravenous cyclophosphamide (IVCY)-pulse therapy was introduced to a total of 8 times over the period of a year, and maintenance therapy with predonisolone and azathioprin was also used. After completion of the IVCY-pulse therapy, the hydronephrosis and constriction of the ureter were disappeared. No side effects of IVCY-pulses were observed, and the patient is now in remission. We reported a case of childhood SLE complicated with lupus cystitis and successfully treated by IVCY-pulse therapy and maintenance predonisolone and azathioprin.

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

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    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.

  19. Medical management of chronic liver diseases in children (part I): focus on curable or potentially curable diseases.

    Science.gov (United States)

    El-Shabrawi, Mortada H F; Kamal, Naglaa M

    2011-12-01

    The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic

  20. Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis

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    van Bodegraven Adriaan A

    2011-05-01

    Full Text Available Abstract Background Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG and azathioprine (AZA in a murine model of IBD. Methods We induced acute or chronic colitis in BALB/c mice by one or four cycles of 3% dextran sulphate sodium (DSS, respectively. Mice were treated by daily gavages of various dosages of 6-tioguanine, azathioprine, or by phosphate buffered saline (PBS starting the first day of DSS or after two cycles of DSS, respectively. We monitored the efficacy and toxicity by measuring the weight change and serum alanine aminotransferase (ALT activity and by disease severity and histology, at the end of the experiment. Moreover, we measured cytokine production after colon fragment cultivation by enzyme-linked immunoabsorbent assay and numbers of apoptotic cells in the spleen by flow cytometry. Results 6-TG is effective in the treatment of acute DSS-induced colitis in a dose-dependent manner and 40 μg of 6-TG is significantly more effective in the treatment of acute colitis than both AZA and PBS. This effect is accompanied by decrease of IL-6 and IFN-γ production in colon. We did not observe histological abnormalities in liver samples from control (PBS or 6-TG treated mice. However, liver samples from most mice treated with AZA showed mild, yet distinct signs of hepatotoxicity. In chronic colitis, all thiopurine derivatives improved colitis, 20 μg of 6-TG per dose was superior. High doses of 6-TG led to significant weight loss at the end of the therapy, but none of the thiopurine derivatives increased levels of serum ALT. Both thiopurine derivatives reduced the proportion of apoptotic T helper cells, but a high production of both IL-6 and TGF-β was observed only in colon of AZA-treated mice. Conclusions Use of 6-TG in the treatment

  1. Gout in solid organ transplantation: a challenging clinical problem.

    Science.gov (United States)

    Stamp, Lisa; Searle, Martin; O'Donnell, John; Chapman, Peter

    2005-01-01

    Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor. Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined. Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with

  2. 355 Ocular Muscles Myopathy Associated with Autoimmune Thyroiditis. Case Reports

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    Vargas-Camaño, Eugenia; Castrejon-Vázquez, Isabel; Plazola-Hernández, Sara I.; Moguel-Ancheita, Silvia

    2012-01-01

    Background Thyroid-associated orbitopathy is commonly associated with Graves' disease with lid retraction, exophthalmos, and periorbital swelling, but rarely with autoimmune thyroiditis or euthyroid state. We reviewed 3 cases from our hospital whose antibodies to anti-receptor of TSH were normal. Methods Case 1: 60 year-old non-diabetic woman with bilateral glaucoma in treatment, recurrent media otitis and euthyroidism, acute onset of painless diplopia, and lid ptosis in the left eye. MRI of orbit showed increased size of the III right cranial pair and high levels of thyroid autoantibodies (Tab) anti-tiroglobulin (ATG) 115.1, anti-thyroid peroxidase (ATPO) 1751 U/mL. She started oral deflazacort 30 mg each 3 days. Sixty days later, complete remission of eye symptoms correlated with lower auto-antibodies level (ATG 19 ATPO 117). Case 2: 10 year-old girl. At age 8, she had diplopia, lid ptosis and limitations of upper gaze in the left eye. The neurological study discarded ocular myasthenia; with thyroid goitier, and hypothyrodism, she started oral levothyroxin. At age 10 with normal IRM Botulinic toxin was injected, without change. High levels of Tab were found, ATG 2723, ATPO 10.7. She started oral deflazacort 30 mg each 3 days, azathioprin 100 mg, daily. Actually, Tab levels are almost normal, but she remains with ocular alterations. Case 3: 56 year-old woman, Grave´s disease with exophtalmos in 1990, treated with I131 and immunosupression, with good outcome; obesity, hypertension and bilateral glaucoma in treatment. She suddenly presented diplopia and IV pair paresia of the right eye. A year later, ATb were found slightly elevated, ATG 100 years ATPO 227; despite prednisone 50 mg, each 3 days and azathioprin 150 mg/daily treatment, a surgical procedure was required for relieve the ocular symptoms. Results We found only 3 cases previously reported with this type of eye thyroid disease. Is important to note that awareness of this atypical form of orbitopathy

  3. [Cutaneous nocardiosis as an opportunistic infection].

    Science.gov (United States)

    Bogaard, H J; Erkelens, G W; Faber, W R; de Vries, P J

    2004-03-13

    A 46-year-old man who had been treated with azathioprine and budesonide for Crohn's disease for the past eight years developed a purulent skin condition on the right ring finger. Despite surgical drainage and treatment with amoxicillin and flucloxacillin, the condition spread itself over the hand and lower arm, partly per continuum and partly in jumps. The patient did not feel ill and there were no systemic symptoms. Ultimately, Nocardia asteroides was cultured from the wound and complete cure was achieved after 8 months' treatment with co-trimoxazole. Infections with Nocardia spp. are rare but may occur more often and run a more fulminant course in patients under treatment with immunosuppressants. Cutaneous nocardiosis generally has a characteristic lymphogenous spreading pattern, but an atypical picture with pustules, pyoderma, cellulitis or abscess formation is also possible. In non-cutaneous nocardiosis there is usually pneumonia or lung abscess, possibly with secondary haematogenous spread to the central nervous system or skin. Culturing Nocardia requires more time than usual but can be promoted by special culture media. Treatment of the infection with co-trimoxazole is the method of choice and is almost always successful in cases of cutaneous nocardiosis.

  4. The management of hypophysitis.

    Science.gov (United States)

    Karaca, Zuleyha; Kelestimur, Fahrettin

    2016-09-01

    Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either primary or secondary. In this review, treatment of primary hypophysitis of various histological subtypes are discussed. Management of primary hypophysitis is usually symptomatic aiming to reduce the size of the pituitary mass and/or replace deficient pituitary hormones. Observation with replacement for deficient pituitary hormones can be applied in some group of patients. Keeping the complications of surgery in mind, surgical intervention should be limited to cases with severe and/or deteriorating compressive signs or cases with inconclusive findings of hypophysitis in whom treatment would be based on histopathological examination. The most commonly used drugs in the treatment of hypophysitis are glucocorticoids. They are able to reduce the size of the mass lesion with their anti-inflammatory effects and sometimes pituitary functions may also recover. However, there is no consensus about the optimal duration and dose of glucocorticoid use. When glucocorticoids and/or surgery fail, azathioprine, methotrexate, cyclosporin A and novel immunotherapies can be tried as third or forth line treatment. Radiotherapy and radiosurgery have been seldom used for treatment of hypophysitis in order to reduce the mass effect. PMID:26963662

  5. Chronic intestinal pseudo-obstruction as an expression of inflammatory enteric neuropathy

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    Rita Pimentel

    2014-11-01

    Full Text Available Chronic intestinal pseudo-obstruction (CIPO is characterised by inadequate digestive tract motility and can lead to severely disordered motility. CIPO manifests as recurrent episodes of intestinal sub-occlusion without an anatomical obstruction. We present the case of a 41-year-old female, with severe chronic constipation and several episodes of intestinal sub-occlusion. Investigation revealed colonic inertia and marked distension of the small bowel and colon with no evidence of stenosis or obstructive lesions, compatible with CIPO. After several treatments were tried (domperidone, erythromycin, cisapride, octreotide, total enteral nutrition, with partial or no response, further work-up was done trying to identify an etiology. Gastrointestinal manometry showed neuropathic type abnormalities, transmural biopsy of the jejunum revealed degenerative enteric neuropathy and anti-HU antineuronal antibody screen was positive, suggesting an autoimmune type neuropathy with diffuse involvement of the digestive tract. Corticosteroids showed partial improvement of short duration and azathioprine was also tried but discontinued due to intolerance. Marked dietary intolerance and malnutrition lead to total parenteral nutrition (TPN at home since October 2011. Since then, symptoms and nutritional status improved, with rare episodes of pseudo-obstruction, not requiring hospitalisation.

  6. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy

    Institute of Scientific and Technical Information of China (English)

    María Luisa Manzano-Alonso; Gregorio Castellano-Tortajada

    2011-01-01

    Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus (HBV) replication,often accompanied by an increase in serum transaminase levels, and both events occurring in a patient with a previous inactive hepatitis B infection. This reactivation can occur in situations in which the ratio of HBV replication and immune response is altered. It can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune diseases. Clinical manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis, which are sometimes serious and result in acute liver failure with risk of death, and usually occur in the periods between cycles or at the end of chemotherapy. Immunosuppressive drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen (HBsAg) or anti-HBc, but much less frequently than chemotherapy treatments. The tumor necrosis factor α inhibitors infliximab, etanercept and adalimumab may cause reactivation of hepatitis B, and the overall frequency with infliximab may be similar (50%-66%) to that caused by chemotherapy. Baseline HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs, and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.

  7. Noninfectious interstitial lung disease during infliximab therapy: case report and literature review.

    Science.gov (United States)

    Caccaro, Roberta; Savarino, Edoardo; D'Incà, Renata; Sturniolo, Giacomo Carlo

    2013-08-28

    Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases. However, lung toxicity can be induced by conventional medications used to maintain remission, and similar evidence is also emerging for biologics. We present the case of a young woman affected by colonic Crohn's disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab. She was referred to our clinic with a severe relapse and was treated with infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, to induce remission. After an initial benefit, with decreases in bowel movements, rectal bleeding and C-reactive protein levels, she experienced shortness of breath after the 5(th) infusion. Noninfectious interstitial lung disease was diagnosed. Both mesalamine and infliximab were discontinued, and steroids were introduced with slow but progressive improvement of symptoms, radiology and functional tests. This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations. Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases, this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.

  8. Epidemiology and clinical course of Crohn's disease: Results from observational studies

    Institute of Scientific and Technical Information of China (English)

    φistein Hovde; Bjφrn A Moum

    2012-01-01

    The authors review the clinical outcome in patients with Crohn's disease (CD) based on studies describing the natural course of the disease.Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s.The authors search for English language articles from 1980 until 2011.Geographical variations,incidence,prevalence,smoking habits,sex,mortality and medications are investigated.An increasing incidence and prevalence of CD have been found over the last three decades.The disease seems to be most common in northern Europe and North America,but is probably increasing also in Asia and Africa.Smoking is associated with an increased risk of developing CD.Age < 40 at diagnosis,penetrating/stricturing complications,need for systemic steroids,and disease location in terminal ileum are factors associated with higher relapse rates.A slight predominance of women diagnosed with CD has been found.Ileocecal resection is the most commonly performed surgical procedure,and within the first five years after the diagnosis about one third of the patients have had intestinal surgery.Smoking is associated with a worse clinical course and with increased risk of flare-ups.In most studies the overall mortality is comparable to the background population.To date,the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-α-blockers.Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    D’Amico, Emanuele; Leone, Carmela; Graziano, Giusi; Amato, Maria Pia; Bergamaschi, Roberto; Cavalla, Paola; Coniglio, Gabriella; Di Battista, Giancarlo; Ferrò, Maria Teresa; Granella, Franco; Granieri, Enrico; Lugaresi, Alessandra; Lus, Giacomo; Millefiorini, Enrico; Pozzilli, Carlo; Tedeschi, Gioacchino; Zappia, Mario; Comi, Giancarlo; Trojano, Maria; Lepore, Vito; Patti, Francesco

    2016-01-01

    Introduction 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? Methods 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. Results 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). Conclusions Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population. PMID:27348606

  12. A severe Whipple disease with an immune reconstitution inflammatory syndrome: an additional case of thalidomide efficiency.

    Science.gov (United States)

    Le Blay, Pierre; Rakotonirainy, Henintsoa; Lagier, Jean-Christophe; Raoult, Didier; Puechal, Xavier; Pers, Yves-Marie

    2014-05-01

    We report the case of a 38-year-old man who presented with severe diarrhea, weight loss of 10 kg, ankles paresthesia and severe motor weakness in the left fibular nerve territory after introduction of azathioprine and corticosteroid for proteinuria. Coloscopy and gastroscopy revealed a typical aspect of Whipple disease (WD), associated with both positive PAS staining and specific immunohistochemistry. T. whipplei PCR results were positive in blood, faeces, saliva and duodenal biopsy specimens. Diagnosis of WD with systemic manifestations was retained and doxycycline plus hydroxychloroquine therapy were started. This treatment improved joint pain, and skin and intestinal symptoms. One month later, our patient presented with fever and an important inflammatory syndrome (CRP 150 mg/dL and 16.8 10(9)/L leukocytes), while no infection was found despite a thorough review. We concluded it was an immune reconstitution inflammatory syndrome (IRIS). Manifestations persisted despite increasing corticosteroids and thalidomide (200 mg/day) was introduced with good efficacy on these symptoms. WD may be revealed by non-specific symptoms such as weight loss or arthralgia, but also by many other misleading signs. Our observation illustrates the highly polymorphic clinical presentation of WD, and the diagnostic difficulties that may arise. This is also a new report of thalidomide effectiveness in IRIS in WD.

  13. Golimumab in unresponsive ulcerative colitis

    Directory of Open Access Journals (Sweden)

    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

  14. Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review.

    Science.gov (United States)

    Salama, Abdulgabar

    2015-09-01

    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.

  15. Atualização do tratamento das vasculites associadas a anticorpo anticitoplasma de neutrófilos Treatment of antineutrophil cytoplasmic antibody-associated vasculitis: update

    Directory of Open Access Journals (Sweden)

    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.

  16. Hepatotoxicity associated with cyclosporine monitoring using C2 recommendations in adults renal recipients receiving ketoconazole.

    Science.gov (United States)

    Videla, C; Vega, J; Borja, H

    2005-04-01

    Following the change, in the way we monitored cyclosporine (CsA) levels in January 2000 namely from C0 to C2 concentrations, in renal "de novo" allograft recipients, some patients treated with concomitant ketoconazole experienced liver toxicity, a complication that had not been previously seen with CsA monitoring using C0. Therefore, we decided to compare the outcomes of patients transplanted using CsA levels monitored by C0 (1998 to 1999) who also had simultaneous C2 determinations (group A) with those of recipients transplanted after 2000 (group B). All received steroids, azathioprine, and CsA plus ketoconazole. Recipients were followed for at least a year after transplantation. Patients in group B showed higher CsA C2 levels, AUC concentrations, and drug doses during the immediate postsurgical period, and at 2 weeks as well as 4 and 6 months posttransplantation. Six group B patients (26%) but no group A recipients displayed, severe liver toxicity characterized by jaundice, elevated liver enzymes, with negative serological tests for CMV, HVC, and HVB. There was a correlation between the GOT and the C2 CsA levels; both normalized 15 to 55 days after CsA dose reduction. High C2 CsA levels, which have been recommended when the drug is used alone in renal transplantation, cannot be used in patients taking ketoconazole, because C2 neither represents nor correlates with AUC drug exposure. Thus high C2 levels may produce liver toxicity. PMID:15866677

  17. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    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

  18. Acute Pancreatitis due to pH-Dependent Mesalazine That Occurred in the Course of Ulcerative Colitis

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    Yoshinori Arai

    2011-10-01

    Full Text Available We report the case of a 26-year-old male who presented with acute pancreatitis during the course of treatment for pancolitic ulcerative colitis (UC with a time-dependent mesalazine formulation, prednisolone and azathioprine (AZA. Despite a review of his clinical history and various tests, the cause of pancreatitis could not be determined. Since drug-induced pancreatitis was considered possible, administration of the time-dependent mesalazine preparation and AZA was discontinued, and conservative treatment for acute pancreatitis was performed. The pancreatitis promptly improved with these treatments, but drug lymphocyte stimulation test (DLST for both the time-dependent mesalazine formulation and AZA was negative. A pH-dependent mesalazine formulation was given for maintenance therapy of UC. Subsequently, as the pancreatitis relapsed, drug-induced pancreatitis was strongly suspected. Administration of mesalazine was discontinued, and pancreatitis was smoothly in remission by conservative treatment. According to the positive DLST result for the pH-dependent mesalazine formulation and the clinical course, a diagnosis of pH-dependent mesalazine-induced pancreatitis due to this formulation was made. During the clinical course of UC, occurrence of drug-induced pancreatitis must always be considered.

  19. 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 ...

  20. HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

  1. 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.

  2. Bimonthly Evolution of Cortical Atrophy in Early Relapsing-Remitting Multiple Sclerosis over 2 Years: A Longitudinal Study

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    Robert Zivadinov

    2013-01-01

    Full Text Available We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR multiple sclerosis (MS and its association with lesion volume (LV accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD at baseline of ≤24 months were classified in the early group (DD of 1.2 years, n=37, while patients with DD > 24 months were classified in the late group (DD of 7.1 years, n=99. Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV (P<0.001, cortical volume (CV (P<0.001, and in T2-LV (P<0.001 were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P<0.01. No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P=0.01. Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.

  3. 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.

  4. Pregnancy in Systemic Lupus Erythematosus Patients with Nephritis

    Directory of Open Access Journals (Sweden)

    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.

  5. The Outlier in All of Us: Why Implementing Pharmacogenomics Could Matter for Everyone.

    Science.gov (United States)

    O'Donnell, P H; Danahey, K; Ratain, M J

    2016-04-01

    The field of pharmacogenomics originally emerged in the 1950s from observations that a few rare individuals had unexpected, severe reactions to drugs. As recently as just 6 years ago, prominent views on the subject had largely remained unchanged, with authors from the US Food and Drug Administration (FDA) citing the purpose of pharmacogenetics as "tailoring treatment for the outliers." It should not be surprising if this is the prevailing view--the best-studied pharmacogenomic drug examples are indeed just that, genetic explanations of extreme responses or susceptibilities among usually a very small fraction of the human population. Thiopurine methyltransferase (TPMT) deficiency as a cause of severe myelosuppression upon treatment with azathioprine or mercaptopurine is found as a heterozygous trait in only ∼ 10% of patients, and homozygous (deficiency) carriers are even more rare--occurring in fewer than 1 in 300 patients. Malignant hyperthermia resulting from inhaled anesthetics and succinylcholine is believed to have a genetic incidence of only about 1 in 2000 people.

  6. Overlap syndromes among autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Christian Rust; Ulrich Beuers

    2008-01-01

    The three major immune disorders of the liver are autoimmune hepatitis (AIH),primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.

  7. [Lupus nephritis: up-to-date].

    Science.gov (United States)

    Karras, A

    2015-02-01

    Renal involvement is frequent during natural history of systemic lupus erythematosus (SLE) and has a major prognostic value in this systemic disease. Screening for renal symptoms, such as proteinuria, micro-haematuria or renal failure must be performed at initial diagnosis and repeated during subsequent follow-ups. Any significant abnormality of these parameters may reveal active glomerulonephritis (GN) and should lead to a renal biopsy, which will significantly impact the therapeutic choices. Proliferative GN, defined as class III or IV by the actual histo-pathological classification, is the most severe form of SLE-associated nephropathy and can lead to end-stage renal disease (ESRD) in up to 60% of cases, according to ethnicity and follow-up duration. Standard induction treatment of active proliferative GN includes corticosteroids combined with an immunosuppressive drug, which can either be cyclophosphamide or mycophenolate mofetil (MMF). Even though, recent biotherapies have not yet proved their efficacy in the field of lupus nephritis, new protocols are expected, aiming higher remission rates and avoidance of high-dose corticosteroids regimens. When remission is achieved in proliferative GN, a maintenance therapy is required to decrease the risk of relapse, using either azathioprine or MMF. Immunosuppressive drugs are responsible for an increased risk of infectious or neoplastic complications but cardiovascular disease is actually one of the main causes of mortality among lupus patients, especially for patients with SLE-related kidney disease, well before reaching ESRD.

  8. [A study on inclusion complexes of cyclodextrin with three anticancer xanthines by fluorescence].

    Science.gov (United States)

    Wei, Yan-li; Dong, Chuan

    2004-07-01

    The inclusion complexes of beta-Cyclodextrin (beta-CD) and HP-beta-Cyclodextrin (HP-beta-CD) with 6-Mercaptopurine (6-MP), Azathioprine (BAN) and 8-Azaguanine (Azan) were investigated by fluorescence. Various factors affecting the formation of inclusion complexes were discussed in detail including formation time and pH effect. The formation constants of their inclusion complexes were determined. The results indicated that their inclusion was affected significantly by laying time and pH. The formation time of beta-CD inclusion complexes is much longer than that of HP-beta-CD. The optimum pH is about pH = 7.7-12. Their maximum excitation wavelengths are all in the range of 276-285 nm and the maximum emission wavelengths are all in the range of 328-353 nm. The fluorescence signals are intensified with increasing concentration of CD. The stoichiometries of the inclusion complexes of CD with these three anticancer xanthines are all 1:1 and the formation constants are calculated.

  9. Survival in sensitized lung transplant recipients with perioperative desensitization.

    Science.gov (United States)

    Tinckam, K J; Keshavjee, S; Chaparro, C; Barth, D; Azad, S; Binnie, M; Chow, C W; de Perrot, M; Pierre, A F; Waddell, T K; Yasufuku, K; Cypel, M; Singer, L G

    2015-02-01

    Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long-term lung transplant outcomes. We implemented a perioperative strategy to treat DSA-positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens. DSA-positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA-positive/DSA-negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011, 340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA-positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96% in the three groups, respectively. One-year graft survival was 89%/88%/86% (p = 0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA-positive patients, with similar outcomes to unsensitized recipients. PMID:25612494

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. Idiopathic portal hypertension in renal transplant recipients: report of two cases.

    Science.gov (United States)

    Yoshimura, N; Oka, T; Ohmori, Y; Yasumura, T; Kohnosu, H; Kobashi, T

    1994-01-01

    We present herein the cases of two patients who developed idiopathic portal hypertension (IPH) following renal transplantation. Both patients had been treated with azathioprine and prednisolone for 6 years and 4 months and for 4 years and 7 months, respectively, and presented with splenomegaly and thrombocytopenia suggesting hypersplenism. Celiac angiography showed a dilated splenic artery and vein in both patients. When the splenic artery was obliterated with a balloon catheter in case 1, the portal venous pressure decreased from 51 cmH2O to 36 cmH2O, and the direction of the superiomesenteric venous blood flow became hepatopetal rather than hepatofugal. These results suggested that the spleen might have played an important role in the development of IPH in these two patients. A splenectomy was therefore performed, immediately following which the portal venous pressure decreased remarkably, and the esophageal varices disappeared during the postoperative follow-up period. Microscopic examination of liver biopsies taken at the operation revealed lymphoplasmacytic infiltration with bile duct hyperplasia but no evidence of periportal fibrosis, and electron microscopy demonstrated very mild perisinusoidal fibrosis. Thus, the histological changes seen in the livers of these patients seemed not to have caused the portal hypertension. In conclusion, although few patients develop IPH after renal transplantation, we should be aware of its possibility and consider splenectomy as the treatment of choice.

  12. IgG4-Related Disease Presenting as Recurrent Mastoiditis With Central Nervous System Involvement

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    April L. Barnado MD

    2013-09-01

    Full Text Available We report a case of a 43-year-old female who presented with right ear fullness and otorrhea. She was initially diagnosed with mastoiditis that was not responsive to multiple courses of antibiotics and steroids. She was then diagnosed with refractory inflammatory pseudotumor, and subsequent treatments included several mastoidectomies, further steroids, and radiation therapy. The patient went on to develop mastoiditis on the contralateral side as well as central nervous system involvement with headaches and right-sided facial paresthesias. Reexamination of the mastoid tissue revealed a significantly increased number of IgG4-positive cells, suggesting a diagnosis of IgG4-related disease. The patient improved clinically and radiographically with rituximab and was able to taper off azathioprine and prednisone. IgG4-related disease should be considered in patients with otologic symptoms and be on the differential diagnosis in patients with inflammatory pseudotumor. Staining for IgG and IgG4 is essential to ensure a prompt diagnosis and treatment.

  13. Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

    Institute of Scientific and Technical Information of China (English)

    Li-Juan Huang; Qin Zhu; Min Lei; Qian Cao

    2009-01-01

    AIM: To investigate immunosuppressive agents used to treat inflammatory bowel disease (IBD) in East China. METHODS: A retrospective review was conducted, involving 227 patients with IBD admitted to Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University from June 2000 to December 2007. Data regarding demographic, clinical characteristics and immunosuppressants usage were analyzed. RESULTS: A total of 227 eligible patients were evaluated in this study, including 104 patients with Crohn's disease and 123 with ulcerative colitis. Among the patients, 61 had indications for immunosuppressive agents use. However, only 21 (34.4%) received immunosuppressive agents. Among the 21 patients, 6 (37.5%) received a subtherapeutic dose of azathioprine with no attempt to increase the dosage. Of the 20 patients that received immunosuppressive agent treatment longer than 6 mo, 15 patients went into remission, four patients were not affected and one relapsed. Among these 20 patients, four patients suffered from myelotoxicity and one suffered from hepatotoxicity. CONCLUSION: Immunosuppressive agents are used less frequently to treat IBD patients from East China compared with Western countries. Monitoring immunosuppressive agent use is recommended to optimize dispensation of drugs for IBD in China.

  14. Successful Discontinuation of Infliximab in a Refractory Case of Vasculo-Behçet Disease

    Directory of Open Access Journals (Sweden)

    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.

  15. 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. PMID:24572296

  16. Pharmacogenetics in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Marie Pierik; Paul Rutgeerts; Robert Vlietinck; Severine Vermeire

    2006-01-01

    Pharmacogenetics is the study of the association between variability in drug response and (or) drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient's specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases (IBD), ulcerative colitis (UC),and Crohn's disease (CD) including sulfasalazine and mesalazine, azathioprine (AZA) and 6-mercaptopurine (6-MP), methotrexate (MTX), glucocorticosteroids (CSs) and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase (TPMT) gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Interstitial lung disease in patients with rheumatoid arthritis: spontaneous and drug induced.

    Science.gov (United States)

    Hallowell, Robert W; Horton, Maureen R

    2014-03-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by the destruction of articular joint structures. RA is a systemic condition that often affects multiple organs, including the heart, lungs, and kidneys. Pulmonary complications of RA are relatively common and include pleural effusion, rheumatoid nodules, bronchiectasis, obliterative bronchiolitis, and opportunistic infections. Interstitial lung disease (ILD) is a common occurrence in patients with RA, and can range in severity from an asymptomatic incidental finding to a rapidly progressing life-threatening event. Usual interstitial pneumonia and non-specific interstitial pneumonia are the two most common patterns, though others have been reported. Various disease-modifying anti-rheumatic drugs-in particular, methotrexate and the tumor necrosis factor-alpha inhibitors-have been associated with RA-ILD in numerous case reports and case series, though it is often difficult to distinguish association from causality. Treatment for RA-ILD typically involves the use of high-dose corticosteroids, often in conjunction with alternative immunosuppressant agents such as azathioprine or mycophenolate mofetil, and outcomes vary widely depending on the initial pattern of lung disease. Additional research into the mechanisms driving RA-ILD is needed to guide future therapy.

  19. 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.

  20. 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.

  1. Morvan Syndrome: A Case Report With Patient Narrative and Video.

    Science.gov (United States)

    Maskery, Mark; Chhetri, Suresh K; Dayanandan, Rejith; Gall, Claire; Emsley, Hedley C A

    2016-01-01

    A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management.

  2. Therapeutic advances and future prospects in immune-mediated inflammatory myopathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2008-11-01

    THE INFLAMMATORY MYOPATHIES INCLUDE THREE DISTINCT ENTITIES: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). A T-cell-mediated cytotoxic process in PM and IBM and a complement-mediated microangiopathy in DM are the hallmarks of the underlying autoimmune processes. The most consistent therapeutic problem remains the distinction of PM from the difficult-to-treat mimics such as s-IBM, necrotizing myopathies and inflammatory dystrophies. This review provides a step-by-step approach to the treatment of inflammatory myopathies, highlights the common pitfalls and mistakes in therapy, and identifies the emerging new therapies. In uncontrolled studies, PM and DM respond to prednisone to some degree and for some period of time, while a combination with one immu-nosuppressive drug (azathioprine, cyclosporine, mycophenolate, methotrexate) offers additional benefit or steroid-sparing effect. In contrast, IBM is resistant to most of these therapies, most of the time. Controlled studies have shown that IVIg is effective and safe for the treatment of DM, where is used as a second, and at times first, line therapy. IVIg seems to be also effective in the majority of patients with PM based on uncontrolled series, but it offers transient help to a small number of patients with IBM especially those with dysphagia. Bona fide patients with PM and DM who become resistant to the aforementioned therapies, may respond to rituximab, tacrolimus or rarely to an tumor necrosis factor alpha inhibitor. For IBM patients, experience with alemtuzumab, a T-cell-depleting monoclonal antibody, is encouraging.

  3. Clinical trials in CIDP and chronic autoimmune demyelinating polyneuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2012-05-01

    The main chronic autoimmune neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy. On the basis of randomized controlled studies, corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis provide short-term benefits in CIDP. MMN responds only to IVIg. Because in MMN and CIDP, IVIg infusions are required every 3-6 weeks to sustain benefits or long-term remissions, there is a need for "IVIg-sparing" agents. In CIDP, immunosuppressive drugs, such as azathioprine, cyclosporine, methotrexate, mycophenolate, and cyclophosphamide, are used, but controlled trials have not shown that they are effective. Controlled trials have also not shown benefit to any agents in anti-MAG neuropathy. However, clinicians use many immunosuppressive drugs in both settings, but all have potentially serious side effects and are only effective in some patients. Thus, there is a need for new therapies in the inflammatory and paraproteinemic neuropathies. New agents targeting T cells, B cells, and transmigration and transduction molecules are discussed as potential treatment options for new trials. The need for biomarkers that predict therapeutic responses or identify patients with active disease is emphasized, and the search for better scoring tools that capture meaningful changes after response to therapies is highlighted.

  4. Current treatment of the inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1994-11-01

    Among the main concerns regarding the current therapy for the inflammatory myopathies are a lack of adequate controlled trials, a lack of objective means to reliably measure muscle strength, lack of natural history data, consideration of polymyositis, dermatomyositis, and inclusion-body myositis as a homogeneous group of inflammatory myopathies, and reliance on nonspecific markers for determining prognosis and assessing response to therapies. Prednisone remains the drug of choice in treating these disorders, although a controlled trial has never been undertaken to study its efficacy. Among the steroid-sparing agents, azathioprine, methotrexate, cyclosporine, and chlorambucil are used with invariably low to moderate success. There are no results of controlled trials to indicate whether one of these drugs is superior to another. Intravenous immunoglobulin, which is very expensive, was shown in a controlled trial to be effective in steroid-resistant dermatomyositis not only in dramatically improving muscle strength and skin rash but also in resolving the underlying immunopathology. Controlled trials of intravenous immunoglobulin in patients with polymyositis and inclusion-body myositis are under way. Inclusion-body myositis has emerged as a common inflammatory myopathy that is predictably disabling and resistant to most therapies.

  5. 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.

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Prurigo: diagnosis and management.

    Science.gov (United States)

    Wallengren, Joanna

    2004-01-01

    Prurigo is a condition of nodular cutaneous lesions that itch (pruire) intensely. Although the acute form can be caused by insect stings, most of the subacute and chronic forms appear to be idiopathic. Toxic agents deposited in the skin by exogenous factors such as parasites, bacteria, or topically or orally administered drugs can induce itch. In susceptible individuals, physical mechanisms such as UV light can induce changes in epidermal innervation that result both in itch generally and in prurigo lesions. Prurigo is sometimes associated with atopy, pregnancy, internal diseases, malabsorption, or malignancy. Some forms of prurigo may be secondary to scratching. Emotional factors can also influence the perception of itch and induce prurigo by provoking scratching. These are the various specialized forms of prurigo, and there are certain others, such as prurigo pigmentosa, that have some ethnic preference. Topical treatments by corticosteroids, coal tar, bath photochemotherapy, UVB, cryotherapy, or capsaicin, as well as systemic regimens involving use of psoralen + UVA (PUVA), erythromycin, arotinoid acid, cyclosporine, chloroquine, dapsone, minocycline, naltrexone, azathioprine or thalidomide are used for the treatment of this condition. Psychotherapeutic agents to treat problems of mood that deteriorate prurigo are also prescribed. Combined sequential treatments for generalized, therapy-resistant cases need to be tailored to the exacerbations that occur and to provide maintenance treatment in order to enable the patient to withstand the intolerable itch. PMID:15109273

  10. The effect of somatostatin 201-995 on the early course of porcine pancreaticoduodenal allotransplantation.

    Science.gov (United States)

    Nicholson, C P; Barr, D; Oeltjen, M R; Munn, S R; DiMagno, E P; Carpenter, H A; Sarr, M G; Perkins, J D

    1991-01-01

    This study was undertaken to determine the effects of somatostatin 201-995 (SMS) on the maintenance dose of intravenous cyclosporine and on graft blood flow, exocrine secretion, and rejection after porcine pancreaticoduodenal allotransplantation (PDA). For seven days, 12 pigs (6 control, 6 SMS-treated) were studied to determine the effects of SMS on serum CsA concentrations. Twenty-six pigs (14 control, 12 SMS) with streptozocin-induced diabetes underwent PDA. Blood flow was measured through graft celiac and superior mesenteric arteries 15 and 60 min after reperfusion. SMS (75 micrograms s.c.) was given after the 15-min blood-flow measurement in the SMS group. Sixteen pigs (8 control, 8 SMS) were followed postoperatively with daily measurements of serum glucose and amylase concentrations, and urine amylase and trypsin activities. All pigs were immunosuppressed with azathioprine, prednisone, and i.v. CsA. SMS pigs also received SMS (75 micrograms s.c.) every 8 hr. SMS had no effect on maintenance dose of CsA or on serum amylase, urine amylase, or urine trypsin activities. Mean days to rejection were also not affected. Intraoperative graft blood flow was significantly decreased by SMS, but incidence of graft thrombosis was unchanged. These results suggest that in the porcine PDA model, SMS does not appear to inhibit exocrine secretion and potentially may adversely affect the early course of PDA by decreasing graft blood flow. PMID:1670973

  11. Interstitial lung disease in systemic sclerosis: where do we stand?

    Directory of Open Access Journals (Sweden)

    Susanna Cappelli

    2015-09-01

    Full Text Available Interstitial lung disease (ILD is common in systemic sclerosis (SSc patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease. Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described. Nonselective immunosuppressors are still the main treatment for ILD, with cyclophosphamide (CYC most widely used to obtain remission. Novel therapies towards specific molecular and cellular targets have been suggested; in particular, rituximab (RTX has shown promising results, but further research is needed. It is of paramount importance to define the severity of the disease and the risk of progression in order to define the need for treatment and the treatment intensity. We propose the division of the treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation, medium intensity (CYC and RTX and low intensity (azathioprine (AZA and mycophenolate mofetil (MMF. After obtaining remission, maintenance treatment with AZA or MMF should be started. In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD.

  12. Pulmonary Langerhans Histiocytosis: an uncommon cause of interstitial pneumonia in a patient with Sjögren syndrome.

    Science.gov (United States)

    González García, Andrés; Callejas Rubio, José Luis; Ríos Fernández, Raquel; Ortego Centeno, Norberto

    2016-03-01

    Sjögren syndrome is a chronic, systemic, and autoimmune disorder that targets exocrine glands by remarkable B cell hyperactivity. Eventually, it is associated with extra-glandular clinical manifestations that affect essentially any organ system, including pulmonary involvement. Interstitial lung disease is one of the most serious pulmonary complications, and the early diagnosis is essential to initiate a prompt therapy. On the other hand, Sjögren syndrome could present concomitantly with several rheumatologic diseases such as systemic lupus erythematosus or rheumatoid arthritis. Pulmonary Langerhans Histiocytosis is a rare clonal proliferative disease characterized by pulmonary involvement by cells phenotypically similar to Langerhans cells. We describe the case of a nonsmoker 62-year-old woman with Sjögren syndrome who presented concomitantly a Pulmonary Langerhans Histiocytosis mimicking a pulmonary complication of its Sjögren. Fortunately, she had a well response to corticosteroids and azathioprine regimen. The aim of the paper is to emphasize the importance of the good differential diagnosis related to the pulmonary involvement. To the best of our knowledge, this is the first description of these two entities in the literature. PMID:25894436

  13. 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.

  14. 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.

  15. Thiopurines in the Management of Crohn’s Disease: Safety and Efficacy Profile in Patients with Normal TPMT Activity—A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Amine Benmassaoud

    2016-01-01

    Full Text Available Background and Aims. Thiopurines are used in the treatment of Crohn’s disease (CD and thiopurine S-methyltransferase (TPMT activity can guide thiopurine dosing to avoid adverse events. This retrospective study evaluated the safety and efficacy of starting thiopurines at low dose versus full dose in patients with CD and normal TPMT. Methods. This was a single center retrospective study including adult CD patients with normal TPMT levels (≥25 nmol/hr/g Hgb who were followed for 1 year. Patients started at full dose of azathioprine (2–2.5 mg/kg or 6-mercaptopurine (1–1.5 mg/kg were compared to patients started at low dose. Harvey-Bradshaw index, treatment failure, and drug-related adverse events were recorded. Results. Our study included 134 patients. Both groups had similar incidences of drug-related adverse events and discontinuation of therapy due to side effects. Fifty-six percent of all adverse events occurred within 31 days and 92% occurred within 3 months of therapy. Clinical response favored the full-dose group at 6 months (69% versus 27%, p=0.0542. Conclusions. Our study indicates that it is safe to start patients on full-dose thiopurine when they have a normal TPMT given its very similar toxicity profile to patients started on low dose. This may also positively impact efficacy.

  16. Clinical characteristics and response to therapy of autoimmune hepatitis in an urban Latino population

    Science.gov (United States)

    Zahiruddin, Ayesha; Farahmand, Abtin; Gaglio, Paul; Massoumi, Hatef

    2016-01-01

    Aim: We hypothesized that AIH outcomes might be different in our patient population that consists of a large number of Latinos. Background: Literature has suggested that the presentation and outcome of autoimmune hepatitis can be different among different ethnicity and communities. Patients and methods: We performed a retrospective chart review of Latino patients with AIH diagnosed between 2002-2012. Complete and partial remissions were defined as normalization of liver enzyme values, or achieving less than twice the upper limit normal (ULN), respectively. Results: A total of 28 patients were identified. 26 (93%) were female. 13 (46%) had an acute presentation, one with type 2 AIH and 3 with ANA seronegative disease. The average pathologic stage (Ishak score) was 3.44±1.67 (range: 0-6). Complete and partial remission was achieved in 20 (71%) and 5 (18%) patients respectively. Ten patients (38%) required maintenance prednisone either alone (2), or in combination with Azathioprine (6) or Mycophenolate Mofetil (2). Remission in the majority of patients, including 14 (50%) who were cirrhotic. Six of 14 (43%) cirrhotic patients were asymptomatic at the time of diagnosis. Conclusion: In an urban Latino population, cirrhosis was the initial presentation of AIH in a significant percentage of patients raising concerns regarding insufficient screening for AIH in this patient population. A large number of patients required continuous prednisone to avoid relapse. PMID:27458516

  17. Oxidative damage to RPA limits the nucleotide excision repair capacity of human cells

    Science.gov (United States)

    Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

    2015-01-01

    Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin, interact with UVA radiation to generate reactive oxygen species (ROS) that diminish NER capacity by causing protein damage. The RPA DNA binding protein plays a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself is likely to be an important contributor to skin cancer risk. PMID:26134950

  18. 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.

  19. Management of difficult inflammatory bowel disease: where are we now?

    Institute of Scientific and Technical Information of China (English)

    D.S. Rampton

    2000-01-01

    Management of inflammatory bowel disease includes not only drug, endoscopic and surgical therapy but alsopsychosocial support, dietary and specific nutritional measures: a multidisciplinary medical, surgical, nursingand dietetic approach is essential for all patients, particularly those with complex or refractory disease. Inthis paper, current treatment of acute severe ulcerative colitis and steroid-refractory or -dependent Crohn'sdisease is reviewed. Adjunctive intravenous cyclosporin is an alternative to urgent colectomy in steroid-refractory patients with acute severe ulcerative colitis, while the place of intravenous heparin for thisindication awaits clarification. Azathioprine or 6-mercaptopurine are useful options in chronically active,steroid-refractory or -dependent Crohn's disease, but may take up to 4 months to work. Methotrexate is amore recent immunomodulatory alternative. Of new therapies selectively aimed at specific pathophysiologicaltargets, the first to reach clinical application is anti-TNF-alpha antibody (infliximab) for refractory Crohn'sdisease: its benefits are promising, but experience with it is limited to date, its cost is high and there areuncertainties about long-term safety. In view of the increasing variety and complexity of management optionsin inflammatory bowel disease, whether apparently responsive or difficult to treat, patients must participatein decisions about which therapies they are to be given.

  20. Treatment of inflammatory bowel disease: A review of medical therapy

    Institute of Scientific and Technical Information of China (English)

    Patricia L Kozuch; Stephen B Hanauer

    2008-01-01

    Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; nonsystemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-rnederate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

  1. Are we giving biologics too late? The case for early versus late use

    Institute of Scientific and Technical Information of China (English)

    Elena Ricart; Orlando García-Bosch; Ingdd Ordás; Julián Panés

    2008-01-01

    Corticosteroids and immunomodulators have been the mainstay therapies for Crohn's disease. Corticosteroids are highly effective to control symptoms in the shortterm, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn's disease. In the last decade, medical therapy for Crohn's disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn's disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn's disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn's disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn's disease remain still unanswered.

  2. Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

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    Bipul Nath

    2013-01-01

    Full Text Available The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed , prolonged absorption time, decreased , and absorption rate constant (Ka, indicating a reduced systemic toxicity of the drug as compared to other dosage forms.

  3. Implementation of Clinical Pharmacogenomics within a Large Health System: From Electronic Health Record Decision Support to Consultation Services.

    Science.gov (United States)

    Hicks, J Kevin; Stowe, David; Willner, Marc A; Wai, Maya; Daly, Thomas; Gordon, Steven M; Lashner, Bret A; Parikh, Sumit; White, Robert; Teng, Kathryn; Moss, Timothy; Erwin, Angelika; Chalmers, Jeffrey; Eng, Charis; Knoer, Scott

    2016-08-01

    The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics. We describe the development of pharmacist-managed pharmacogenomic services within a large health system. The Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B*57:01-abacavir, HLA-B*15:02-carbamazepine, and TPMT-thiopurines (i.e., azathioprine, mercaptopurine, and thioguanine) were systematically integrated into patient care. Sixty-three custom rules and alerts (20 for TPMT-thiopurines, 8 for HLA-B*57:01-abacavir, and 35 for HLA-B*15:02-anticonvulsants) were developed and deployed to the EHR for the purpose of providing point-of-care pharmacogenomic decision support. In addition, a pharmacist and physician-geneticist collaboration established a pharmacogenomics ambulatory clinic. This clinic provides genetic testing when warranted, result interpretation along with pharmacotherapy recommendations, and patient education. Our processes for developing these pharmacogenomic services and solutions for addressing implementation barriers are presented. PMID:27312955

  4. The effects of immune modulation on plutonium dioxide lung carcinogenesis in the rat

    International Nuclear Information System (INIS)

    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 PuO2 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

  5. Challenges for lupus management in emerging countries.

    Science.gov (United States)

    Tazi Mezalek, Zoubida; Bono, Wafaa

    2014-06-01

    In emerging countries, systemic lupus erythematosus (SLE) has been associated with several unfavorable outcomes including disease activity, damage accrual, work disability and mortality. Poor socioeconomic status (SES) and lack of access to healthcare, especially in medically underserved communities, may be responsible for many of the observed disparities. Diagnostic delay of SLE or for severe organ damages (renal involvement) have a negative impact on those adverse outcomes in lupus patients who either belong to minority groups or live in emerging countries. Longitudinal and observational prospective studies and registries may help to identify the factors that influence poor SLE outcomes in emerging countries. Infection is an important cause of mortality and morbidity in SLE, particularly in low SES patients and tuberculosis appears to be frequent in SLE patients living in endemic areas (mainly emerging countries). Thus, tuberculosis screening should be systematically performed and prophylaxis discussed for patients from these areas. SLE treatment in the developing world is restricted by the availability and cost of some immunosuppressive drugs. Moreover, poor adherence has been associated to bad outcomes in lupus patients with a higher risk of flares, morbidity, hospitalization, and poor renal prognosis. Low education and the lack of money are identified as the main barrier to improve lupus prognosis. Newer therapeutic agents and new protocols had contributed to improve survival in SLE. The use of corticoid-sparing agents (hydroxychloroquine, methotrexate, azathioprine and mycophenolate mofetif) is one of the most useful strategy; availability of inexpensive generics may help to optimize access to these medications.

  6. Managing new-onset gout in pediatric renal transplant recipients: when, how, to what extent.

    Science.gov (United States)

    Assadi, Farahnak

    2013-01-01

    Hyperuricemia and gout are common among adult renal transplant recipients, but it is rarely reported following pediatric renal transplantations. Treating gout in pediatric kidney transplant recipients presents clinical challenges to the management of both immunosuppressive regimen and hyperuricemia for their effects on serum uric acid levels, renal function and drug interactions. Most renal transplant recipients have a relative impairment of renal clearance of urate due to abnormalities in renal transport, explaining the association of hyperuricemia and decreased glomerular filtration rate. Risk factors for the development of gout include impaired renal function, hypertension, heart failure and diabetes mellitus. Calcineurin inhibitors, particularly cyclosporine, are the most important risk factor for gout in transplant recipients and should not be used in pediatric renal transplant recipients. Diuretic therapy increases the risk of gout by causing extracellular volume contraction with consequent enhancement of proximal tubular reabsorption. Corticosteroids are increasingly replacing nonsteroidal antiinflammatory drugs and colchicine for the treatment of acute gout flares because they have little effect on kidney function. Proper management is aimed at lowering serum uric acid level below 6.0 mg/dL with xanthine oxidase inhibitors such as allopurinol or febuxostat. Allopurinol and mycophenolate mofetil are safer to use in combination than are allopurinol and azathioprine. Febuxostat is an alternative to allopurinol in patients with allopurinol intolerance or hypersensitivity. Pegloticase is indicated for patients with severe gout in whom allopurinol and febuxostat have not been effective or tolerated. PMID:22941874

  7. Antiepileptic drug hypersensitivity syndrome.

    Science.gov (United States)

    Schlienger, R G; Shear, N H

    1998-01-01

    The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS 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 incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%. PMID:9798755

  8. Use of allopurinol to optimize thiopurine immunomodulator efficacy in inflammatory bowel disease.

    Science.gov (United States)

    Sparrow, Miles P

    2008-07-01

    The thiopurine immunomodulators azathioprine and 6-mercaptopurine are integral to the management of inflammatory bowel disease (IBD), particularly as corticosteroid-sparing and maintenance agents; however, up to 50% of patients do not adequately respond to these agents. Advances in pharmacogenomics and an increased understanding of thiopurine metabolism have led to the practice of measuring the thiopurine metabolites 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP) to help achieve optimal immunomodulator dosages. Metabolite profiles are also useful for categorizing the reasons for thiopurine treatment failures. A desirable metabolite profile favors 6-TGN production over 6-MMP formation; however, a significant subgroup of IBD patients, perhaps 15%, preferentially metabolizes thiopurines toward the inefficacious and potentially hepatotoxic metabolite 6-MMP. The xanthine oxidase inhibitor allopurinol has been shown recently to advantageously switch thiopurine metabolism toward 6-TGN production in this subgroup of patients, and small studies have shown this switch to be safe and clinically beneficial. This article reviews evidence describing the use of allopurinol to optimize immunomodulator metabolism, provides careful practice guidelines to clinicians considering this strategy, and briefly discusses the potential mechanisms by which this favorable interaction occurs. PMID:21960930

  9. Drug hypersensitivity syndrome.

    Science.gov (United States)

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    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. PMID:21220873

  10. Gout and organ transplantation.

    Science.gov (United States)

    Stamp, Lisa K; Chapman, Peter T

    2012-04-01

    Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use. PMID:22258500

  11. Oxidation-mediated DNA cross-linking contributes to the toxicity of 6-thioguanine in human cells.

    Science.gov (United States)

    Brem, Reto; Karran, Peter

    2012-09-15

    The thiopurines azathioprine and 6-mercaptopurine have been extensively prescribed as immunosuppressant and anticancer agents for several decades. A third member of the thiopurine family, 6-thioguanine (6-TG), has been used less widely. Although known to be partly dependent on DNA mismatch repair (MMR), the cytotoxicity of 6-TG remains incompletely understood. Here, we describe a novel MMR-independent pathway of 6-TG toxicity. Cell killing depended on two properties of 6-TG: its incorporation into DNA and its ability to act as a source of reactive oxygen species (ROS). ROS targeted DNA 6-TG to generate potentially lethal replication-arresting DNA lesions including interstrand cross-links. These triggered processing by the Fanconi anemia and homologous recombination DNA repair pathways. Allopurinol protected against 6-TG toxicity by acting as a ROS scavenger and preventing DNA damage. Together, our findings provide mechanistic evidence to support the proposed use of thiopurines to treat HR-defective tumors and for the coadministration of 6-TG and allopurinol as an immunomodulation strategy in inflammatory disorders. PMID:22822082

  12. Two brothers with skewed thiopurine metabolism in ulcerative colitis treated successfully with allopurinol and mercaptopurine dose reduction.

    Science.gov (United States)

    Hoentjen, Frank; Hanauer, Stephen B; de Boer, Nanne K; Rubin, David T

    2012-01-01

    Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP and low 6-TGN levels, despite normal TMPT enzyme activity, accompanied by transaminitis. Allopurinol was introduced in combination with MP dose reduction. For both brothers addition of allopurinol was associated with successful remission and optimized MP metabolites. These siblings with active UC illustrate that skewed thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead to adverse events in the absence of disease control. We confirm previous data showing that addition of allopurinol can reverse this skewed metabolism, and reduce both hepatotoxicity and disease activity, but we now also introduce the concept of a family history of preferential MP metabolism as a clue to effective management for other family members. PMID:22147254

  13. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    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.

  14. Urate-oxidase for the treatment of tophaceous gout in heart transplant recipients. A report of three cases.

    Science.gov (United States)

    Rozenberg, S; Roche, B; Dorent, R; Koeger, A C; Borget, C; Wrona, N; Bourgeois, P

    1995-05-01

    Gout in heart transplant recipients is common and poses a significant therapeutic challenge. Concomitant administration of azathioprine and allopurinol therapy carries a high risk of leukopenia. Uricosuric agents can cause renal lithiasis and/or acute renal failure in patients with renal failure and/or high urinary levels of uric acid. We report our experience with urate-oxidase in three heart transplant recipients with severe polyarticular and tophaceous gout, a history of leukopenia under allopurinol and unresponsiveness or contraindications to uricosuric agents. Urate-oxidase was given parenterally in a dosage of 1000 units per day, seven days a month. The injections were done intramuscularly in one patient and intravenously in the other two, who were under anticoagulant therapy. Patients 1 and 2 received 12 and 6 courses, respectively. The third patient had had four courses and was still under treatment at the time of this writing. Shrinking of the tophi and improved mobility of the fingers were seen in all three patients after the second course. No adverse effects were recorded. Our experience suggests that urate-oxidase therapy may decrease the urate burden in patients with severe tophaceous gout. Urate-oxidase therapy should be viewed as a phase in the treatment of gout, which must be followed by administration of another agent. PMID:7655872

  15. Advances in the treatment of cutaneous lupus erythematosus.

    Science.gov (United States)

    Kuhn, A; Landmann, A; Wenzel, J

    2016-07-01

    Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE.

  16. 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.

  17. National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection.

    Science.gov (United States)

    Axelrod, D A; Naik, A S; Schnitzler, M A; Segev, D L; Dharnidharka, V R; Brennan, D C; Bae, S; Chen, J; Massie, A; Lentine, K L

    2016-08-01

    Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics. PMID:26901466

  18. Heart transplantation in neonates and children. Intermediate-term results

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    Estela Azeka

    2000-03-01

    Full Text Available OBJECTIVE: To assess intermediate-term outcome in children who have undergone orthotopic heart transplantation. METHODS: We carried out a longitudinal and prospective study between October '92 and June '99 comprising 20 patients with ages ranging from 12 days to 7 years (mean of 2.8 years. We employed a double immunosuppression protocol with cyclosporine and azathioprine and induction therapy with polyclonal antithymocyte serum. Survival and complications resulting from the immunosuppression protocol were analyzed. RESULTS:The double immunosuppression protocol and the induction therapy with polyclonal antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1 and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient died due to acute rejection 40 days after transplantation; another patient died 2 years after transplantation due to lymphoproliferative disorder; a third patient died because of primary failure of the graft; and a fourth patient died due to bronchopneumonia. The major complications were as follows: acute rejection, infection, nephrotoxicity, and systemic hypertension. The means of rejection and infection episodes per patient were 2.9 and 3.4, respectively. After one year of transplantation, a slight reduction in the creatinine clearance and systemic hypertension were observed in 7 (38.9% patients. CONCLUSION: Heart transplantation made life possible for those patients with complex congenital heart diseases and cardiomyopathies in refractory congestive heart failure constituting a therapeutical option for this group of patients in the terminal phase.

  19. 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

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

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    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.

  1. 炎症性肠病联合治疗中的药物相互作用

    Institute of Scientific and Technical Information of China (English)

    武丽娜; 张波; 鲁重美

    2015-01-01

    Polypharmacy is an increasing concern in the management of inflammatory bowel disease.This review describes drug interactions in the combination therapy of inflammatory bowel disease,including aminosalicylate ,corticosteroid,azathioprine,methotrexate,cyclosporine,thalidomide,cyclophosphamide and antibiotics,TNF inhibitor.%氨基水杨酸制剂、肾上腺糖皮质激素、硫唑嘌呤、甲氨蝶呤、环孢素、沙利度胺、环磷酰胺、抗肿瘤坏死因子α单克隆抗体等药物在炎症性肠病(Inflammatory bowel dis-ease,IBD)治疗应用较广。目前多种药物联合应用在 IBD 治疗中越来越常见,药物之间的相互作用也日益受到医学界的重视。现介绍 IBD 治疗中常见的药物联用对彼此血药浓度、毒副作用、治疗效果等的影响。

  2. Conventional therapy for Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Carsten Büning; Herbert Lochs

    2006-01-01

    Crohn's disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the pathophysiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a useful tool for clinicians in the challenging treatment of CD.

  3. Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert; María Chaparro; Fernando Gomollón

    2011-01-01

    Misconceptions are common in the care of patients with inflammatory bowel disease (IBD). In this paper, we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines, to review the related scientific evidence, and make appropriate recommendations. Prevention of errors needs knowledge to avoid making such errors through ignorance. However, the amount of knowledge is increasing so quickly that one new danger is an overabundance of information. IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems. With regard to the use of 5-aminosalicylates, the best practice may to be consider abandoning the use of these drugs in patients with small bowel Crohn' s disease. The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis; once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy. With regard to thiopurines, they seem to be as effective in ulcerative colitis as in Crohn' s disease. Underdosing of thiopurines is a form of undertreatment. Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse. Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine. Finally, thiopurine methyltransferase (TPMT) screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.

  4. Budesonide induces complete remission in autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Antal Csepregi; Christoph R(o)cken; Gerhard Treiber; Peter Malfertheiner

    2006-01-01

    AIM: Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis (AIH). However, only 65% of the patients enter complete histological remission. Recently, budesonide (BUD) was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH.METHODS: Eighteen patients (12 women, 6 men; mean age 45.4±21 years) with AIH were treated with BUD (Budenofalk(R)) 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis (n = 5) or primary sclerosing cholangitis (n = 2). Advanced liver fibrosis or cirrhosis was present in 6 patients.RESULTS: Fifteen (83%) patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis, were given BUD as first-line therapy, of which seven enter remission. Three patients,two with liver cirrhosis, did not improve. All patients with second-line therapy experienced long-term remission.A histological remission was also seen in three patients.Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis (n = 4).CONCLUSION: BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

  5. Efficacy of extracranial-intracranial bypass for progressive middle cerebral artery occlusion associated with active Sjögren's syndrome: case report.

    Science.gov (United States)

    Sakata, Hiroyuki; Fujimura, Miki; Sato, Kenichi; Shimizu, Hiroaki; Tominaga, Teiji

    2014-09-01

    Sjögren syndrome affecting the major cerebral arteries is rare, and an optimal therapeutic strategy to counteract such a lesion has not yet been established. We herein report a case of a 39-year-old woman with a history of primary Sjögren syndrome, which had previously been treated with immunosuppressive therapy, manifesting with a crescendo transient ischemic attack because of left middle cerebral artery stenosis. Despite the administration of high doses of prednisolone and azathioprine for active Sjögren syndrome, the frequency of crescendo transient ischemic attacks increased with the progression of stenosis and magnetic resonance imaging showed the development of subacute cerebral infarction. Single-photon emission computed tomography with N-isopropyl[(123)I]-p-iodoamphetamine revealed apparent hemodynamic compromise in the affected cerebral hemisphere. In light of the increased risk of further progression of cerebral infarction, we decided to perform surgical revascularization in spite of her active inflammatory condition. The patient underwent extracranial-intracranial bypass without complications and was treated with intensive immunosuppressive therapy during the perioperative period. Based on our findings, we recommend surgical revascularization for occlusive cerebrovascular disease with hemodynamic compromise in combination with intensive immunosuppressive therapy, even in the active inflammatory state of autoimmune diseases, if ischemic symptoms are medically uncontrollable.

  6. [Association between ulcerative colitis and primary esclerosing cholangitis].

    Science.gov (United States)

    Aguilar Sanchez, Victor; Guzman Rojas, Patricia; Bravo Paredes, Eduar; Rios Perez, Cristian

    2016-01-01

    Ulcerative Colitis (UC) is associated to Primary Sclerosing Cholangitis (PSC) in 80% of cases, and this association is more common than the one with Crohn’s disease. Nevertheless, the prevalence of PSC in patients with UC is only 2.9% in Latin America. We present the case of a female patient who presents a clinical history characterized for chronic diarrhea of one year of evolution, associated to fever, oral ulcers and loss of weight. In the laboratory results there is an elevation in the following: alkaline phosphatase, GGT, ALT and AST, for that reason we decide to do an abdominal ultrasound finding a hepatomegaly. In the colonoscopy we found an ulcerative colitis. Later, we do a magnetic resonance cholangiopancreatography, because of the diagnosis of UC and the abnormalities at the liver function tests, diagnosing PSC associated to UC. At that moment, the patient starts treatment with sulfasalazine that is stopped because of an adverse effect, starting prednisone and azathioprine. The patient then is discharged with the medication already mentioned and has a favorable clinical outcome. We decide to report the case because is the second reported case in Peru, being this association not commonly found in the South hemispheric. PMID:27409097

  7. 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.

  8. Successful Renal Transplantation in a Patient with Behcet Disease and Hodgkin Lymphoma in Remission

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    Vural Taner YILMAZ

    2011-05-01

    Full Text Available Behcet's disease (BD is an inflammatory multisystemic disease characterized by perivascular inflammation and generally presents with recurrent oral and genital ulcers and uveitis. It is known that BD may also involve the kidneys. Amyloidosis, glomerulonephritis (crescentic, proliferative, IgA nephropathy, interstitial nephritis are commonly described renal lesions which may lead to end-stage renal disease (ESRD in BD. Immunosuppressive therapies used for the treatment of BD may cause malignant diseases (lymphoma, skin and solid organ malignancies, etc. The risk with azathioprin is especially high after 10 years of treatment. Cyclosporine, another immunosuppressive agent frequently used for treatment of BD, also has tumorigenic potential and is associated with renal toxicity and renal failure. Renal transplantation may be performed in patients with malignancies after a 2-5 year complete remission period, although it may differ according to the type of tumor. We report a case of end-stage renal disease and Hodgkin's lymphoma occurring after treatment with immunosuppressive medicine for BD. The patient was successfully treated with renal transplantation.

  9. Effect of Anapsos® in a murine model of experimental trichomoniasis

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    Nogal-Ruiz J.J.

    2003-12-01

    Full Text Available Immunomodulator effect of Anapsos® (Polypodium leucotomos extract in NMRI (US Naval Medical Research Institute outbred mice infected by the intraperitoneal route with 107 Trichomonas vaginalis has been tested. Gross histopathologic changes in abdominal organs and mortality rate, as a consequence of the pathogenicity of the protozoa and the immune response of the host, were evaluated. Among the different treatment regimes assayed, Anapsos® at doses of 20 mg/Kg/day administered for 10 days before infection decreases the parasite pathogenicity index (PI in the treated animals when compared to those of the untreated control group. The immunosuppresor treatments with azathioprine (100 mg/Kg/day x 1, cyclophosphamide (100 mg/Kg/day x 1, and FK-506 (10 mg/Kg/day x 10 significantly decreased the PI, while an immunostimulant treatment with glycophosphopeptical (13 mg/Kg/day x 10 increased it. These assays have shown the usefulness of the murine model of experimental trichomoniasis for the study of immunomodulator activity of natural or synthetic drugs.

  10. 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.

  11. A case of exorbitism in association with Wegener's granulomatosis with renal involvement.

    Science.gov (United States)

    Beji, S; Fatma, L Ben; Chebbi, A; Rais, L; Krid, M; Smaoui, W; Maiz, H Ben; Zouaghi, K; Moussa, F Ben

    2012-03-01

    Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis involving 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 glomerulonephritis. 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 bilateral exophthalmos. Prompt recognition of this early manifestation is important for the institution of early treatment. PMID:22382229

  12. Atypical Mycobacterial Infection Presenting as Persistent Skin Lesion in a Patient with Ulcerative Colitis

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    Giorgos Bamias

    2011-01-01

    Full Text Available Immunosuppressive drugs are commonly used for the treatment of inflammatory bowel disease. Patients receiving immunosuppressants are susceptible to a variety of infections with opportunistic pathogens. We present a case of skin infection with Mycobacterium chelonae in a 60-year-old Caucasian woman with ulcerative colitis who had been treated with corticosteroids and azathioprine. The disease manifested with fever and rash involving the right leg. Infliximab was administered due to a presumptive diagnosis of pyoderma gangrenosum, leading to worsening of the clinical syndrome and admission to our hospital. Routine cultures from various sites were all negative. However, Ziehl-Neelsen staining of pus from the lesions revealed acid-fast bacilli, and culture yielded a rapidly growing mycobacterium further identified as M. chelonae. The patient responded to a clarithromycin-based regimen. Clinicians should be aware of skin lesions caused by atypical mycobacteria in immunocompromised patients with inflammatory bowel disease. Furthermore, they should be able to thoroughly investigate and promptly treat these conditions.

  13. Macular serpiginous choroiditis

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    Sahu Dinesh

    2002-01-01

    Full Text Available Purpose: To report a variant form of serpiginous choroiditis, that initially or predominantly involved the macular area. Methods: Nine eyes of 6 patients with the macular form of serpiginous choroiditis were evaluated clinically and angiographically in a longitudinal fashion for a period of 12-36 months. The active stage and the recurrences were treated by oral and periocular cortico steroids; and two patients were supplemented with oral azathioprine. Most of these patients were referred to our center with varied diagnoses. Results: In this group, 4 were male and 2 were female with an average age of 30.5 years. Three patients had bilateral macular lesions, two had typical serpiginous choroiditis in the fellow eye and the remaining one had unilateral macular involvement alone. The initial visual acuity was 6/60 or less in 60% eyes whereas the final visual acuity was 6/18 or better in 66% eyes. Angiographic findings were typical of serpiginous choroiditis characterised by early hypofluorescence followed by leakage and staining of the borders and the lesion itself without any evidence of choroidal ischaemia or retinal vascular abnormalities. Conclusion: The macular variant of serpiginous choroiditis can mimic many other macular pathologic lesions, thus posing a diagnostic dilemma. Because of its relentless destructive course, early diagnosis and prompt treatment is required to prevent sight-threatening complications.

  14. Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Neurosarkoidose

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    Holzapfel R

    2011-01-01

    Full Text Available Die Neurosarkoidose ist eine seltene Komplikation der Sarkoidose und wird mit einer Prävalenz von 5–15 % beschrieben. Ihr klinisches Bild ist sehr variabel und oft Folge einer aseptischen granulomatösen Meningitis. Diese führt häufig zu Hirnnervenaffektionen oder einer aseptischen Meningitis mit Liquorzirkulationsstörungen. Auch intraparenchymatöse Granulome kommen vor, häufig mit Befall basaler mittelliniennaher Strukturen wie Hypothalamus und Hypophyse, die zu einer Enzephalopathie führen können. Das MRT besitzt einen hohen diagnostischen Stellenwert, die Befunde sind allerdings nicht spezifisch und können sehr variabel sein. Daher bleibt der histologische Granulomnachweis Goldstandard für die Diagnose einer Neurosarkoidose, was aber nur bei wenigen Patienten möglich ist. Laboruntersuchungen sind wenig sensitiv und spezifisch, was die Neurosarkoidose zu einer diagnostischen Herausforderung macht, insbesondere wenn Zeichen einer systemischen Sarkoidose fehlen. Angesichts der erheblichen Morbidität der Erkrankung sollte eine frühe und konsequente Behandlung erfolgen. Dies geschieht in der Regel mit Kortikosteroiden, unterstützt durch Immunsuppressiva wie Azathioprin oder Methotrexat.

  17. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.

    Science.gov (United States)

    Götestam Skorpen, Carina; Hoeltzenbein, Maria; Tincani, Angela; Fischer-Betz, Rebecca; Elefant, Elisabeth; Chambers, Christina; da Silva, Josè; Nelson-Piercy, Catherine; Cetin, Irene; Costedoat-Chalumeau, Nathalie; Dolhain, Radboud; Förger, Frauke; Khamashta, Munther; Ruiz-Irastorza, Guillermo; Zink, Angela; Vencovsky, Jiri; Cutolo, Maurizio; Caeyers, Nele; Zumbühl, Claudia; Østensen, Monika

    2016-05-01

    A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease.

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

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    Field, E.H.; Strober, S.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.L.; Tanay, A.S.; Calin, H.J.; Terrell, C.P.; Kaplan, H.S.

    1983-08-01

    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.

  19. Plasma exchange in progressive systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Mohammad Bagher Owlia

    2015-10-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune systemic disease of unknown etiology. Present treatment modalities have limited impact on clinical/ laboratory outcomes. For the first time in our center, we used plasma exchange (PEx in a rather young woman with recent onset but progressive SSc. She is a 39-year-old woman with a recent history of skin stiffness, Raynaud’s phenomenon, nail fold capillary changes and newly diagnosis of SSc presented to us due to worsening her clinical symptoms even after initiation of routine remedies such as low dose oral prednisolone, Ca-channel blockers, azathioprine and pentoxyfylline. After obtaining written consent, interdisciplinary discussion with experts in this field and agreement we started a series of plasma exchange with FFP replacement for her. A dramatic clinical response was observed in respect to Raynaud’s phenomenon, skin stiffness, tendon rub after three sessions of PEx. Her modified Rodnan skin score (MRSS dropped from 36 (before commencement of therapy to 28 in day 4 and 18 in day 20 after 15 sessions of PEx. In conclusion PEx could significantly modify the course of SSc as observed in our case study. Elimination of culprit immune mediators/cytokines/autoantibodies could be the possible mechanism of action of PEx. 

  20. Drugs in induction and treatment of idiopathic inflammatory myopathies.

    Science.gov (United States)

    Iaccarino, Luca; Bartoloni, Elena; Gerli, Roberto; Alunno, Alessia; Barsotti, Simone; Cafaro, Giacomo; Gatto, Mariele; Talarico, Rosaria; Tripoli, Alessandra; Zen, Margherita; Neri, Rossella; Doria, Andrea

    2014-12-01

    Idiopathic inflammatory myopathies (IIM) are a rare disease; so far standardized therapy has not been adequately defined by national or international guidelines or recommendations. Corticosteroids are the mainstay of treatment, but these drugs are burdened by several side effects. Thus, additional treatment based on immunosuppressive agents, especially azathioprine, methotrexate, mycophenolate mofetil and cyclosporine, is often needed. This combinate approach both improves the disease response and allows reduction of the dosage of corticosteroids, decreasing the risk of steroid-related long-term complications. Biological agents, particularly B cell depleting agent, are emergent therapeutic tools for refractory cases. Notably, drugs currently used for the therapy of IIM or other rheumatologic and non-rheumatologic conditions can induce myopathy. Drug-induced myopathies represent a considerable part of the complex topic of muscular disorders and should be always considered in the usual diagnostic work-up of a subject with muscle disease. Several mechanisms have been advocated to explain muscular damage induced by a number of drugs and, although a recovery after drug removal is usually observed, severe or persistent myopathy may be observed following the administration of some drugs, particularly in subjects with genetic predisposition. In this review the traditional and novel therapeutic approaches for patients with IIM, particularly biologics, will be discussed and an overview on drug-induced myopathies will also be provided. PMID:26000161

  1. Subcutaneous Histiocytoid Sweet Syndrome Associated with Crohn Disease in an Adolescent

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    Rosa María Fernández-Torres

    2014-01-01

    Full Text Available We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, and upper extremities. Laboratory studies revealed neutrophilia, microcytic anemia, and elevation of both erythrocyte sedimentation rate and C-reactive protein rate. A skin biopsy specimen showed deep dermal and predominantly septal inflammatory infiltrate in the subcutaneous tissue composed of polymorphonuclears, eosinophils, and mononuclear cells of histiocytic appearance. These histiocytoid cells stained positive for myeloperoxidase. Subcutaneous Sweet syndrome is a rare subtype of acute neutrophilic dermatosis, in which the infiltrate is exclusively or predominantly located in the subcutaneous tissue, causing lobular or septal panniculitis. It is often described in patients with an underlying haematological disorder or caused by drugs, but very rare in patients with inflammatory bowel disease, especially in childhood or adolescence. To our knowledge, this is the first case of subcutaneous histiocytoid type in a paediatric patient.

  2. Subcutaneous histiocytoid sweet syndrome associated with crohn disease in an adolescent.

    Science.gov (United States)

    Fernández-Torres, Rosa María; Castro, Susana; Moreno, Ana; Alvarez, Roberto; Fonseca, Eduardo

    2014-01-01

    We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C) from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, and upper extremities. Laboratory studies revealed neutrophilia, microcytic anemia, and elevation of both erythrocyte sedimentation rate and C-reactive protein rate. A skin biopsy specimen showed deep dermal and predominantly septal inflammatory infiltrate in the subcutaneous tissue composed of polymorphonuclears, eosinophils, and mononuclear cells of histiocytic appearance. These histiocytoid cells stained positive for myeloperoxidase. Subcutaneous Sweet syndrome is a rare subtype of acute neutrophilic dermatosis, in which the infiltrate is exclusively or predominantly located in the subcutaneous tissue, causing lobular or septal panniculitis. It is often described in patients with an underlying haematological disorder or caused by drugs, but very rare in patients with inflammatory bowel disease, especially in childhood or adolescence. To our knowledge, this is the first case of subcutaneous histiocytoid type in a paediatric patient. PMID:24839565

  3. Reversion of gingival hyperplasia in a heart transplant patient upon interruption of cyclosporine therapy.

    Science.gov (United States)

    Somacarrera, M L; Lucas, M; Acero, J

    1996-01-01

    A heart transplant patient undergoing a combined cyclosporine and prednisone treatment was monitored during the 18 months following transplantation. A complete oral and dental examination was performed in each of the first six months after transplantation, and then in the 9th, 12th, 15th, and 18th months. The data collected included gingival hyperplasia secondary to cyclosporine use, and clinical and periodontal variables. Histological studies were also conducted on gingival tissue samples in months 1, 3, 9, 15, and 18. Cyclosporine treatment was replaced by azathioprine treatment in month 10 because the patient was experiencing nephrotoxicity. Between months 9 and 18, gingival hyperplasia regressed by 26.5% due to a reduction in the fibrous connective tissue mass, fibroblasts, and inflammatory infiltration. The control group included 13 heart transplant patients subject to equivalent conditions except discontinuance of cyclosporine treatment; seven of the patients had developed hyperplasia by month 9. Average hyperplasia in the control group increased by 2% between months 9 and 18; only one patient showed a 6.2% decrease in hyperplasia. This provides further evidence for the causal relationship between cyclosporine therapy and gingival hyperplasia, and suggests that this side-effect is reversible.

  4. Giant coronary artery aneurysms in juvenile polyarteritis nodosa: a case report

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    Canares Therese L

    2012-01-01

    Full Text Available Abstract Juvenile polyarteritis nodosa (PAN is a rare, necrotizing vasculitis, primarily affecting small to medium-sized muscular arteries. Cardiac involvement amongst patients with PAN is uncommon and reports of coronary artery aneurysms in juvenile PAN are exceedingly rare. We describe a 16 year old girl who presented with fever, arthritis and two giant coronary artery aneurysms, initially diagnosed as atypical Kawasaki disease and treated with IVIG and methylprednisolone. Her persistent fevers, arthritis, myalgias were refractory to treatment, and onset of a vasculitic rash suggested an alternative diagnosis. Based on angiographic abnormalities, polymyalgia, hypertension and skin involvement, this patient met criteria for juvenile PAN. She was treated with six months of intravenous cyclophosphamide and high dose corticosteroids for presumed PAN related coronary vasculitis. Maintenance therapy was continued with azathioprine and the patient currently remains without evidence of active vasculitis. She remains on anticoagulation for persistence of the aneurysms. This case illustrates a rare and unusual presentation of giant coronary artery aneurysms in the setting of juvenile PAN.

  5. The effect of immunosuppressants on experimental infection with Fasciola hepatica.

    Science.gov (United States)

    Corba, J; Spaldonová, R

    1975-01-01

    Results are presented on the effect of immunosuppressive substances such as chlorambucil, cyclophosphamide, azathioprine, amethopterine and a cortizone derivate of betamethasone, on the development of Fasciola hepatica in the rat. The suppression of the immune response of the host to immunosuppressants was reflected in an earlier start of migration of the flukes to the common bile duct, and in an earlier onset of egg production as compared with that in the controls. Of the substances employed, cyclophosphamide and betamethasone were the most effective ones within the period from week 2--6 p.i., which is the time during which the migration of the flukes in the liver parenchyma is highest. Pathological changes in the liver of the animals were less marked than those of the infected controls. Evidence was obtained on an increased pathogenicity of infective larval flukes causing a higher mortality of the hosts in comparison with that of the control animals. On the other hand, the administration of immunosuppressants did neither influence the total number of developed flukes nor the appearance of eosinophilia in the peripheral blood of the treated animals.

  6. Infusion of donor spleen cells and rejection in liver transplant recipients.

    Science.gov (United States)

    Scornik, J C; Lauwers, G Y; Reed, A I; Howard, R J; Dickson, R C; Rosen, C B

    2000-02-01

    Intact or inactivated donor lymphoid cells have been found to downregulate the alloimmune response in a number of experimental models. We conducted a randomized, prospective, double blind, and placebo-controlled trial to determine whether heat-treated donor spleen cells would affect early rejection after liver transplantation. Donor spleen was obtained during organ procurement for 40 patients undergoing liver transplantation. All patients were treated with cyclosporine, azathioprine and steroids. The patients were randomized after surgery to receive either heat-treated (45 degrees C for 1 h) spleen cells or placebo. Patients underwent protocol biopsies at 1 wk, 4 and 12 months, or as needed. Biopsies were reviewed in a blind fashion and scored according to the Banff consensus criteria. Randomization resulted in 19 patients in the spleen cell group and 21 in the placebo group. One-yr graft survival was 94 and 100%, respectively. Early rejection was more frequent in the spleen cell group (61 vs. 35%, p, not significant). The histopathological rejection activity index at 7 d was also higher for the patients in the spleen cell group: 39% of spleen cell treated patients had a score of 4 or higher as opposed to 5% in the placebo group (p spleen cell group versus 1.3 + 1.7 for the placebo group (p = 0.034). It is concluded that heat-treated donor spleen cells given within 24 h after liver transplantation were not clinically beneficial and increased the intensity of rejection in 7-d protocol liver biopsies.

  7. Treatment of eosinophilic cellulitis (Wells syndrome) - a systematic review.

    Science.gov (United States)

    Räßler, F; Lukács, J; Elsner, P

    2016-09-01

    Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well-designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions. PMID:27357601

  8. Treatment for rheumatic polymyalgia

    Directory of Open Access Journals (Sweden)

    Azamat Makhmudovich Satybaldyev

    2013-03-01

    Full Text Available Glucocorticosteroids (GCs that provide a good and rapid clinical effect are the drug of choice to treat rheumatic polymyalgia (RP. A review of English language publications on the treatment of RP is given. Thirty (13 randomized and 17 observational studies of 20 and more patients with RP have been analyzed. Particular emphasis is laid on initial therapy with GCs, evaluation of their different daily doses, schemes for their dosage reduction and treatment termination, and on the frequency of recurrences. Studies dealing with the treatment with prednisone, prednisolone, methylprednisolone, and injectable sustained-release GC formulations are considered. The data of clinical trials of glucocorticoid-sparing agents (methotrexate, azathioprine during early and maintenance therapy are analyzed. The genetically engineered agents (infliximab, etanercept investigated in clinical trials are considered to be as alternatives; a case of using rituximab is described. The role of nonsteroidal anti-inflammatory drugs in the treatment of RP is also evaluated. An algorithm is proposed for the management of a patient with RP.

  9. [The diagnostic value of immunologic findings in the differentiation of chronic liver diseases].

    Science.gov (United States)

    Manns, M; Meyer zum Büschenfelde, K H; Arnold, W

    1988-12-01

    Various types of virus induced and non-virus induced chronic active hepatitis (CAH) as well as chronic non-suppurative destructive cholangitis (PBC) and primary sclerosing cholangitis have to be distinguished. Classical autoimmune type "lupoid" CAH is characterized by antinuclear antibodies (ANA), liver membrane antibodies (LMA) and smooth muscle antibodies (SMA). A second subgroup of autoimmune type CAH is characterized by anti liver kidney-microsomal antibodies (LKM) which are directed against a specific cytochrome p-450 isoenzyme. A third subgroup of autoimmune type CAH is identified by auto-antibodies to a soluble cytoplasmic liver antigen (SLA). Autoimmune type CAH profits from immuno-suppressive therapy, i.e. corticosteroids alone or in combination with azathioprin. Chronic hepatitis B virus infection is nowadays treated with Interferon when HBV-DNA is detectable in serum, duration of liver disease is less than 5 years and superinfection with HDV and HIV can be excluded. PBC is diagnosed through the detection of antimitochondrial antibodies (AMA) and its PBC specific subtypes anti p 62 (M2) and anti p 48. Aetiology and pathogenesis of PBC are still unknown. Liver transplantation is an established therapy for endstage PBC. This is also true for primary sclerosing cholangitis (PSC).

  10. Therapeutic approach to "downhill" esophageal varices bleeding due to superior vena cava syndrome in Behcet's disease: a case report

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    Haghighi Mahshid

    2006-12-01

    Full Text Available Abstract Background One of the rare presentations of superior vena cava syndrome is bleeding of "downhill" esophageal varices (DEV and different approaches have been used to control it. This is a case report whose DEV was eradicated by band ligation for the first time. Case presentation We report a 42-year-old man who is a known case of Behcet's disease. The patient's first presentation was superior vena cava syndrome due to thrombosis followed by bipolar ulcers and arthralgia. He received warfarin, prednisolone and azathioprine. The clinical course of the patient was complicated by one episode of hematemesis without abdominal pain when the patient's PT was in therapeutic range. After resuscitation and correction of PT with fresh frozen plasma transfusion, upper gastrointestinal endoscopy was done. Prominent varices were seen in the upper third of the esophagus, tapering to the middle part without acute bleeding. Stomach and duodenum were normal. Color ultrasonography evaluation of the portal, hepatic and splenic veins was negative for thrombosis. Band ligation was done and the patient's bleeding did not recur. Conclusion Band ligation is a safe and effective method for controlling DEV bleeding in patients with uncorrectable underlying disorders.

  11. Post-transplantation diabetes mellitus

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    N Zbiti

    2012-01-01

    Full Text Available To determine the prevalence of post-kidney transplantation diabetes (PTDM and to assess its risk factors, we retrospectively studied 92 non-diabetic kidney transplant patients. The immunosuppressive drugs used to prevent rejection included prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus and an antimetabolite (azathioprine or mycofenolate mofetil. Diabetes was defined according to the WHO criteria and the American Diabetes Association. The mean age of our patients was 35.8 ± 10.5 years, and there was a clear male predominance (56 men and 36 women. The graft was from living related donor in 71/92 (76% patients. The prevalence of dia-betes in post-kidney transplant was 15.2%. The factors increasing the occurrence of PTDM included advanced age, high doses of steroids and cyclosporine. Management of PTDM included diet modification, oral anti-diabetic and insulin. We conclude that the prevalence of PTDM is significant in our transplant population and risk factors for its development are multiple and require aggressive multifaceted management.

  12. 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

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    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.

  13. New and emerging trends in the treatment of atopic dermatitis

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    Christina M Gelbard

    2009-01-01

    Full Text Available Christina M Gelbard1, Adelaide A Hebert1,21Departments of Dermatology; 2Pediatrics, University of Texas-Houston, Houston, TX, USAAbstract: Atopic dermatitis is a chronic, inflammatory skin condition that affects 10% to 20% of children and 1% to 3% of adults in the US. Symptoms often result in sleeplessness, psychological stress, poor self-esteem, anxiety, and poor school or work performance. The cost of atopic dermatitis is estimated to be US$0.9 to 3.8 billion every year. Topical steroids are first-line treatment for atopic dermatitis, and recent advances in vehicle technologies have resulted in improved patient tolerability and compliance. Topical calcineurin inhibitors are also safe and effective topical treatments for atopic dermatitis, and provide an additional therapeutic option for patients with this disease. Systemic immunomodulators are used in the treatment of severe refractory disease. Cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and interferon gamma have been used in the management of severe atopic dermatitis. This review highlights the current and emerging trends in the treatment of atopic dermatitis.Keywords: atopic dermatitis, topical corticosteroids, calcineurin inhibitors, methotrexate, cyclosporine, mycophenolate mofetil, IFN-γ

  14. Identification of a major Leu 7/OKT 8 positive T-lymphocyte subpopulation in renal transplant patients pre-treated with total lymphoid irradiation

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    Waer, M.; Ceuppens, J.L.; Vanrenterghem, Y.; Schueren, E. van der; Michielsen, P.; Vandeputte, M.

    1986-01-01

    When pretreated with total lymphoid irradiation, renal allograft recipients have an increased percentage of OKT 8 positive (cytotoxic/suppressor) T cells among their peripheral blood T lymphocytes (PBL) (56 +- 21%) and also of Leu 7 PBL (47 +- 18%). In contrast, transplant patients treated with azathioprine or cyclosporine A have percentages of OKT 8 and Leu 7 positive PBL, similar to control persons (respectively 29 +- 13, 33 +- 10, 30 +- 10 for the OKT 8+ cells and 8 +- 7, 11 +- 6 and 15 +- 9 for the Leu 7+ cells). After purification, about two thirds (70%) of the OKT 8 positive, OKT 3 positive, T lymphocytes of TLI patients were shown to co-express the Leu 7 antigen. It is concluded that after TLI, an increase of OKT 3+, OKT 8+ and Leu 7 + lymphocytes takes place, a subset previously described to be present in low numbers in control persons and whose function is still unclear. This expansion after TLI should allow functional identification of this subset and might contribute to the understanding of the immunosuppressive effects of TLI.

  15. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-04-01

    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.

  16. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-04-01

    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.

  17. A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function.

    Science.gov (United States)

    Wilkie, M E; Beer, J C; Evans, S J; Raftery, M J; Lord, R H; Moore, R; Marsh, F P

    1994-01-01

    A double-blind, randomized, placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin (CsA), prednisolone and azathioprine. Fifty adult cadaveric renal allograft recipients were randomized to placebo (group P n = 17), nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 48 h, followed by matching placebo for 3 months (group NS n = 16) or nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 3 months (group NL n = 17). Donor and recipient exclusion criteria included recent calcium antagonist treatment. At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS (mean +/- SD 61 +/- 28 versus 34 +/- 25 ml/min/1.73 m2; P nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin.

  18. Cyclosporine-pancuronium interaction in a patient with a renal allograft.

    Science.gov (United States)

    Crosby, E; Robblee, J A

    1988-05-01

    A case is described of a 54-year-old 55 kg patient who presented for clipping of a middle cerebral aneurysm two years after a successful renal allograft. Immunosuppression was maintained with azathioprine 100 mg daily, cyclosporine 300 mg daily and prednisone 10 mg daily. The patient had chronic hypertension controlled with nifedipine 40 mg daily and furosemide 20 mg daily. The cyclosporine level taken on the morning of surgery was 166 micrograms.L-1. Induction of anaesthesia consisted of fentanyl 350 micrograms, thiopentone 125 mg and pancuronium 5.5 mg. Anaesthesia was maintained with nitrous oxide 70 per cent in oxygen and isoflurane 0.5-1.5 per cent. No additional doses of pancuronium were given during the four hour surgical procedure. At the end of surgery, four twitches were present with train-of-four stimulation, but evidence of residual muscle paralysis was present. Residual neuromuscular blockade was reversed with atropine 1.2 mg and neostigmine 2.5 mg. Residual paralysis was present in the Recovery Room and edrophonium 10 mg was given prior to extubation. Clinical testing demonstrated adequate reversal of neuromuscular blockade. Twenty minutes following extubation, increasing respiratory distress was noted. There was clinical evidence of muscle paralysis. The patient was re-intubated. It is proposed that cyclosporine potentiated the pancuronium blockade producing prolonged neuromuscular relaxation resulting in residual paralysis following surgery. The potential interactions of cyclosporine and muscle relaxants deserve further study.

  19. Comparative effects of enalapril and nifedipine on renal hemodynamics in hypertensive renal allograft recipients.

    Science.gov (United States)

    Abu-Romeh, S H; el-Khatib, D; Rashid, A; Patel, M; Osman, N; Fayyad, M; Scheikhoni, A; Higazi, A S

    1992-04-01

    The comparative effects of enalapril (E) and nifedipine (N) on renal hemodynamics were assessed in twenty-two moderately hypertensive, cadaveric renal transplant patients who were maintaining stable renal function. Fourteen patients were on cyclosporin (CSA) and eight were receiving azathioprine with prednisolone (AZA). In each patient effective renal plasma flow (ERPF) was determined four times, first baseline, second with E, third as another baseline after a washout period, and fourth with N; and renal vascular resistance (RVR) was derived in each. ERPF and RVR were significantly compromised in the CSA group (202 +/- 55 ml/min and 65 +/- 18 mmHg/ml/min) compared to the AZA group (302 +/- 99 and 43 +/- 15 respectively). During E therapy, RVR further increased in the CSA group to 82 +/- 37 while it decreased in the AZA group to 31 +/- 7 (both changes were significant when compared to their respective baseline values). N, on the other hand, only significantly lowered RVR in the AZA group. Furthermore, two patients, one from each group, developed acute reversible renal failure shortly after E therapy. However, both agents were effective in lowering blood pressure to a comparable degree in both groups. In conclusion, our data showed a somewhat less favourable renal hemodynamic response to short-term enalapril therapy in hypertensive renal transplant patients maintained on CSA. However, the significance of such hemodynamic changes for long-term renal function remains uncertain.

  20. Renal hemodynamics in hypertensive renal allograft recipients: effects of calcium antagonists and ACE inhibitors.

    Science.gov (United States)

    Grekas, D; Dioudis, C; Kalevrosoglou, I; Alivanis, P; Derveniotis, V; Tourkantonis, A

    1996-06-01

    Hypertension present in more than 50% of successfully renal transplanted patients and its prevalence has slightly increased since the introduction of cyclosporine A. Twenty patients, 9 women and 11 men aged from 30 to 58 years, with stable cadaveric renal allograft function and moderate to severe hypertension, were included in the study. Renal artery graft stenosis causing hypertension were excluded. All patients were given triple drug immunosuppressive treatment with methylprednisolone, azathioprine and cyclosporine A (CsA) and their hypertension was treated with a nifedipine dose of 20 mg twice daily. To evaluate the effect of ACE inhibitors on renal hemodynamics and hypertension, a 4 mg/daily dose of perindopril was added to the above regimen for two months. Effective renal plasma flow (ERPF) decreased from 208 +/- 54 to 168 +/- 61 ml/min and renal vascular resistance (RVR) increased from 75 +/- 12 to 88 +/- 17 mm Hg/ml/min (P nifedipine. It is suggested that the combination of both antihypertensive agents was more effective than monotherapy with nifedipine in controlling blood pressure, but less favorable on the renal hemodynamic response in hypertensive renal transplant patients who were maintained on CsA.

  1. Cyclosporine A enhances platelet aggregation.

    Science.gov (United States)

    Grace, A A; Barradas, M A; Mikhailidis, D P; Jeremy, J Y; Moorhead, J F; Sweny, P; Dandona, P

    1987-12-01

    In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

  2. Pulse cyclophosphamide therapy for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Zsolt Barta; László Tóth; Margit Zeher

    2006-01-01

    AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD).METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800mg) per month.RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d).CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.

  3. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    JohannesMeier; AndreasSturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring re- current inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complica- tions of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  4. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Meier; Andreas Sturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice- orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  5. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    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

  6. Behçet′s uveitis

    Directory of Open Access Journals (Sweden)

    Tugal-Tutkun Ilknur

    2009-01-01

    Full Text Available Behcet′s disease is a multisystem inflammatory disorder that is most common in countries along the ancient "Silk Road". The eye is the most commonly involved vital organ in Behηet′s patients and the typical form of involvement is a relapsing remitting panuveitis and retinal vasculitis. Uveitis is the initial manifestation of the disease in 10-15% of the patients. Anterior uveitis is always nongranulomatous. Diffuse vitritis, retinal infiltrates, sheathing of predominantly retinal veins, and occlusive vasculitis are the typical signs of posterior segment inflammation. Spontaneous resolution of acute inflammatory signs is a diagnostic feature. Fundus fluorescein angiography is the gold standard in monitoring inflammatory activity. Laser flare photometry is a useful noninvasive tool since flare readings correlate with fluorescein angiographic leakage. The most common complications are cataract, maculopathy, and optic atrophy. Male patients have a more severe disease course and worse visual prognosis. Immunomodulatory therapy is indicated in all patients with posterior segment involvement. Corticosteroids combined with azathioprine and/or cyclosporine is used initially. Biologic agents, including interferon alfa and infliximab, are used in resistant cases. Visual prognosis has improved in recent years with an earlier and more aggressive use of immunomodulatory therapy and the use of biologic agents in resistant cases.

  7. Noncirrhotic Portal Hypertension due to Nodular Regenerative Hyperplasia Treated with Surgical Portacaval Shunt

    Directory of Open Access Journals (Sweden)

    Lisa M. Louwers

    2012-01-01

    Full Text Available Nodular regenerative hyperplasia (NRH is an uncommon condition, but an important cause of noncirrhotic intrahepatic portal hypertension (NCIPH, characterized by micronodules of regenerative hepatocytes throughout the liver without intervening fibrous septae. Herein, we present a case of a thirty-seven-year-old female with systemic lupus erythematosus (SLE who was discovered to have significant esophageal varices on endoscopy for dyspepsia. Her labs revealed a slight elevation in the alkaline phosphatase and mild thrombocytopenia. Abdominal MRI revealed seven focal hepatic masses, splenomegaly, no ascites, and a patent portal vein. Ultrasound-guided core biopsy was reported as focal nodular hyperplasia. However, her varices persisted despite treatment with beta-blockers and four additional upper endoscopies with banding. She was subsequently referred for a surgical opinion. At that time, given her history of SLE, azathioprine use, and portal hypertension, suspicion for NRH was raised. Given her normal synthetic function and lack of parenchymal liver disease, the patient was offered surgical shunting. During shunt surgery, a liver wedge biopsy was also performed and this confirmed NRH. An upper endoscopy six weeks after shunting verified complete resolution of varices. Currently, fifteen months after surgery duplex ultrasonography demonstrates shunt patency and the patient is without recurrence of her portal hypertension.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

  10. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    Science.gov (United States)

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse. PMID:26804376

  11. 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.

  12. Treatment of intractable lupus nephritis with total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. 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.

  14. A subset of ulcerative colitis with positive proteinase-3antineutrophil cytoplasmic antibody

    Institute of Scientific and Technical Information of China (English)

    Jin Xu; Chuan-Hua Yang; Xiao-Yu Chen; Xu-Hang Li; Min Dai; Shu-Dong Xiao

    2008-01-01

    A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies.We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission.Four of these 5 patients were steroid-dependence,and immunosuppressants, such as azathioprine and cyclophosphamide, were ineffective. In 3 patients,only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates that ulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients,with additional advantages of having no noticeable sideeffects and less financial burden.

  15. Pediatric live-donor kidney transplantation in Mansoura Urology & Nephrology Center: a 28-year perspective.

    Science.gov (United States)

    El-Husseini, Amr A; Foda, Mohamed A; Bakr, Mohamed A; Shokeir, Ahmed A; Sobh, Mohamed A; Ghoneim, Mohamed A

    2006-10-01

    Our objective was to evaluate our overall experience in pediatric renal transplantation. Between March 1976 and March 2004, 1,600 live-donor kidney transplantations were carried out in our center; 216 of the patients were 18 years old or younger (mean age 12.9 years). There were 136 male patients and 80 female patients. The commonest causes of end-stage renal disease (ESRD) were renal dysplasia (22%), nephrotic syndrome (20%), hereditary nephritis (16%), and obstructive uropathy (16%). Of the donors, 94% were one-haplotype matched and the rest were identical. Pre-emptive transplantation was performed in 51 (23%) patients. Triple-therapy immunosuppression (prednisone + cyclosporine + azathioprine) was used in 78.2% of transplants. Rejection-free recipients constituted 47.7%. Hypertension (62%) was the commonest complication. A substantial proportion of patients (48%) were short, with height standard deviation score (SDS) less than -1.88. The overall infection rate was high, and the majority (53%) of infections were bacterial. The graft survival at 1 year, 5 years and 10 years were 93.4%, 73.3% and 48.2%, respectively, while the patients' survival at 1, 5 and 10 years were 97.6%, 87.8% and 75.3%, respectively. Despite long-term success results of pediatric renal transplantation in a developing country, there is a risk of significant morbidity. PMID:16791608

  16. Refractory Celiac Disease

    Directory of Open Access Journals (Sweden)

    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. Gastrointestinal surgical emergencies following kidney transplantation.

    Science.gov (United States)

    Bardaxoglou, E; Maddern, G; Ruso, L; Siriser, F; Campion, J P; Le Pogamp, P; Catheline, J M; Launois, B

    1993-05-01

    This study reports major gastrointestinal complications in a group of 416 patients following kidney transplantation. Three hundred and ninety-nine patients received a cadaveric kidney while the other 17 received a living related organ. The immunosuppressive regimen changed somewhat during the course of the study but included azathioprine, prednisolone, antilymphocyte globulin, and cyclosporin. Perforations occurred in the colon (n = 6), small bowel (n = 4), duodenum (n = 2), stomach (n = 1), and esophagus (n = 1). There were five cases of acute pancreatitis, four of upper gastrointestinal and two of lower intestinal hemorrhage, two of acute appendicitis, one of acute cholecystitis, one postoperative mesenteric infarction, and two small bowel obstructions. Fifty percent of the complications occurred while patients were being given high-dose immunosuppression to manage either the early postoperative period or episodes of acute rejection. Ten percent of the complications had an iatrogenic cause. Of the 31 patients affected, 10 (30%) died as a direct result of their gastrointestinal complication. This high mortality appears to be related to the effects of the immunosuppression and the associated response to sepsis. Reduction of these complications can be achieved by improved surgical management, preventive measures, prompt diagnosis, and a reduced immunosuppressive protocol.

  18. Intestinal pseudo-obstruction in inactive systemic lupus erythematosus: An unusual finding

    Institute of Scientific and Technical Information of China (English)

    Giulia; Leonardi; Nicola; de; Bortoli; Massimo; Bellini; Maria; Gloria; Mumolo; Francesco; Costa; Angelo; Ricchiuti; Stefano; Bombardieri; Santino; Marchi

    2010-01-01

    Chronic intestinal pseudo-obstruction (CIP) is an infre-quent complication of an active systemic lupus erythema-tosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (ECLAM score 2) was hospitalized with postprandial fullness, vomiting, abdominal bloating and abdominal pain. She had had no bowel movements for five days. Plain abdominal X-ray revealed multiple fluid levels and dilated small and large bowel loops with air-fluid levels. Intestinal contrast radiology detected dilated loops. CIP was diagnosed. The patient was treated with prokinetics, octreotide, claritromycin, rifaximin, azathioprine and tegaserod without any clinical improvement. Then methylprednisolone (500 mg iv daily) was started. After the first administration, the patient showed peristaltic movements. A bowel movement was reported after the second administration. A plain abdominal X-ray revealed no air-fluid levels. Steroid therapy was slowly reduced with complete resolution of the symptoms. The patient is still in a good clinical condition. SLE-related CIP is generally reported as a complication of an active disease. In our case, CIP was the only clinical demonstration of the SLE.

  19. Therapeutic relevance of HRCT findings from a pneumological viewpoint; Therapeutische Relevanz des HRCT-Befundes aus pneumologischer Sicht

    Energy Technology Data Exchange (ETDEWEB)

    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

  20. Analysis of malignancies in patients after heart transplantation with subsequent immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2014-12-01

    Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Berthold Klein,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch11Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyObjective: The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR containing immunosuppressive regimen.Methods: A total of 381 patients (age ≥18 years receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA and azathioprine (AZA was replaced by CsA and mycophenolate mofetil (MMF in 2001 and by tacrolimus (TAC and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus were applied since 2003.Results: Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total. Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%, 56 patients with noncutaneous malignancy only (14.7%, and 16 patients with both cutaneous and noncutaneous malignancy (4.2%. Statistically significant

  1. Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study Cloroquina para manutenção da remissão da hepatite auto-imune: resultado de estudo piloto

    Directory of Open Access Journals (Sweden)

    Marcos Mucenic

    2005-12-01

    Full Text Available BACKGROUND: Due to the risks related to long-term treatment with prednisone and azathioprine, most clinicians try to withdraw these drugs when patients with autoimmune hepatitis are in remission. However, there is a high probability of relapse, and most patients end up receiving maintenance treatment. AIM: To evaluate the safety and efficacy of maintenance treatment with chloroquine in the prevention of autoimmune hepatitis relapses. METHODS: Classical treatment was stopped after achievement of biochemical and histological remission of autoimmune hepatitis. Chloroquine diphosphate, 250 mg daily, was given for at least 12 months or until the occurrence of relapses defined by levels of aminotransferases at least twice the upper normal values. RESULTS: Fourteen patients were consecutively treated and compared with 18 historical controls. There was a 6.49 (1.38-30.30 greater chance of relapse in the historical controls when compared with patients treated with chloroquine (72.2% x 23.5%; 0.031. CONCLUSIONS: The group treated with chloroquine had a lower frequency of relapses. Chloroquine was safe in patients with autoimmune hepatitis and hepatic cirrhosis without decompensation, on 250 mg daily up to 2 years. These preliminary results provide a basis for upcoming controlled studies comparing chloroquine with placebo or for maintenance treatment with prednisone and/or azathioprine for the prevention of autoimmune hepatitis relapses.RACIONAL: Em razão dos riscos relacionados ao tratamento prolongado com prednisona e azatioprina, tenta-se a retirada dessas drogas em pacientes com hepatite auto-imune em remissão. Como há alta taxa de recidiva, a maioria dos pacientes recebe tratamento por tempo indefinido. OBJETIVO: Avaliar a segurança e a eficácia do tratamento de manutenção com cloroquina na prevenção de recidiva da hepatite auto-imune. MÉTODOS: O tratamento convencional foi suspenso após obtenção de remissão bioquímica e histol

  2. 原位肝移植治疗肝门部胆管癌二例报告%Orthotopic liver transplantation for the treatment of klatskin tumor

    Institute of Scientific and Technical Information of China (English)

    刘永锋; 何三光; 刘浩; 张佳林; 刘树荣; 宋少伟; 梁健; 王凤山; 崔宏; 沈魁

    1999-01-01

    Objective To investigate whether or not that klatskin tumor is adapt to liver transplantation.Methods In April 1995 and Nov.1997,orthotopic liver transplantation was successfully performed on 2 cases of ldatskin tumor.The liver graft was harvested bv combined rapid multiple organ harvesting technique,flushed and preserved with UW solution.Veno-venous bypass was processed with BioMedicus pump in anhepatic phase.Immunosuppressive protocol WaS cyclosporin A,prednisone and azathioprine,while azathioprine wan replaced by cellcept in case 2.Results Liver function recovered rapidly with an obvious regression of jaundice.Hemoconcentration occurred in case one on the 4 th postoperative day,followed by cerebral thrombosis and lung infection,and died of multiple system organ failure on the 12 th postoperative day.Another one was discharged 4 weeks postoperation,but died of tumor recurrence after 5 months.Conclusion The Bismuth IV hilar bile duct cancer is adapt to liver transplantation.But how to assess whether or not there are micro-metastases before operation and effectively control tumor recurrence postoperation are important projections needed to resolve.%目的 探讨肝门部胆管癌是否为肝移植的适应证.方法 为2例肝门部胆管癌的患者施行了同种原位肝移植术.供肝切取采用腹腔器官联合快速切取法,灌洗液及保存液为UW液.无肝期采用Bio-Medicus转流泵行体外静脉转流.术后免疫抑制治疗,例1采用环孢素A、泼尼松和硫唑嘌呤三联用药,例2采用霉酚酸酯代替硫唑嘌呤.结果 移植后肝功能恢复正常,黄疸减退,但例1术后4天因血液浓缩而出现脑栓塞,肺内感染,术后12天死于多器官功能衰竭;例2移植后4周顺利出院,但5个月后死于肿瘤复发.结论 肝门部胆管癌BismuthⅣ型仍不失为肝移植的适应证,但术前判定是否有微转移灶及术前、术中与术后有效的辅助治疗、防止肿瘤复发等是需要解决的重要课题.

  3. 老年特发性血小板减少性紫癜患者的临床观察%Clinical study on the elderly patients with idiopathic/immune thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    范芸; 常乃柏; 邢宝利; 裴蕾; 李元明; 顾惜春; 许晓东

    2008-01-01

    目的 总结老年特发性血小板减少性紫癜(ITP)患者的发病特点、治疗及临床转归.方法 回顾分析1992-2007年我院住院治疗的老年ITP患者的临床资料,并与同期住院的非老年患者的临床资料进行对照.结果 老年患者(老年组)43例,男性16例,女性27例;随访时间1个月~15年,存活35例.43例患者中,7例血小板持续(30~50)×109/L,出血不显著,未予以治疗;36例首选泼尼松治疗,敏感型25例(69.4%),以完全反应或部分反应健康存活;脾切除或栓塞4例,3例血小板恢复正常;对于泼尼松治疗不敏感者分别使用免疫抑制剂,其中硫唑嘌呤21例,环孢A23例,长春新碱3例及环磷酰胺9例,硫唑嘌呤、环孢A疗效优于长春新碱及环磷酰胺.进展为难治性ITP5例,难治率为13.9%;进展为未定性单克隆免疫球蛋白增多症(MGUS)和淋巴瘤各1例.死亡8例,死于外伤感染引发的心肺功能衰竭4例,肿瘤3例,脑出血1例.结论 老年ITP患者临床表现不典型,致命性出血的风险低,对免疫抑制剂的反应与非老年组近似,治疗宜个体化.%Objective To explore the clinical characteristics,therapy reactions and prognosis of the elderly patients with idiopathic thrombocytopenic purpura(ITP). Methods A total of 43elderly ITP patients(age≥60 years old)including 16 men and 27 women were reviewed and further followed up for 1 month to 15 years. Results Until June 2007,35 elderly ITP patients survived,platelet counts were sustained(30-50)×109/L in 7 cases,but no significant bleeding was found.Thirty-six patients had adrenocorticosteroid therapy first, 25 patients were sensitive to adrenocorticosteroid therapy,4 patients underwent splenectomy,and 3 patients achieved a normal platelet count. Immunosuppressive agents(vinscristine,cyclophosphamide, azathioprine and Cyclosporin A)treatments were held in 5 6 case-times,Cyclosporin A and azathioprine were more effective than vinscristine and cyclophosphamide

  4. Doença de Neuro-Behçet de início na infância Neuro-Behçet's Disease in childhood-onset

    Directory of Open Access Journals (Sweden)

    Teresa Cristina Martins Vicente Robazzi

    2005-08-01

    Full Text Available Os autores descrevem o caso de um adolescente, que iniciou com quadro clínico de uveíte bilateral e aftas na mucosa oral aos 13 anos de idade. Nesse momento foi estabelecido o diagnóstico de doença de Behçet, evoluindo dois anos após com hemiparesia aguda e deficit motor à direita. A ressonância magnética do crânio evidenciou sinais de vasculite em atividade. O tratamento inicial com ciclofosfamida não se mostrou eficaz, requerendo o uso de clorambucil e posteriormente da azatioprina oral. A doença de Behçet apresenta envolvimento multissistêmico com manifestações oculares, cutânea, ocular, intestinal, articular, vascular, urogenital e neurológica. As manifestações neurológicas têm início mais freqüentemente na população adulta e excepcionalmente na infância e adolescência, representando uma importante causa de invalidez e morte.The authors describe a thirteen years old teenager who had bilateral uveitis and recurrent oral aphthous ulcers. At that moment, Behçet's disease was diagnosed, and after a two-year follow-up, acute right hemiparalysis and motor deficit occured. Magnetic Resonance Imaging of the skull showed signs of active vasculitis. Initial treatment with cyclophosfamide wasn't efficient, requiring the use of clorambucil and, posteriorly, oral azathioprine. Behçet's disease presents with multisystemic manifestations such as ocular, cutaneous, oral, intestinal, articular, vascular, urogenital and neurologic disorders. Neurological manifestations usually begin in adult life and, exceptionally, in childhood and adolescence, representing an important cause of disability and mortality.

  5. Use of the tumor necrosis factor-blockers for Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Alan BR Thomson; Milli Gupta; Hugh J Freeman

    2012-01-01

    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.

  6. Long-term outcome of everolimus treatment in transplant patients

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    Salvadori M

    2011-05-01

    Full Text Available Maurizio Salvadori, Elisabetta BertoniRenal Unit, Careggi University Hospital, Florence, ItalyAbstract: The authors review the use of everolimus in long-term studies both in renal and heart transplantation. The pharmacokinetic and pharmacodynamic differences between everolimus and its parent drug, sirolimus are discussed. The improved pharmacokinetic, in particular the improved bioavailability, the reduced half-time and the reduced binding to plasma protein makes everolimus the first choice among the proliferation signal inhibitors. Everolimus is given in almost all studies in association with cyclosporine, but fixed doses of this drug can cause nephrotoxicity. The first studies used everolimus and CsA in fixed doses, but later studies with reduced CsA doses revealed which revealed improved outcomes. Finally, therapeutic drug monitoring became the better choice for both drugs. Recently very high everolimus exposure allowed the use of very low CsA exposure with improvement of the worse side effects linked to the CsA standard dose. The Zeus study revealed a complete and safe CsA withdrawal, thanks to everolimus and mycophenolic acid. In heart transplantation, everolimus resulted in improved outcomes with respect to antiproliferative drugs such as mycophenolic acid and azathioprine. Along with antirejection properties, everolimus provided evidence for antiproliferative effects on several cells. This resulted in fewer viral infections (mainly CMV, anti-atherosclerotic properties (mainly important in heart transplantation, and antineoplastic effect. The latter activity resulted in lower cancer incidence in transplant patients treated by everolimus. An important piece of evidence for this activity is documented by the use of everolimus in the treatment of some cancers, including renal cancer, neuroendocrine cancers and hepatocellular cancers, also outside the field of transplantation.Keywords: everolimus, renal transplantation, heart transplantation

  7. Diagnostic Dilemma in a Patient with Jaundice: How to Differentiate between Autoimmune Pancreatitis, Primary Sclerosing Cholangitis and Pancreas Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  8. Crohn's Disease and Acute Pancreatitis: A Review of Literature

    Directory of Open Access Journals (Sweden)

    Sarfaraz Jasdanwala

    2015-03-01

    Full Text Available Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40- 50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.

  9. Management of Inflammatory Bowel Disease during Pregnancy and Breastfeeding Varies Widely: A Need for Further Education

    Science.gov (United States)

    Goodman, Karen Jean; Hegadoren, Kathleen M.; Dieleman, Levinus Albert; Fedorak, Richard Neil

    2016-01-01

    Background. Inflammatory bowel disease (IBD) affects patients in their young reproductive years. Women with IBD require maintenance therapies during pregnancy and breastfeeding. However, physician management of IBD during pregnancy and breastfeeding has not been well characterized. Objective. To characterize physician perceptions and management of IBD during pregnancy and breastfeeding. Methods. A cross-sectional survey of Canadian physicians who are involved in the care of women with IBD was conducted. The survey included multiple-choice and Likert scale questions about perceptions and practice patterns regarding the management of IBD during pregnancy and breastfeeding. Results. 183 practicing physicians completed the questionnaire: 97/183 (53.0%) gastroenterologists; 75/183 (41.0%) general practitioners; and 11/183 (6.0%) other physicians. Almost half (87/183, 47.5%) of the physicians felt comfortable managing pregnant IBD patients. For specified IBD medications, proportions of physicians who indicated they would continue them during pregnancy were as follows: sulfasalazine, 47.4%; oral mesalamine, 67.0%; topical mesalamine, 70.3%; oral prednisone, 68.0%; topical prednisone, 78.0%; oral budesonide, 61.6%; topical budesonide, 75.0%; ciprofloxacin, 15.3%; metronidazole, 31.4%; azathioprine, 57.1%; methotrexate, 2.8%; infliximab, 55.6%; adalimumab, 78.1%. Similar proportions of physicians would continue these medications during breastfeeding. A higher proportion of gastroenterologists than nongastroenterologists indicated appropriate use of these IBD medications during pregnancy and breastfeeding. Conclusions. Physician management of IBD during pregnancy and breastfeeding varies widely. Relative to other physicians, responses of gastroenterologists more frequently reflected best practices pertaining to medications for control of IBD during pregnancy and breastfeeding. There is a need for further education regarding the management of IBD during pregnancy and

  10. Oral available agents in the treatment of RRMS

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    Aupérin T

    2013-10-01

    Full Text Available Thierry Aupérin Medical Communications, Global MS Medical Affairs, Genzyme Corporation, Cambridge, MA, USAWe read with interest the article by Drs Thöne and Ellrichmann entitled "Oral available agents in the treatment of relapsing remitting multiple sclerosis: an overview of merits and culprits" recently published in Drug, Healthcare and Patient Safety.1 The review provides a valuable overview of a number of new therapeutic options for multiple sclerosis (MS, with a focus on proposed mechanisms of action and efficacy and safety profiles of the respective agents.In reading the article, however, we did note a number of errors pertaining to teriflunomide, a once-daily oral immunomodulator approved in several countries for the treatment of relapsing forms of MS (RMS and relapsing-remitting MS (RRMS. The most significant error pertains to a statement made within the safety section, which states: "Serious adverse effects (AEs included pathological liver function, neutropenia, and trigeminal neuralgia as well as one case of progressive multifocal leukoencephalopathy (PML in a patient with systemic lupus erythematosus." We would like to draw the authors’ attention to the fact that this case of PML pertains to the use of the related drug, leflunomide, and not teriflunomide as suggested. It is important to note that leflunomide is licensed to treat active rheumatoid arthritis in adults, and has not been evaluated or approved for the treatment of MS; as such it is inappropriate to extrapolate this observation to the use of teriflunomide. Furthermore, the case of PML cited in the article is complicated by the fact that the patient received prior multiple immunosuppressant therapies before leflunomide (ie, prednisone, azathioprine, chloroquine, danazol, cyclosporin A and methotrexate, which may have contributed to the development of PML.View original paper by Thöne and Ellrichmann.

  11. 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

  12. Tratamento da arterite de Takayasu Takayasu’s arteritis treatment

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    Alexandre Wagner Silva de Souza

    2006-06-01

    Full Text Available A arterite de Takayasu (AT é uma vasculite granulomatosa crônica que envolve a aorta e seus principais ramos. A monitoração da atividade da doença e o melhor esquema terapêutico ainda têm sido um desafio para todos os que tratam estes pacientes. Corticosteróides e imunossupressores vêm sendo utilizados na prática clínica diária com resultados nem sempre animadores. Apesar de não haver estudos controlados que abordem o tratamento da AT, diferentes estudos observacionais descrevem a resposta de pacientes com AT ao uso de corticosteróides, metotrexato (MTX, azatio-prina e ciclofosfamida. Após a introdução da terapia biológica, novas perspectivas têm surgido para os pacientes com AT refratários aos esquemas terapêuticos tradicionais.Takayasus’s arteritis is a chronic granulomatous vasculitis involving the aorta and its main branches. Monitoring disease activity and the choice for the best therapy has been major challenger faced by all physicians who treat these patients. Corticosteroids and immunosuppressive therapy have been used in daily medical practice, but results have not always been encouraging. Although there are no controlled studies evaluating the treatment of Takayasu’s arteritis, observational studies have described the response to the use of corticosteroids, methotrexate, azathioprine and cyclophosphamide. The emerging of biological therapy has brought new perspective for Takayasu’s patients who are refractory to conventional therapy.

  13. Theileriosis in six dogs in South Africa and its potential clinical significance

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    Chantal T. Rosa

    2014-02-01

    Full Text Available Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4and Theileria equi (n = 2 were detected by a polymerase chain reaction (PCR-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs, bleeding tendencies (five out of six dogs and lethargy (three out of six dogs. All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.

  14. Historical reflections on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Ian R Mackay

    2008-01-01

    Autoimmune hepatitis (AIH),initially known as chronic active or active chronic hepatitis (and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody (ANA),smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being (relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

  15. 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.

  16. Bullous Pemphigoid With a Dual Pattern of Glomerular Immune Complex Disease.

    Science.gov (United States)

    Hoorn, Ewout J; Taams, Noor E; Hurskainen, Tiina; Salih, Mahdi; Weening, Jan J; Jonkman, Marcel F; Pas, Hendri H; Schreurs, Marco W J

    2016-02-01

    A 75-year-old man presented with a blistering skin disease and nephrotic syndrome. Bullous pemphigoid was diagnosed by linear immunoglobulin G (IgG) and C3 staining along the basement membrane zone of a skin biopsy specimen and by the presence of circulating IgG recognizing the 180-kDa bullous pemphigoid antigen (BP180; type XVII collagen). A kidney biopsy specimen showed endocapillary inflammation without crescents. Direct immunofluorescence showed strong IgG and C3 staining in a combined granular and linear pattern along the glomerular basement membrane. Electron microscopy showed subepithelial deposits. In serum, no antibodies against the Goodpasture antigen (type IV collagen) or phospholipase A2 receptor were detected. Indirect immunofluorescence studies using the patient's serum showed a strikingly linear but not granular IgG pattern along the epithelial basement membranes of monkey esophagus and kidney. Although type XVII collagen was recently identified in the glomerulus, the patient's serum did not produce a 180-kDa band on immunoblot of kidney tissue and still stained glomeruli of BP180 knockout mice by indirect immunofluorescence. The patient was treated with prednisone and azathioprine, which resulted in complete remission of skin and kidney manifestations. Although bullous pemphigoid has been reported previously in association with anti-glomerular basement membrane disease or membranous nephropathy, this case demonstrates both elements in 1 patient. This concurrence and the linear pattern on indirect immunofluorescence support the possibility of cross-reactive or parallel autoantibodies to basement membranes with a secondary membranous component. PMID:26616334

  17. Research Progress of Biological Agents in the Treatment of Systemic Lupus Erythematosus%生物技术药物治疗系统性红斑狼疮的研究进展

    Institute of Scientific and Technical Information of China (English)

    周立偲; 田浤; 高向东; 何书英

    2014-01-01

    系统性红斑狼疮是一种侵犯身体多脏器的典型的自体免疫疾病,对人体危害极大。严重肾脏受累的系统性红斑狼疮患者如果不给予适当治疗会进展到末期肾病,甚至死亡。系统性红斑狼疮的治疗是现今研究关注的热点。现有的激素治疗由于副作用以及对病程恶化无显著改善而限制了其临床应用。生物技术药物因其良好的靶向性为治疗系统性红斑狼疮提供了新的思路,其安全性和有效性已在临床试验中证明。本文对生物技术药物用于治疗系统性红斑狼疮的研究作一综述。%This paper aims to review the current development of therapies of systemic lupus erythe-matosus (SLE) based on biological agents. The conventional immunosuppressive therapies such as azathio-prine, cyclophosphamide and ormethotrexate reduce disease activity and improves the patients' general health conditions. However, these treatments have possible side effects. According to domestic and foreign literatures, new developed biological agents against SLE are summarized as follows: biologic agents that block B-cell activation; biologic agents that induce tolerance; biologic agents that induce antibody targeting IFN; biologic agents that target anti-dsDNA, Antigen-Based Heteropolymer. From these results it could be concluded that biological agents open a new path for the treatment of SLE.

  18. 葡萄膜炎的临床治疗研究进展%Recent advances in studies of clinical treatment of uveitis

    Institute of Scientific and Technical Information of China (English)

    郑曰忠

    2008-01-01

    葡萄膜炎是临床上常见的一类免疫相关性炎性疾病.糖皮质激素是葡萄膜炎的首选治疗药物;而对于一些顽固性或难治性葡萄膜炎患者可联合环孢素、麦考酚酸酯、硫唑嘌呤或环磷酰胺等免疫调节剂治疗;抗肿瘤坏死因子制剂、干扰素α及白细胞介素2受体拮抗剂等生物制剂也显示有独特疗效;玻璃体内注射糖皮质激素缓释剂或玻璃体切除手术对某些特殊类型的葡萄膜炎及其并发症有一定疗效.近年来,眼科学者们开展了一些新的免疫调节或者手术方法用以治疗葡萄膜炎眼病.%Uveitis is a common immune-related intraocular inflammation,the topical or systemic corticosteroids are the first-line drugs for the treatment of uveitis.The cornbined immunomodulatory agents of cyclosporine,mycophenolate mofetile,azathioprine or cyclophosphamide are helpful for the treatment of severe or refractory uveitis.The new bidogic agents,tumor necrosis factor inhibitors,interferon α or the interleukin-2 receptor antagonists,are also helpful for certain types of refractory uveitis.Intravitreal steroids injection or vitrectomy would be beneficial for specific types of uveitis and their complications.The advances of uveitis treatment in recent years are reviewed.

  19. 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

  20. Perception of the usefulness of drug/gene pairs and barriers for pharmacogenomics in Latin America.

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    Quinones, Luis Abel; Lavanderos, Maria Alejandra; Cayun, Juan Pablo; Garcia-Martin, Elena; Agundez, Jose Augusto; Caceres, Dante Daniel; Roco, Angela Margarita; Morales, Jorge E; Herrera, Luisa; Encina, Gonzalo; Isaza, Carlos Alberto; Redal, Maria Ana; Larovere, Laura; Soria, Nestor Walter; Eslava-Schmalbach, Javier; Castaneda-Hernandez, Gilberto; Lopez-Cortes, Andres; Magno, Luiz Alexandre; Lopez, Marisol; Chiurillo, Miguel Angel; Rodeiro, Idania; Castro de Guerra, Dinorah; Teran, Enrique; Estevez-Carrizo, Francisco; Lares-Assef, Ismael

    2014-02-01

    Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.

  1. Celiac disease (CD, ulcerative colitis (UC, and primary sclerosing cholangitis (PSC in one patient: a family study Enfermedad celiaca (EC, colitis ulcerosa (CU y colangitis esclerosante primaria (CEP asociadas en el mismo paciente: estudio familiar

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    V. Cadahía

    2005-12-01

    Full Text Available We discuss the case of a 17-year-old male who at the age of 7 was diagnosed with celiac disease (CD together with ulcerative colitis (UC and primary sclerosing cholangitis (PSC. The patient was treated with gluten-free diet and immunosuppressive drugs (azathioprine, and currently remains asymptomatic. The patient's younger, 12-year-old sister was diagnosed with CD when she was 1.5 years old, and at 7 years she developed type-I diabetes mellitus, which was difficult to control. A family study was made, and both parents were found to be affected with silent CD. All were DQ2 (+. In relation to the case and family study, we provide a series of comments related to CD and its complications.Presentamos el caso de un varón de 17 años, que a la edad de 7 años fue diagnosticado de enfermedad celiaca (EC junto con una colitis ulcerosa (CU y una colangitis esclerosante primaria (CEP asociadas. Fue tratado con DSG e inmuno-supresores tipo azatioprina y se encuentra asintomático en la actualidad. Su hermana menor de 12 años, fue diagnosticada de EC cuando tenía 1,5 años y a los 7 años desarrolló una DM tipo 1 de difícil control. Se realizó un estudio familiar y ambos padres están afectos de una EC silente. Todos ellos son DQ2 (+. A propósito del caso y estudio familiar, se hacen una serie de consideraciones sobre la enfermedad celiaca y el desarrollo de complicaciones.

  2. Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure.

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    Vereerstraeten, P; Wissing, M; De Pauw, L; Abramowicz, D; Kinnaert, P

    1999-04-01

    The aim of the present retrospective study was to uncover the factor(s) responsible for the poor outcome of cadaver kidney grafts from female donors in male recipients. The 741 transplantations performed at our center from August 1983 to September 1997 were distributed into four groups according to recipient and donor gender: female donor to female recipient (F to F: n = 117), male donor to female recipient (M to F: n = 172), female donor to male recipient (F to M: n = 170), and male donor to male recipient (M to M: n = 282). All the patients received immunosuppressive therapy based on corticosteroids and cyclosporine, associated or not with either azathioprine or prophylactic anti-lymphocyte globulin. Overall graft survival was lower in the F to M group than in the three other groups (p = 0.009). Failures due to rejection were more frequent during the 1st post-transplant trimester in female than in male donor grafts, irrespective of recipient gender (p = 0.025). All failures due to technical problems occurred during the first 3 months post-transplantation: they were more frequent in the F to M group than in the three other groups (p = 0.040): this could be related to the older age of the donors in the former group. After the first post-transplant year, failures due to causes other than rejection remained low in the F to F group but increased steadily in the three other groups (p = 0.007). Specific survival rates were not correlated with the time-evolution of mean serum creatinine values, daily doses and trough levels of cyclosporine in the four groups of grafts. In conclusion, the poor outcome of F to M grafts results from combined immunologic and technical factors exerting their effects early in the course of transplantation. PMID:10202615

  3. OKT3 serum levels as a guide for prophylactic therapy: a pilot study in kidney transplant recipients.

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    Abramowicz, D; Goldman, M; Mat, O; Estermans, G; Crusiaux, A; Vanherweghem, J L; De Pauw, L; Kinnaert, P; Vereerstraeten, P

    1994-07-01

    The use of OKT3 as prophylaxis in renal transplantation results in a reduced incidence of graft rejection and appears to have beneficial effects on long-term kidney graft survival. However, we and others have observed that patients still experience rejection during the period of OKT3 prophylaxis given at the regular 5 mg/day dose. Many of these patients had no circulating CD3+ cells at the time of rejection, but their OKT3 serum levels were distinctly low (< 500 ng/ml). This led us to adjust OKT3 doses (5 or 10 mg) daily, according to the patients' OKT3 levels, in order to maintain an OKT3 concentration of around 1000 ng/ml. In addition, patients were randomized to receive either 5 mg (group 1, n = 15) or 10 ng (group 2, n = 14) OKT3 as the initial three doses. Concomitant immunosuppression consisted of azathioprine and steroids, with the introduction of cyclosporin A on day 11. Patient survival was 100% after 3 months of follow-up. The intensity of OKT3 first-dose reactions was similar in both groups. Intragraft thrombosis, initially observed in a previous group of patients who received a fixed 10 mg/day OKT3 prophylaxis, occurred in three patients in group 1 and resulted in two graft losses. The cumulative OKT3 dose was similar in both groups (mean +/- SEM 98 +/- 2 mg in group 1 vs 102 +/- 3 mg in group 2) and higher than the 70 mg usually administered. Group 2 patients had higher OKT3 serum levels during the first 4 days of therapy. No correlation could be found between patient weight and cumulative OKT3 dose (r = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7916925

  4. The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation--a single-center, prospective, randomized study.

    Science.gov (United States)

    Abramowicz, D; Goldman, M; De Pauw, L; Vanherweghem, J L; Kinnaert, P; Vereerstraeten, P

    1992-09-01

    We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n = 56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n = 52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P less than 0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P less than 0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P less than 0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P = 0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P = 0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation. PMID:1412723

  5. Patient-reported outcome measures in a population of medically indigent patients with systemic lupus erythematosus in Puerto Rico

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    Rodríguez-Rivera, Diana V; Rodríguez-Navedo, Yerania; Nieves-Plaza, Mariely; Vilá, Luis M

    2016-01-01

    Objective: To determine patient-reported outcomes measures in indigent patients with systemic lupus erythematosus receiving their healthcare through the Puerto Rico government managed care system and compare these measures with non-indigent patients treated in a private fee-for-service setting. Methods: A cross-sectional study was conducted in a cohort of 98 Puerto Ricans with systemic lupus erythematosus. Patients from the public group (n = 40) were treated in a university-based specialized systemic lupus erythematosus clinic and the private group (n = 58) in a community-based rheumatology practice. Demographic and clinical features and patient-reported outcomes measures per LupusPRO instrument were determined. LupusPRO captures quality-of-life measures in 12 domains. Differences among study groups were examined using chi-square, Fisher’s exact, t-tests, and the Wilcoxon signed-rank test. Results: The mean (standard deviation) age of the study population was 44.9 (12.0) years; 94 (95.9%) were women. Patients in the public setting were younger and were more likely to have renal disease and elevated anti-double-stranded DNA antibodies, and being treated with azathioprine and cyclophosphamide. Patients from the public sector were more likely to have better quality-of-life measures in the LupusPRO domains of pain/vitality and coping. No significant differences were observed for the domains of lupus symptoms, physical health, emotional health, body image, cognition, procreation, lupus medications, desires/goals, social support, and satisfaction with medical care. Conclusion: Despite having a lower socioeconomic status and worse clinical status, systemic lupus erythematosus patients from the public sector had equal or better patient-reported outcomes measures than those treated in the private setting. This favorable outcome may be associated with the comprehensive healthcare received by these patients in a specialized lupus clinic.

  6. 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

  7. Astaxanthin vs placebo on arterial stiffness, oxidative stress and inflammation in renal transplant patients (Xanthin: a randomised controlled trial

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    Robertson Iain K

    2008-12-01

    Full Text Available Abstract Background There is evidence that renal transplant recipients have accelerated atherosclerosis manifest by increased cardiovascular morbidity and mortality. The high incidence of atherosclerosis is, in part, related to increased arterial stiffness, vascular dysfunction, elevated oxidative stress and inflammation associated with immunosuppressive therapy. The dietary supplement astaxanthin has shown promise as an antioxidant and anti-inflammatory therapeutic agent in cardiovascular disease. The aim of this trial is to investigate the effects of astaxanthin supplementation on arterial stiffness, oxidative stress and inflammation in renal transplant patients. Method and Design This is a randomised, placebo controlled clinical trial. A total of 66 renal transplant recipients will be enrolled and allocated to receive either 12 mg/day of astaxanthin or an identical placebo for one-year. Patients will be stratified into four groups according to the type of immunosuppressant therapy they receive: 1 cyclosporine, 2 sirolimus, 3 tacrolimus or 4 prednisolone+/-azathioprine, mycophenolate mofetil or mycophenolate sodium. Primary outcome measures will be changes in 1 arterial stiffness measured by aortic pulse wave velocity (PWV, 2 oxidative stress assessed by plasma isoprostanes and 3 inflammation by plasma pentraxin 3. Secondary outcomes will include changes in vascular function assessed using the brachial artery reactivity (BAR technique, carotid artery intimal medial thickness (CIMT, augmentation index (AIx, left ventricular afterload and additional measures of oxidative stress and inflammation. Patients will undergo these measures at baseline, six and 12 months. Discussion The results of this study will help determine the efficacy of astaxanthin on vascular structure, oxidative stress and inflammation in renal transplant patients. This may lead to a larger intervention trial assessing cardiovascular morbidity and mortality. Trial Registration

  8. Misleading pustular plaques of the lower limbs during Crohn's disease: two case reports

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    Farhi David

    2007-10-01

    Full Text Available Abstract Background Extraintestinal manifestations of Crohn's disease may involve the skin, the eyes, the genital mucosa, and the joints. Dermatoses associated with Crohn's disease include neutrophilic dermatoses, erythema nodosum, granulomatous dermatitis, blistering dermatoses, and non-specific skin manifestations. Cutaneous Crohn's disease is characterized by skin non-caseating epithelioid granulomatas with giant cells, remote from the gastrointestinal tract. We report herein two new cases. Observations On both patients, differential diagnosis of neutrophilic dermatoses and infectious disease were evoked, and antimicrobial agents were introduced in one of them. Given the atypical presentation, the final diagnosis of cutaneous Crohn's disease could only be made with histological examination. In patient 1, the plaques decreased in size and infiltration by more than 75% after 3 weeks of treatment with bethametasone dipropionate 0.05% cream. In patient 2, the plaques decreased by more than 50% after 6 weeks of treatment with prednisolone (45 mg/day and azathioprine (100 mg/day. Discussion Cutaneous Crohn's disease may present as dusky, erythematous, infiltrated, and ulcerated plaques and nodules. Female-to-male sex ratio is about 2, and the mean age at onset is 35. Recurrently, the hypothesis of a skin mycobacterial or fungal infection greatly delays proper treatment. Rarity of cutaneous Crohn's disease hampers therapeutic assessment in controlled trials. Thus, available literature is limited to case reports and sparse small series, with contradictory results. These reports are subject to publication bias, and no definite evidence-based recommendations can be made on the most adequate therapeutic strategy.

  9. 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.

  10. Eosinophilic granulomatosis with polyangiitis: an overview

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    Andrea eGioffredi

    2014-11-01

    Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA is a multisystemic disorder, belonging to the small vessel ANCA-associated vasculitis, defined as a eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium-sized vessels, associated with asthma and eosinophilia. EGPA pathogenesis is not well known: HLA-DRB1*04 and *07, HLA-DRB4 and IL10.2 haplotype of the IL-10 promoter gene are the most studied genetic determinants. Among the acquired pathogenetic factors, the exposure to different allergens, infections, vaccinations, drugs and silica exposure have been involved.Eosinophils are the most characteristic cells in EGPA and different studies have demonstrated their role as effector and immunoregulatory cells.EGPA is considered a disease with a prevalent activation of the Th2 cellular-mediated inflammatory response but also humoral immunity plays an important role. A link between B and T inflammatory responses may explain different disease features. EGPA typically develops into three sequential phases: the allergic phase, distinguished by the occurrence of asthma, allergic rhinitis and sinusitis, the eosinophilic phase, in which the main pathological finding is the eosinophilic organ infiltrations (e.g. lungs, heart and gastrointestinal system and the vasculitic phase, characterized by purpura, peripheral neuropathy and constitutional symptoms.ANCA (especially pANCA anti-MPO are present in 40-60% of the patients. An elevation of IgG4 is frequently found. Corticosteroids and cyclophosphamide are classically used for remission induction, while azathioprine and methotrexate are the therapeutic options for remission maintenance. B-cell depletion with rituximab has shown promising results for remission induction.

  11. Neuromyelitis Optica (Devic's Syndrome): an Appraisal.

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    Crout, Teresa M; Parks, Laura P; Majithia, Vikas

    2016-08-01

    Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD), previously known as Devic's syndrome, are a group of inflammatory disorders of the central nervous system (CNS) characterized by severe, immune-mediated demyelination and axonal damage, predominantly targeting optic nerves and the spinal cord typically associated with a disease-specific serum NMO-IgG antibody that selectively binds aquaporin-4 (AQP4). The classic and best-defined features of NMOSD include acute attacks of bilateral or rapidly sequential optic neuritis (leading to visual loss) or transverse myelitis (often causing limb weakness and bladder dysfunction) or both with a typically relapsing course. The diagnosis of NMO/NMOSD requires a consistent history and examination with typical clinical presentations, findings on spinal cord neuroimaging with MRI, cerebrospinal fluid analysis along with determination of AQP4-IgG serum autoantibody status, and exclusion of other disorders. Two major advances in this field has been the development of diagnostic criteria and treatment recommendations. Consensus diagnostic criteria have been established and were recently revised and published in 2015, enhancing the ability to make a diagnosis and appropriately evaluate these disorders. Expert recommendations and uncontrolled trials form the basis of treatment guidelines. All patients with suspected NMOSD should be treated for acute attacks as soon as possible with high-dose intravenous methylprednisolone -1 gram daily for three to five consecutive days and in some cases, plasma exchange should be used. It is recommended that every patient with NMOSD be started on an immunosuppressive agent, such as, azathioprine, methotrexate, or mycophenolate and in some cases, rituximab, soon after the acute attack and usually be treated for about 5 years after the attack. These advances have helped improve the prognosis and outcome in these disorders. PMID:27402111

  12. Inflammatory bowel disease in India - Past, present and future.

    Science.gov (United States)

    Ray, Gautam

    2016-09-28

    There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of "hygiene hypothesis" is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn's disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease

  13. A non-BRICHOS surfactant protein c mutation disrupts epithelial cell function and intercellular signaling

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    Beers Michael F

    2010-11-01

    Full Text Available Abstract Background Heterozygous mutations of SFTPC, the gene encoding surfactant protein C (SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. The most frequent SFTPC mutation in ILD patients leads to a threonine for isoleucine substitution at position 73 (I73T of the SP-C preprotein (proSP-C, however little is known about the cellular consequences of SP-CI73T expression. Results To address this, we stably expressed SP-CI73T in cultured MLE-12 alveolar epithelial cells. This resulted in increased intracellular accumulation of proSP-C processing intermediates, which matched proSP-C species recovered in bronchial lavage fluid from patients with this mutation. Exposure of SP-CI73T cells to drugs currently used empirically in ILD therapy, cyclophosphamide, azathioprine, hydroxychloroquine or methylprednisolone, enhanced expression of the chaperones HSP90, HSP70, calreticulin and calnexin. SP-CI73T mutants had decreased intracellular phosphatidylcholine level (PC and increased lyso-PC level without appreciable changes of other phospholipids. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CI73T cells secreted into the medium soluble factors that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine influence of SP-CI73T on neighboring cells in the alveolar space. Conclusion We show that I73T mutation leads to impaired processing of proSP-C in alveolar type II cells, alters their stress tolerance and surfactant lipid composition, and activates cells of the immune system. In addition, we show that some of the mentioned cellular aspects behind the disease can be modulated by application of pharmaceutical drugs commonly applied in the ILD therapy.

  14. Urticarial vasculitis in northern Spain: clinical study of 21 cases.

    Science.gov (United States)

    Loricera, Javier; Calvo-Río, Vanesa; Mata, Cristina; Ortiz-Sanjuán, Francisco; González-López, Marcos A; Alvarez, Lino; González-Vela, M Carmen; Armesto, Susana; Fernández-Llaca, Héctor; Rueda-Gotor, Javier; González-Gay, Miguel A; Blanco, Ricardo

    2014-01-01

    Urticarial vasculitis (UV) is a subset of cutaneous vasculitis (CV), characterized clinically by urticarial skin lesions of more than 24 hours' duration and histologically by leukocytoclastic vasculitis. We assessed the frequency, clinical features, treatment, and outcome of a series of patients with UV. We conducted a retrospective study of patients with UV included in a large series of unselected patients with CV from a university hospital. Of 766 patients with CV, UV was diagnosed in 21 (2.7%; 9 male and 12 female patients; median age, 35 yr; range, 1-78 yr; interquartile range, 5-54 yr). Eight of the 21 cases were aged younger than 20 years old. Potential precipitating factors were upper respiratory tract infections and drugs (penicillin) (n = 4; in all cases in patients aged urticarial lesions, other features such as palpable purpura (n = 7), arthralgia and/or arthritis (n = 13), abdominal pain (n = 2), nephropathy (n = 2), and peripheral neuropathy (n = 1) were observed. Hypocomplementemia (low C4) with low C1q was disclosed in 2 patients. Other abnormal laboratory findings were leukocytosis (n = 7), increased erythrocyte sedimentation rate (n = 6), anemia (n = 4), and antinuclear antibody positivity (n = 2). Treatment included corticosteroids (n = 12), antihistaminic drugs (n = 6), chloroquine (n = 4), nonsteroidal antiinflammatory drugs (n = 3), colchicine (n = 2), and azathioprine (n = 1). After a median follow-up of 10 months (interquartile range, 2-38 mo) recurrences were observed in 4 patients. Apart from 1 patient who died because of an underlying malignancy, the outcome was good with full recovery in the remaining patients. In conclusion, our results indicate that UV is rare but not exceptional. In children UV is often preceded by an upper respiratory tract infection. Urticarial lesions and joint manifestations are the most frequent clinical manifestation. Low complement serum levels are observed in a minority of cases. The prognosis is generally good

  15. Urticarial vasculitis.

    Science.gov (United States)

    Venzor, Joe; Lee, Wai L; Huston, David P

    2002-10-01

    Urticarial vasculitis is a clinico-pathologic entity typified by recurrent episodes of urticaria that have the histopathologic features of leukocytoclastic vasculitis. The cutaneous features may include painful, burning or pruritic skin lesions, the persistence of individual lesions greater than 24 hours, palpable purpura, pronounced central clearing of lesions, and residual hyperpigmentation following resolution. However, because clinical characteristics of urticarial vasculitis may overlap with those of allergic urticaria, confirmation of the diagnosis requires a lesional skin biopsy. This condition is idiopathic in many patients but can also occur in the context of autoimmune disorders, infections, drug reactions, or as a paraneoplastic syndrome. In idiopathic urticarial vasculitis common laboratory findings are an elevation of erythrocyte sedimentation rate and reduction of serum complement. An association between urticarial vasculitis and systemic lupus erythematosus has been hypothesized as some clinical manifestations of disease overlap and C1q autoantibodies may be present in both diseases. Normo-complementemic patients usually have minimal or no systemic involvement and often have a better prognosis. On-the-other-hand, hypocomplementemic patients have the propensity to have more severe multi-organ involvement. Response to treatment is variable and a wide variety of therapeutic agents may be efficacious. Initial recommendations for treatment of urticarial vasculitis manifest only as non-necrotizing skin lesions include antihistamines, dapsone, colchicine, hydroxychloroquine or indomethacin, but corticosteroids are often required. With necrotizing skin lesions or visceral involvement, corticosteroids are regularly indicated. Cases of severe corticosteroid resistant urticarial vasculitis or where corticosteroid morbidity is evident [table: see text] may require treatment with other immunosuppressive agents such as azathioprine, cyclophosphamide, or

  16. Cutaneous hyalohyphomycosis due to Parengyodontium album gen. et comb. nov.

    Science.gov (United States)

    Tsang, Chi-Ching; Chan, Jasper F W; Pong, Wai-Mei; Chen, Jonathan H K; Ngan, Antonio H Y; Cheung, Mei; Lai, Christopher K C; Tsang, Dominic N C; Lau, Susanna K P; Woo, Patrick C Y

    2016-10-01

    "Engyodontium album" is an environmental saprobic mould and an emerging opportunistic pathogen able to cause both superficial and systemic infections. In this study, we isolated a mould from the skin lesion biopsy specimen of the right shin in a patient who received renal transplantation for end-stage renal failure with prednisolone, tacrolimus, and azathioprine immunosuppressant therapy. Histology of the skin biopsy showed mild squamous hyperplasia and neutrophilic infiltrate in the epidermis, active chronic inflammation in the dermis, and fat necrosis in the subcutis, with numerous fungal elements within the serum crusts. On Sabouraud glucose agar, the fungus grew as white, cobweb-like, floccose colonies. Microscopically, conidiogenous cells were arranged in whorls of one to seven at wide angles, with zigzag-shaped terminal fertile regions and smooth, hyaline, oval, apiculate conidia. DNA sequencing showed the mould isolate belonged to "E. album" but matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) failed to identify the isolate. Phylogenetic analyses based on the internal transcribed spacer region, 28S nuclear ribosomal DNA, and β-tubulin gene and MALDI-TOF MS coupled with hierarchical cluster analysis showed that "E. album" is distantly related to other Engyodontium species and should be transferred to a novel genus within the family Cordycipitaceae, for which the name Parengyodontium album gen. et comb. nov. is proposed. Three potential cryptic species within this species complex were also revealed. Antifungal susceptibility testing showed posaconazole and voriconazole had high activities against all clinical P. album isolates and may be better drug options for treating P. album infections. PMID:27161787

  17. Clinical features and management of Crohn's disease in Chinese patients

    Institute of Scientific and Technical Information of China (English)

    郑家驹; 史晓华; 褚行琦; 贾黎明; 王风鸣

    2004-01-01

    Background An increasing incidence of Crohn' s disease has been found in China in recent years.Our study has been focused on evaluating the diversity of the clinical manifestations of Crohn' s disease in order to improve early diagnostic accuracy and therapeutic efficacy.Methods Thirty patients with active Crohn's disease were enrolled and their clinical data, including diagnostic and therapeutic results, were analyzed. Endoscopy combined with histological examination of biopsy specimens provided characteristic features of the disease. Transabdominal bowel sonography (TABS) was used for detecting intestinal complications. Nutritional supportive therapy was given to 20 subjects with active cases of the disease.Results Most patients were young adults with a higher proportion of females to males (ratio: 1.14:1). The disease affects any segment or a combination of segments along with the alimentary tract(from the mouth to the anus). In this study, the colon and small bowel were the major sites involved.Recurrent episodes of abdominal pain in the right lower quadrant and watery diarrhea were the most common symptoms. Granulomas were identifiable in nearly one-third (30.8%) of all biopsy specimens. In moderate cases of the disease, remission was achieved more quickly through the use of oral prednisone therapy than with SASP or 5-ASA. Beneficial effects on the host' s nutritional status were observed. Immunosuppressives were used on an individual basis and showed variable therapeutic effects. Sixteen patients had surgery due to intestinal obstruction or failure to respond to drug therapies. Rapid improvement after surgery was reported. Conclusion Endoscopy (with biopsy) and TABS were both crucial procedures for diagnosis. SASP(or 5-ASA) and prednisone were effective as inductive therapies. Azathioprine has demonstrable benefits after induction therapy with prednisone. Surgery, as an alternative treatment, provided another effective choice in selected patients.

  18. Morvan Syndrome

    Science.gov (United States)

    Maskery, Mark; Chhetri, Suresh K.; Dayanandan, Rejith; Gall, Claire

    2016-01-01

    A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management. PMID:26740856

  19. Current trends in the management of ocular symptoms in Adamantiades-Behçet’s disease

    Directory of Open Access Journals (Sweden)

    Fouad R Zakka

    2009-10-01

    Full Text Available Fouad R Zakka,1 Peter Y Chang,1 Gian P Giuliari,1 C Stephen Foster1,21Massachusetts Eye Research and Surgery institution (MERSI, Cambridge, Massachusetts, USA; 2Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USAAbstract: Adamantiades-Behçet’s disease (ABD is a multisystemic vasculitic disease. It is most prevalent in the Eastern Mediterranean countries and the Eastern region of Asia. Its effect on the eye can range from mild to debilitating, resulting in total blindness. A necrotizing and obliterative vasculitis affects both arteries and veins of organs. Recurrent attacks of uveitis, oral aphthous ulcers, skin lesions, and genital ulcers are common. Topical and systemic corticosteroids have been the mainstay in the treatment of ocular inflammation for many years; however, due to the several known side effects of corticosteroids and thanks to scientific advances, more novel approaches to ABD treatment have been emerging. Antimetabolites such as methotrexate and azathioprine have been utilized with the latter showing positive results. Chlorambucil has been utilized effectively for ocular manifestations of ABD. Interferon alpha has shown encouraging results in the management of refractory ocular inflammation associated with ABD, either alone or in combination with other immunosuppressive agents. Surgical interventions to deal with complications from ABD can be safely done if adequate control of inflammation is achieved peri-operatively. Early detection and aggressive treatment, when needed, have proven to be essential in the management of this relentlessly explosive disease.Keywords: Adamantiades-Behçet’s disease, Behçet’s disease, ocular inflammation, uveitis, immunomodulatory therapy, immunosuppressive therapy

  20. Tuberculosis in renal transplant patients

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    Flávio Jota de Paula

    1987-10-01

    Full Text Available Tuberculosis (TB was diagnosed in 25 of 466 patients who underwent renal transplant over a period of 15 years. TB developed from 1 month to 9 years post-transplant. In 56% of the cases the onset was within the first post-transplant year. TB affected several isolated or combined organs. Pulmonary involvement was present in 76% of cases, either as isolated pleuro-pulmonary (56% or associated with other sites (20%. The non-pulmonary sites were: skin, joints, tests, urinary tract, central nervous system and lymphonodules. The diagnosis was confirmed by biopsy in 64% of the cases, by identification of tubercle bacilli in 24% and only at necropsy in 12% Biopsy specimens could be classified in three histological forms: exudative, that occurred in early onset and more severe cases granulomatous in late onset and benign cases; and mixed in intermediate cases. Azathioprine dosages were similar along post-transplant time periods in TB patients and in the control groups; and in TB patients who were cured and who died. The number of steroid treated rejection crises was greater in TB than in the control group. Prednisone doses were higher and the number of rejection crises was greater in TB patients who died than in those who were cured. Fifteen patients were cured and ten died, two of them of causes unrelated to TB. Six of the eight TB-related deaths occurred in the first 6 post-transplant months. The outcome was poor in patients in whom TB arose early in post-transplant period and where the exudative or mixed forms were present; whereas the prognosis was good in patients with late onset and granulomatous form of TB. In one patient TB was transmitted by the allograft.

  1. Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1992-10-01

    The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality.

  2. Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactation.

    Science.gov (United States)

    Levy, Roger A; de Jesús, Guilherme R; de Jesús, Nilson R; Klumb, Evandro M

    2016-10-01

    The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be

  3. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS).

    Science.gov (United States)

    Trebst, Corinna; Jarius, Sven; Berthele, Achim; Paul, Friedemann; Schippling, Sven; Wildemann, Brigitte; Borisow, Nadja; Kleiter, Ingo; Aktas, Orhan; Kümpfel, Tania

    2014-01-01

    Neuromyelitis optica (NMO, Devic's syndrome), long considered a clinical variant of multiple sclerosis, is now regarded as a distinct disease entity. Major progress has been made in the diagnosis and treatment of NMO since aquaporin-4 antibodies (AQP4-Ab; also termed NMO-IgG) were first described in 2004. In this review, the Neuromyelitis Optica Study Group (NEMOS) summarizes recently obtained knowledge on NMO and highlights new developments in its diagnosis and treatment, based on current guidelines, the published literature and expert discussion at regular NEMOS meetings. Testing of AQP4-Ab is essential and is the most important test in the diagnostic work-up of suspected NMO, and helps to distinguish NMO from other autoimmune diseases. Furthermore, AQP4-Ab testing has expanded our knowledge of the clinical presentation of NMO spectrum disorders (NMOSD). In addition, imaging techniques, particularly magnetic resonance imaging of the brain and spinal cord, are obligatory in the diagnostic workup. It is important to note that brain lesions in NMO and NMOSD are not uncommon, do not rule out the diagnosis, and show characteristic patterns. Other imaging modalities such as optical coherence tomography are proposed as useful tools in the assessment of retinal damage. Therapy of NMO should be initiated early. Azathioprine and rituximab are suggested as first-line treatments, the latter being increasingly regarded as an established therapy with long-term efficacy and an acceptable safety profile in NMO patients. Other immunosuppressive drugs, such as methotrexate, mycophenolate mofetil and mitoxantrone, are recommended as second-line treatments. Promising new therapies are emerging in the form of anti-IL6 receptor, anti-complement or anti-AQP4-Ab biologicals.

  4. Dietary immunosuppressants do not enhance UV-induced skin carcinogenesis, and reveal discordance between p53-mutant early clones and carcinomas.

    Science.gov (United States)

    Voskamp, Pieter; Bodmann, Carolien A; Koehl, Gudrun E; Rebel, Heggert G; Van Olderen, Marjolein G E; Gaumann, Andreas; El Ghalbzouri, Abdoel; Tensen, Cornelis P; Bavinck, Jan N Bouwes; Willemze, Rein; Geissler, Edward K; De Gruijl, Frank R

    2013-02-01

    Immunosuppressive drugs are thought to cause the dramatically increased risk of carcinomas in sun-exposed skin of organ transplant recipients. These drugs differ in local effects on skin. We investigated whether this local impact is predictive of skin cancer risk and may thus provide guidance on minimizing the risk. Immunosuppressants (azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, and rapamycin) were assessed on altering the UV induction of apoptosis in human skin models and of p53 mutant cell clones (putative tumor precursors) and ensuing skin carcinomas (with mutant p53) in the skin of hairless mice. Rapamycin was found to increase apoptosis (three-fold), whereas cyclosporine decreased apoptosis (three-fold). Correspondingly, a 1.5- to five-fold reduction (P = 0.07) or a two- to three-fold increase (P UV-exposed skin of mice that had been fed rapamycin or cyclosporine, respectively. Deep sequencing showed, however, that the allelic frequency (∼5%) of the hotspot mutations in p53 (codons 270 and 275) remained unaffected. The majority of cells with mutated p53 seemed not to overexpress the mutated protein. Unexpectedly, none of the immunosuppressants admixed in high dosages to the diet accelerated tumor development, and cyclosporine even delayed tumor onset by approximately 15% (P < 0.01). Thus, in contrast to earlier findings, the frequency of p53-mutant cells was not predictive of the incidence of skin carcinoma. Moreover, the lack of any accelerative effect on tumor development suggests that immunosuppressive medication is not the sole cause of the dramatic increase in skin cancer risk in organ transplant recipients.

  5. Short-tem Post Renal Trasplant Follow-up at Madinah Al Munawarah

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    Bernieh Bassam

    1999-01-01

    Full Text Available We reviewed the records of the renal transplant patients followed at our hospital to determine short-term outcome and complications. Sixty-five renal transplant patients, follow-up for two years were included in this study. Of these patients 40 (61.5% were males, 33 (50.7% were Saudis with mean age of 37.2 ± 11.7 years. Donors were living related (LRD in 23 (35%, living non-related (LNRD in 27 (42% and cadaveric (CAD in 15 (23%. Thirty-two transplants were carried out at Medinah, 21 in India and the rest in other centers inside Saudi Arabia. Immunosuppression was based on a triple therapy (Cyclosporin, Azathioprine, and Prednisone. At two years, 52 (80% patients were alive, with functioning graft in 31 (58%. Causes of death among 13 patients (11 LNRD & 2 CAD were infections in 7 (54%, immediate post transplant in three (22.7%, acute myocardial infarction in two (15.7%, CVA in one (7.6%. Complications encountered were acute rejection (23 episodes in 18 923.6% patients, infections in 19 (25%, chronic rejection in 16 (21.5%, surgical in 13 917.1%, diabetes mellitus in 5 (6.5% primary non-function in three (3.8% and Kaposi Sarcoma in two (2.4%. Twenty-six (81.25% out of 32 transplants performed in Madinah were functioning, four (12.5% patients returned to dialysis and two (6.25% patients died. Among the 21 transplants done in India 11 (52% patients died, six (28.6% returned to dialysis, and four (19.4% had function deteriorated in all patients. We conclude that despite limitations, results of renal transplantation carried out at Madinah are encouraging on short-term basis. Live related transplant has a very good outcome, while commercial transplantation carries poor prognosis.

  6. Newer therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Kuitwaard, Krista; van Doorn, Pieter A

    2009-05-29

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder with variable symptoms and severity that can be difficult to diagnose. Intravenous immunoglobulin, plasma exchange and corticosteroids have all been proven to be beneficial in randomized controlled trials, although the proof for corticosteroids is less clear. Although these treatments are likely to be similar in efficacy, they differ in terms of their cost, availability and adverse effects. These characteristics should be taken into account when deciding which treatment to offer a patient. If there is no response to the first treatment option, one of the other treatments should be tried. Patients with a pure motor CIDP may deteriorate after corticosteroid treatment. Some patients do not respond or become refractory or intolerant to these conventional treatments. Those who become unresponsive to therapy should be checked again for the appearance of a monoclonal protein or other signs of malignancy. Over the years, small non-randomized studies have reported possible beneficial effects of various immunosuppressive agents. A Cochrane review concluded that currently there is insufficient evidence to decide whether these immunosuppressive drugs are beneficial in CIDP. When giving immunosuppressive drugs, one should be aware that some might even cause demyelinating disease. It is difficult to prove beneficial effects of these newer treatments since they have only been used in small groups of patients, who are refractory to other treatments, and often in combination with other treatments. CIDP patients can deteriorate during or after infections or improve spontaneously, making it more difficult to judge treatment efficacy. Various treatments for CIDP are described such as azathioprine, ciclosporin, cyclophosphamide, interferons, methotrexate, mycophenolate mofetil, rituximab and etanercept. An overview of these newer treatments, their mode of action, adverse effects and

  7. Does the chronic inflammatory demyelinating polyradiculoneuropathy due to secondary cause differ from primary?

    Directory of Open Access Journals (Sweden)

    Vaibhav Wadwekar

    2011-01-01

    Full Text Available Background: The clinical presentation, neurophysiological findings, and outcome may vary between primary and secondary chronic inflammatory demyelinating polyradiculopathy (CIDP. Objective: To compare clinical and electrodiagnostic features of primary and secondary CIDP. Setting: Tertiary care teaching referral hospital. Materials and Methods: The CIDP patients who were diagnosed as per European Federation of Neurological Societies/Peripheral Nerve Society criteria were included and subjected to detailed history and examinations. The clinical disability was graded on a 0-10 scale. Neurophysiology included motor and sensory nerve conductions and F wave studies of all four limbs. Based on investigations for underlying diseases, the patients were categorized into primary or secondary CIDP. Prednisolone was prescribed in all and azathioprine added in resistant cases. The secondary CIDP group received specific treatment in addition. The outcome was assessed at 3 months, 6 months, and last follow-up. Results: A total of 65 patients aged 17 to 72 years were included and 20 were females. Twenty-five patients had secondary CIDP and include diabetes mellitus (16, POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (4, monoclonal gammopathy of undetermined significance (2, myeloma (1, lymphoma (1, and malignancy (1. The secondary CIDP patients were older (48.35 vs 41.0 years, had less relapsing remitting (0 vs 6 and more frequent dysautonomia (7 vs 1. The demyelinating features were more marked in primary CIDP group and had better outcome compared with secondary CIDP. Conclusions: Of the total patients with CIDP, 38.5% of patients had secondary CIDP which was associated with progressive course, less demyelinating features, and worse prognosis.

  8. Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactation.

    Science.gov (United States)

    Levy, Roger A; de Jesús, Guilherme R; de Jesús, Nilson R; Klumb, Evandro M

    2016-10-01

    The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be

  9. Chronic lupus peritonitis is characterized by the ascites with a large content of interleukin-6.

    Science.gov (United States)

    Watanabe, Ryu; Fujii, Hiroshi; Kamogawa, Yukiko; Nakamura, Kyohei; Shirai, Tsuyoshi; Ishii, Tomonori; Harigae, Hideo

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease and can cause multi-organ damage. Peritoneal involvement, also called lupus peritonitis, is a rare but sometimes fatal manifestation. Deposition of immune complexes consisting of immunoglobulin G and complement is considered to be involved in the pathogenesis of lupus peritonitis; however, it remains unknown whether inflammatory cytokines contribute to the pathology of this manifestation. Here we present two patients with treatment-resistant lupus peritonitis: a 37-year-old woman with a 26-year history of SLE who had been treated with prednisolone and cyclophosphamide followed by azathioprine and a 65-year-old woman with a 33-year history of SLE who had been treated with prednisolone alone. Both patients were admitted to our department because of abdominal distention. Computed tomography scans showed massive ascites. Ascitic fluid examinations of both patients showed leukocytosis with no evidence of malignancy or infection. After eliminating other causes for ascites, they were diagnosed with lupus peritonitis. Despite the intensified immunosuppressive therapy, they died of uncontrolled peritonitis several months after admission. Examinations of the ascites at admission also revealed a large content of interleukin (IL)-6, compared with other inflammatory cytokines, IL-1β and tumor necrosis factor-α. In fact, the ascitic IL-6 levels of these two patients were 12,389 pg/mL and 5,486 pg/mL, much higher than their serum IL-6 levels of 36 pg/mL and 140 pg/mL, respectively. We therefore suggest that IL-6 may contribute to the pathogenesis of lupus peritonitis and that the inhibition of IL-6 signaling may provide a novel therapeutic strategy for lupus peritonitis.

  10. 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

    2016-06-24

    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

  11. 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

  12. Current management of gout in patients unresponsive or allergic to allopurinol.

    Science.gov (United States)

    Bardin, Thomas

    2004-11-01

    azathioprine, which contraindicates the use of allopurinol. PMID:15589427

  13. Mechanism of allopurinol induced TPMT inhibition.

    Science.gov (United States)

    Blaker, P A; Arenas-Hernandez, M; Smith, M A; Shobowale-Bakre, E A; Fairbanks, L; Irving, P M; Sanderson, J D; Marinaki, A M

    2013-08-15

    Up to 1/5 of patients with wildtype thiopurine-S-methyltransferase (TPMT) activity prescribed azathioprine (AZA) or mercaptopurine (MP) demonstrate a skewed drug metabolism in which MP is preferentially methylated to yield methylmercaptopurine (MeMP). This is known as thiopurine hypermethylation and is associated with drug toxicity and treatment non-response. Co-prescription of allopurinol with low dose AZA/MP (25-33%) circumvents this phenotype and leads to a dramatic reduction in methylated metabolites; however, the biochemical mechanism remains unclear. Using intact and lysate red cell models we propose a novel pathway of allopurinol mediated TPMT inhibition, through the production of thioxanthine (TX, 2-hydroxymercaptopurine). In red blood cells pre-incubated with 250 μM MP for 2h prior to the addition of 250 μM TX or an equivalent volume of Earle's balanced salt solution, there was a significant reduction in the concentration of MeMP detected at 4h and 6h in cells exposed to TX (4 h, 1.68, p=0.0005, t-test). TX acts as a direct TPMT inhibitor with an apparent Ki of 0.329 mM. In addition we have confirmed that the mechanism is relevant to in vivo metabolism by demonstrating raised urinary TX levels in patients receiving combination therapy. We conclude that the formation of TX in patients receiving combination therapy with AZA/MP and allopurinol, likely explains the significant reduction of methylated metabolites due to direct TPMT inhibition. PMID:23770457

  14. 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. PMID:15604604

  15. Clinical use of pharmacogenomic tests in 2009.

    Science.gov (United States)

    Sheffield, Leslie J; Phillimore, Hazel E

    2009-05-01

    Pharmacogenomics is a new field where testing an individual can define either a risk status for an adverse event, or the rate of metabolism of a drug. This is achieved by the categorisation of the enzyme activity or documenting genetic polymorphisms of a metabolising enzyme. The best example of risk status assessment is the recent finding that HLA-B typing a person can predict whether they are at risk of a severe skin reaction from the drug abacavir. Those patients showing HLA-B*5701, who are being considered for abacavir therapy, can be prevented from developing potentially toxic epidermal necrosis (TEN) or Stevens-Johnson Syndrome by avoiding abacavir. The evidence for HLA-B typing for allopurinol and carbamazepine has also been described. Most other pharmacogenomic tests are of drug metabolising enzymes, which can either be assessed using "probe" drugs and measuring a ratio of parent drug to metabolite, or, by genetic testing for polymorphisms of the genes. In practice, testing is usually done by molecular testing, but this typically does not detect all polymorphisms. This article briefly reviews the evidence for the utilisation of pharmacogenomics for antidepressant drugs, tamoxifen, codeine, warfarin, azathioprine, clopidogrel, omeprazole, tacrolimus and irinotecan. There are few pharmacogenomics tests being carried out in practice, as there has not been a wide appreciation of their use, and only limited evidence exists for many individual drugs. It is expected that utilisation will increase as more evidence becomes available and there is a wider understanding of the existing evidence by the medical profession. PMID:19565025

  16. Autoimmune hepatitis from the paediatric perspective.

    Science.gov (United States)

    Roberts, Eve A

    2011-11-01

    Autoimmune hepatitis (AIH) is an important entity within the broad spectrum of autoimmune hepatobiliary disease comprised of AIH, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since the 1960s, AIH has been investigated with extensive clinical research aimed at effective therapeutic intervention. It was one of the first liver diseases where treatment was demonstrated to prolong survival. AIH occurs in children, as well as in adults. Its clinical manifestations in children may differ from classic adult AIH. These differences have elucidated certain aspects of AIH and hepatobiliary disease in general. There are two major patterns of AIH: type 1, with anti-smooth muscle antibodies and type 2, with anti-liver/kidney microsomal antibodies. The second type of AIH was first identified in children and is more common in younger patients. AIH often presents as acute disease in children and also in adults: the nomenclature has dropped the allusion to chronicity. Some children who have sclerosing cholangitis present with clinical disease closely resembling AIH; this AIH-like PSC, termed autoimmune sclerosing cholangitis (ASC), is also found in adults. Children with AIH may have identifiable monogenic disorders of immune regulation such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Like adults with AIH, children with AIH usually respond very favourably to immunosuppressive treatment with corticosteroids ± azathioprine. True cures seem to be rare, although many children achieve a stable remission. Nonetheless children with AIH may develop cirrhosis and some require liver transplantation. Early diagnosis and improved treatment strategies may further improve the outlook for children with AIH.

  17. Crohn's disease and acute pancreatitis. A review of literature.

    Science.gov (United States)

    Jasdanwala, Sarfaraz; Babyatsky, Mark

    2015-03-01

    Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.

  18. Comparison of in vitro and in vivo clastogenic potency based on benchmark dose analysis of flow cytometric micronucleus data.

    Science.gov (United States)

    Bemis, Jeffrey C; Wills, John W; Bryce, Steven M; Torous, Dorothea K; Dertinger, Stephen D; Slob, Wout

    2016-05-01

    The application of flow cytometry as a scoring platform for both in vivo and in vitro micronucleus (MN) studies has enabled the efficient generation of high quality datasets suitable for comprehensive assessment of dose-response. Using this information, it is possible to obtain precise estimates of the clastogenic potency of chemicals. We illustrate this by estimating the in vivo and the in vitro potencies of seven model clastogenic agents (melphalan, chlorambucil, thiotepa, 1,3-propane sultone, hydroxyurea, azathioprine and methyl methanesulfonate) by deriving BMDs using freely available BMD software (PROAST). After exposing male rats for 3 days with up to nine dose levels of each individual chemical, peripheral blood samples were collected on Day 4. These chemicals were also evaluated for in vitro MN induction by treating TK6 cells with up to 20 concentrations in quadruplicate. In vitro MN frequencies were determined via flow cytometry using a 96-well plate autosampler. The estimated in vitro and in vivo BMDs were found to correlate to each other. The correlation showed considerable scatter, as may be expected given the complexity of the whole animal model versus the simplicity of the cell culture system. Even so, the existence of the correlation suggests that information on the clastogenic potency of a compound can be derived from either whole animal studies or cell culture-based models of chromosomal damage. We also show that the choice of the benchmark response, i.e. the effect size associated with the BMD, is not essential in establishing the correlation between both systems. Our results support the concept that datasets derived from comprehensive genotoxicity studies can provide quantitative dose-response metrics. Such investigational studies, when supported by additional data, might then contribute directly to product safety investigations, regulatory decision-making and human risk assessment. PMID:26049158

  19. Inflammatory bowel disease in India - Past, present and future.

    Science.gov (United States)

    Ray, Gautam

    2016-09-28

    There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of "hygiene hypothesis" is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn's disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease

  20. Miliary tuberculosis: a severe opportunistic infection in juvenile systemic lupus erythematosus patients

    Directory of Open Access Journals (Sweden)

    Priscilla S. Freire

    2016-06-01

    Full Text Available Abstract Introduction One of the main issues in juvenile systemic lupus erythematosus (JSLE patients is infection, such as tuberculosis (TB. Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5% of them met the American College of Rheumatology classification criteria for SLE. Case reports Four (1.4% of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20 and 5.5 years (range 2-7, respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K was 4 (2-16 and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide. Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide was indicated in the other two TB cases, however they deceased. Discussion Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients.

  1. Drug-Induced Acute Pancreatitis in a Cohort of 328 Patients. A Single-Centre Experience from Australia

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    Savio G Barreto

    2011-11-01

    Full Text Available Context Acute pancreatitis is associated with risk of morbidity and even mortality. Routine prescription drugs have been linked to the causation of acute pancreatitis. Objective To determine the incidence, presentation, course and outcome of drug-induced acute pancreatitis amongst patients admitted to a public hospital. Design/setting A retrospective analysis of patients presenting with acute pancreatitis to the Modbury Hospital, South Australia from January 2006 to April 2011. Main outcome measure Each admission was reviewed within the electronic database for patient details as well as to determine the aetiological factor. In patients with druginduced acute pancreatitis, the WHO Probability Scale was used to evaluate causality relationship. Results Three-hundreds and 28 patients were treated for acute pancreatitis during the study period. Biliary and alcohol-induced acute pancreatitis accounted for 80.8% of cases. Eleven patients (2 male and 9 female patients; median age: 59 years were diagnosed with drug-induced acute pancreatitis. These included 5 cases of codeine-, 2 cases of azathioprine-, and 1 case each of chlorothiazide-, valproic acid-, oestradiol- and rosuvastatin-induced acute pancreatitis. Nine patients had a mild disease while 2 patients had severe acute pancreatitis with a median hospital stay of 4 days. Withdrawal of the drug resulted in cessation of the attacks in all patients over a median follow-up of 24 months. Conclusions Routine prescription drugs, as an aetiological factor, accounted for 3.4% of cases of acute pancreatitis. The disease appeared to be more common in middle-aged women. It is likely that the overall incidence of this entity is under-reported owing to the stringent criteria needed to conclusively determine a causal relationship.

  2. Safety Events in Kidney Transplant Recipients: Results from the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) Trial

    Science.gov (United States)

    Weir, Matthew R.; Gravens-Muller, Lisa; Costa, Nadiesda; Ivanova, Anastasia; Manitpisitkul, Wana; Bostom, Andrew G.; Diamantidis, Clarissa J.

    2015-01-01

    Background Kidney transplant recipients are at increased risk for adverse safety events related to their reduced renal function and many medications. Methods We determined the incidence of adverse safety events based on previously defined Agency for Healthcare and Research Quality (AHRQ) ICD-9 code-derived patient safety indicators (PSI) in the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) trial participants who had a hospitalization stratified by tertiles of estimated glomerular filtration rate. We also examined the frequency of Micromedex defined two precautionary drug-drug interactions, and two medications whose use may be contraindicated due to reduced GFR from the FAVORIT trial Medication Thesaurus at baseline, and annually among 4110 participants. Logistic regression was used to examine the relationship between patient safety events and baseline demographic and clinical variables at a participant level. Event rates were estimated at participant and visit levels. Results Of the 2514 patients with a hospitalization, 978 (38.9%) experienced an AHRQ PSI. Factors which were associated with more common AHRQ PSI included: US location, history of cardiovascular disease or diabetes, and lower tertile of estimated GFR. At a participant level, 2524 of the 4110 participants (61.4%) were taking a CNI and a statin, 378 (9.2%) were taking azathioprine and an ACE inhibitor, 171 (12.9%) were taking a sulfonylurea ), 45 (3.4%) were taking metformin despite a baseline GFR below 40 ml/min/1.73m2. Conclusions We conclude that patient safety events are not uncommon in kidney transplant recipients. Careful monitoring is necessary to prevent adverse outcomes. PMID:25393158

  3. Infliximab for the Treatment of Crohn'S Disease: Review and Indications for Clinical Use in Canada

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    Remo Panaccione

    2001-01-01

    Full Text Available Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. It may affect any portion of the gastrointestinal tract from the mouth to the anus. Symptoms typically include cramping abdominal pain, diarrhea (which may be bloody and nausea. As the severity of the illness worsens, patients may experience constant abdominal pain, vomiting, weight loss and fever. From the perspective of the patient, disease symptoms significantly impair quality of life, and interfere with their work environment and activities of daily living. Unfortunately, there is no cure for Crohn's disease. Patients experience a chronic, relapsing course characterized by recurrent flares of their disease. Conventional medical treatment of Crohn's disease includes the use of non-specific anti-inflammatory drugs (5-aminosalicylic acid agents, prednisone, budesonide, immunosuppressives (6-mercaptopurine, azathioprine, methotrexate and antibiotics. A variable onset of action, incomplete response rates and a significant risk of adverse effects characterize current therapies. Although surgery is frequently used to treat complications or medically refractory disease, postoperative recurrence is a common problem. Infliximab, a murine chimeric monoclonal antibody directed toward tumour necrosis factor-alpha, is a highly effective treatment of active Crohn's disease. In randomized, placebo-controlled clinical trials, 33% of patients treated with infliximab 5 mg/kg achieved remission (Crohn's Disease Activity Index score less than 150, compared with only 4% of those receiving placebo (P<0.001. Additionally, infliximab is the only drug therapy shown to be effective for the treatment of fistulizing Crohn's disease. In studies done to date, infliximab appears to be well tolerated and has a favourable side effect profile.

  4. Dyslipidemia After Kidney Transplantation and Correlation With Cyclosporine Level

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    Hosseini

    2013-06-01

    Full Text Available Background Dyslipidemia after kidney transplantation is a frequent finding and is multifactorial. Immunosuppressive agents such as cyclosporine (CsA can cause hypercholesterolemia. Objectives As there were few reports with conflicting evidence on whether CsA related dyslipidemia is dose related and that CsA monitoring assays (trough level, C0, or two hour post dose level, C2 is a better predictor for dyslipidemia development; hence, the current study, in a large sample size, was designed to answer these questions. 3. Patients and Methods In the current retrospective cross sectional study, 1391 kidney transplant recipients were enrolled. All patients received CsA plus mycophenolatemofetile or azathioprine and prednisolone. Serum creatinine, CsA blood levels and lipid profile were measured after 12-14 h fasting. Mann-Whitney and Kruskal-Wallis, Pearson`s test and logistic regression were used for data analyses. Results Mean age of 1391studied population was 38.7 ± 15 years old. Hypercholesterolemia and hypertriglyceridemia were observed in 58.9% and 86.6%, respectively and they were more significantly detected in cadaveric kidney transplantation. Dyslipidemia had weak correlation with age of recipient, serum creatinine, C0 and C2 levels of CsA. At logistic regression, serum creatinine was the only risk factor for hypercholesterolemia development after kidney transplantation (OR = 1.6, CI 95%: 1.4 -1.8. Conclusions Dyslipidemia is a common finding after kidney transplantation and has no correlation with CsA level. According to conflicting data on the precise effect of different factors in inducing dyslipidemia, prospective large sample size studies should consider better control of dyslipidemia.

  5. Juvenile Myasthenia Gravis: A Report of Three Cases and Literature Review

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    Ünsal Yilmaz

    2014-03-01

    Full Text Available Aim: Juvenile myasthenia gravis accounts for 10% to 15% of all cases and it is even rarer in prepubertal children. Therefore, limited data are available on its presentation, diagnosis, treatment and outcome, particularly in younger children. Early diagnosis is imperative for delaying the progression of the disease, and prevention and adequately management the myasthenic crisis. Presence of acetylcholine receptor antibodies which occur only in half of prepubertal children wih myastenia helps in the diagnosis. Seronegative cases need to be distinguished from congenital forms which may present with similar symptoms. Material and Method: This article presents the initial presentation, clinical course, and 2-year follow-up results of 3 patients with juvenile myasthenia gravis, and reviewes the disease in general and current treatment modalities. Results: The ages at onset were 3, 4 and 7 years. The initial symptom was fluctuating pitosis in all cases. Acetylcholine receptor antibodies were below the normal range in the younger 2 patients, and became positive at 12th months of follow-up with a 2-fold increase. These 2 patients remained symptoms-free with pyridostigmine therapy during the 20-month follow-up period. In the remaining patient who had high antibody titers, symptoms progressed to involve other muscle groups at 10th months of follow-up period while receiving pyridostigmine. After lack of response to prednisolone trial, symptoms improved with azathioprine and monthly intravenous immunoglobulin therapy. Discussion: Juvenile myasthenia gravis in younger children with low acetylcholine receptor antibody titers follows a benign course. Acetylcholine receptor antibodies which were negative at onset, may become positive at 1-year of follow-up. Older children with high antibody titers at onset follow more aggressive disease course needing immunosuppressive therapy.

  6. Myasthenia gravis

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    Massey Janice M

    2007-11-01

    Full Text Available Abstract Myasthenia gravis (MG is a rare, autoimmune neuromuscular junction disorder. Contemporary prevalence rates approach 1/5,000. MG presents with painless, fluctuating, fatigable weakness involving specific muscle groups. Ocular weakness with asymmetric ptosis and binocular diplopia is the most typical initial presentation, while early or isolated oropharyngeal or limb weakness is less common. The course is variable, and most patients with initial ocular weakness develop bulbar or limb weakness within three years of initial symptom onset. MG results from antibody-mediated, T cell-dependent immunologic attack on the endplate region of the postsynaptic membrane. In patients with fatigable muscle weakness, the diagnosis of MG is supported by: 1. pharmacologic testing with edrophonium chloride that elicits unequivocal improvement in strength; 2. electrophysiologic testing with repetitive nerve stimulation (RNS studies and/or single-fiber electromyography (SFEMG that demonstrates a primary postsynaptic neuromuscular junctional disorder; and 3. serologic demonstration of acetylcholine receptor (AChR or muscle-specific tyrosine kinase (MuSK antibodies. Differential diagnosis includes congenital myasthenic syndromes, Lambert Eaton syndrome, botulism, organophosphate intoxication, mitochondrial disorders involving progressive external ophthalmoplegia, acute inflammatory demyelinating polyradiculoneuropathy (AIDP, motor neuron disease, and brainstem ischemia. Treatment must be individualized, and may include symptomatic treatment with cholinesterase inhibitors and immune modulation with corticosteroids, azathioprine, cyclosporine, and mycophenolate mofetil. Rapid, temporary improvement may be achieved for myasthenic crises and exacerbations with plasma exchange (PEX or intravenous immunoglobulin (IVIg. Owing to improved diagnostic testing, immunotherapy, and intensive care, the contemporary prognosis is favorable with less than five percent mortality

  7. Recent advances in the management of distal ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Ioannis; E; Koutroubakis

    2010-01-01

    The most frequent localization of ulcerative colitis(UC) is the distal colon.In treating patients with active distal UC,efficacy and targeting of the drug to the distal colon are key priorities.Oral and rectal 5-aminosalicylic acid(5-ASA) preparations represent the first line therapy of mild-to-moderate distal UC for both induction and maintenance treatment.It has been reported that many UC patients are not adherent to therapy and that noncompliant patients had a 5-fold risk of experiencing a relapse.These findings led to the introduction of oncedaily oral regimens of 5-ASA as better therapeutic options in clinical practice due to improved adherence.New formulations of mesalazine,including the multimatrix delivery system,and mesalazine granules,which allow once-daily administration,have been developed.They have been demonstrated to be efficacious in inducing and maintaining remission in mild-to-moderate distal UC in large clinical trials.However,existing data for distal UC are rather insufficient to make a comparison between new and classical 5-ASA formulations.It seems that the new formulations are at least as effective as classical oral 5-ASA formulations.Other treatment options,in the case that 5-ASA therapy is not effective,include systemic corticosteroids,thiopurines(azathioprine or 6-mercaptopurine),cyclosporine,infliximab and surgery.The combination of a prompt diagnostic work-up,a correct therapeutic approach and an appropriate follow-up schedule is important in the management of patients with distal UC.This approach can shorten the duration of symptoms,induce a prolonged remission,improve patient’s quality of life,and optimize the use of health resources.

  8. Management of patients with end stage pulmonary fibrosis: Challenges, tempations and possibilities

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    Ristić Lidija

    2013-01-01

    Full Text Available Introduction. Pulmonary fibrosis is a heterogeneous group of chronic lung diseases of unclear pathogenesis, with progressive, irreversible development of various forms of fibrotic processes in the lung, whose incidence and mortality rate increases worldwide. Prognostic Evaluation. Some clinical forms have a long, stable phase, some are slowly progressive, and some have a very rapid progression from diagnosis to death. Their clinical course is characterized by acute exacerbations with high mortality. The staging of this disease includes diagnostics of the stable condition, progression and the end stage of disease. This paper presents the diagnostic criteria necessary for the diagnosis of pulmonary fibrosis and its monitoring. The latest research suggests that the decrease in forced vital capacity values by more than 10% during the 24 weeks doubles the risk of death over the next 12 months, and the reduction in the 6-minute walk test by 50 meters increases it four times. Therefore, monitoring of these prognostic parameters is now regarded as the most reliable predictor of death in patients with pulmonary fibrosis. Therapy. This paper also presents the newest recommendations for treatment modalities based on strong evidence. Conclusion. Treatment of pulmonary fibrosis in our conditions includes conventional therapy with corticosteroids as monotherapy or in combination with cyclophosphamide or azathioprine, whereas the management of end-stage patients consists of long-term controlled oxygen therapy, noninvasive and mechanical ventilation. Lung transplantation is considered to be the only therapeutic measure resulting in a significant extension of life. Unfortunately, our health legislation allows lung transplantation only in case of cystic fibrosis and this cannot be done in Serbia but in health centres abroad. Therefore, management in end-stage of disease is reduced to mere palliative care, even at intensive care units.

  9. Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors*

    Science.gov (United States)

    Pinho, André; Gouveia, Miguel; Cardoso, José Carlos; Xavier, Maria Manuel; Vieira, Ricardo; Alves, Rui

    2016-01-01

    Background Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. Objectives To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Methods Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. Results We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Conclusion Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies. PMID:27579740

  10. Inflammatory bowel disease in India - Past, present and future

    Science.gov (United States)

    Ray, Gautam

    2016-01-01

    There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of “hygiene hypothesis” is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn’s disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper

  11. [Recommendations of Czech Rheumatological Society for the treatment of rheumatoid arthritis. Efficacy and treatment strategies].

    Science.gov (United States)

    Becvár, R; Vencovský, J; Nĕmec, P; Suchý, D; Procházková, L; Pavelka, K

    2008-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease of unknown aetiology characterized by presence of chronic symmetric synovitis, which leads to the formation of joint erosions. Generally recommended method for activity assessment of RA is so called Disease Activity Score (DAS). In early RA when low disease activity is present with oligo- or monoarthritis antimalarials are drugs of choice, while sulfasalazine (SAS) is recommended in cases with medium activity without erosions. Initial treatment with methotrexate (MTX) or leflunomide (LEF) should be applied in a very active polyarthritis with a rapid development of erosions. MTX is often combined with other disease modifying drugs (DMARD) and the blockers of tumour necrosis factor alpha (TNF-alpha). LEF is to be administered to the patients in whom the other DMARD are contraindicated or not tolerated. In established RA with oligo- or monoarthritis with permanent low activity SAS is DMARD of choice. In cases with insufficient response and medium activity MTX is used and if it is inefficient LEF or combination of DMARD should be considered. In a very active disease with a rapid evolution of erosions high doses of MTX or LEF are recommended. When extraarticular symptoms of RA are present azathioprine is to be applied and in case of involvement of vital organs cyclophosphamide should be used. When DMARD are failing or contraindicated TNF-alpha blockers are to be applied. When one TNF-alpha blocker is inefficient it should by replaced by another one from the same group or another biological should be used. For indication of biologicals the activity limit is DAS28 5.1 and the decrease of DAS28 more than 1.2 is an efficacy criterion. Nonsteroidal antirheumatic drugs are an important part in the management of RA, and also corticosteroids are often of used in oral or parenteral form. To the complex therapy of RA nonpharmacological means are usually implemented--different physical procedures and various surgeries. PMID

  12. Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs.

    Science.gov (United States)

    Hostutler, Roger A; Luria, Brian J; Johnson, Susan E; Weisbrode, Steven E; Sherding, Robert G; Jaeger, Jordan Q; Guilford, W Grant

    2004-01-01

    Canine histiocytic ulcerative colitis (HUC) is characterized by colonic inflammation with predominantly periodic acid-Schiff (PAS)-positive macrophages. The inflammation results in colonic thickening, ulcerations, and distortion of normal glandular architecture. Resultant clinical signs consist of chronic large bowel diarrhea, tenesmus, and marked weight loss, and the disease frequently results in euthanasia. Conventional therapy consists of some combination of prednisone, azathioprine, sulfasalazine, and metronidazole. Nine dogs (8 Boxers and 1 English Bulldog) with histologic confirmation of HUC were treated with antibiotic therapy (either with enrofloxacin alone or in combination with metronidazole and amoxicillin). Clinical signs, physical examination findings, laboratory abnormalities, and the histologic severity of the disease were evaluated. Four of the 9 dogs had been treated previously with conventional therapy and had failed to respond favorably; then, these dogs were placed on antibiotic therapy (enrofloxacin, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3) and had resolution of clinical signs within 3-12 days. Five dogs were treated solely with antibiotic therapy (enrofloxacin, n = 1; enrofloxacin and metronidazole, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3), and clinical signs resolved in 2-7 days. Repeated biopsy specimens were obtained from 5 dogs after treatment, and all showed marked histologic improvement. The increase in body weight after treatment was statistically significant (P = .01). Three dogs currently are not on any treatment and have had resolution of clinical signs for up to 14 months. These observations suggest that an infectious agent responsive to antibiotics plays an integral role in the clinical manifestation of canine HUC, and they support the use of antibiotics in its treatment.

  13. 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

  14. Systemic therapy of atopic dermatitis in children.

    Science.gov (United States)

    Ricci, Giampaolo; Dondi, Arianna; Patrizi, Annalisa; Masi, Massimo

    2009-01-01

    Atopic dermatitis (AD) is a common disease in childhood that is a serious burden on patients and their families. Most AD is mild and can be managed with the use of emollients and standard therapy consisting of topical corticosteroids or topical calcineurin inhibitors. However, in a subgroup of patients with moderate to severe AD, the disease is recalcitrant to topical therapy and systemic treatments become necessary. Short courses of systemic corticosteroids are often used in clinical practice, but their use is controversial. International guidelines suggest that in the case of acute flare-ups, patients might benefit from a short course of systemic corticosteroids, but long-term use and use in children should be avoided. Ciclosporin is an immunosuppressant agent that acts directly on cells of the immune system, with an inhibitory effect on T cells. When AD cannot be controlled by standard topical therapies, ciclosporin significantly decreases symptom scores, disease extent, pruritus and sleep deprivation, and improves quality of life. The most frequent adverse effects associated with the use of ciclosporin are hypertension and renal dysfunction, but they are usually reversible after drug discontinuation. Ciclosporin has been found to be safely used, effective and well tolerated in children with severe AD. However, studies to assess the long-term effectiveness and safety of ciclosporin in AD are lacking. In patients for whom ciclosporin is not suitable, or when there is a lack of response, alternative drugs should be considered, such as azathioprine or interferon-gamma. Intravenous immunoglobulins and the monoclonal antibody infliximab only have a place in the systemic therapy of AD when other drugs have failed. Mycophenolate mofetil has recently been introduced in the treatment of recalcitrant AD. Efalizumab and omalizumab are monoclonal antibodies with a possible future role in the treatment of AD, but further studies are needed. PMID:19275273

  15. Drug therapy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Chang-Tai Xu; Shu-Yong Meng; Bo-Rong Pan

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn's ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn's ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.

  16. Immunosuppression of canine renal allograft recipients by CD4 and CD8 monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Watson, C.J.E.; Davies, H.S.; Rebello, P.R.U.B.; McNair, R.; Rasmussen, A.; Calne, R.Y.; Metcalfe, S.M. (Department of Surgery, University of Cambridge (United Kingdom)); Cobbold, S.P.; Thiru, S.; Waldmann, H. (Department of Pathology, University of Cambridge (United Kingdom))

    1994-01-01

    A state of tolerance to MHC mismatched allografts can be generated in rodents by treatment with CD4 and CD8 monoclonal antibodies (mAb). In order to transpose this type of therapy to large animals and ultimately to the clinic, a suitable model is required. To this end we have generated a series of mAb to the canine CD4, CD8, and Thy-l antigens and have tested their ability to prevent rejection of renal allografts. Donor-recipient pairs were selected from a colony of mongrel dogs in which untreated rejection of two haplotype-mismatched kidneys occurred by day 7 (defined as a serum creatinine > 300 [mu]mol/l). Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival. Depletion of T cells by a Thy-l mAb prior to surgery only extended graft survival to day 9. However, treating with combinations of mAb up to day 10 (CD4 plus Thy-l; CD4 plus CD8; or CD4 plus CD8 plus Thy-l) prolonged renal allograft function up to 25 days. Combination of the triple mAb therapy with a sub-therapeutic immunosuppressive drug regimen (cyclosporin A plus azathioprine that alone gave a median survival of 15 days) favored survival to a median of 38 days. This protocol also inhibited the antiglobulin response that had curtailed the effects of mAb treatment, opening the way to more extended, and potentially tolerizing, mAb plus drug regimens. (au) (23 refs.).

  17. Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications

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    Trivedi Hargovind L

    2009-01-01

    Full Text Available Abstract Background Chronic Renal Allograft Dysfunction (CRAD is responsible for a large number of graft failures. We have abrogated acute T-cell rejections using Ahmedabad Tolerance Induction Protocol (ATIP with hematopoietic stem cell transplantation (HSCT under non-myeloablative conditioning pre-transplant. However B-cell mediated rejections and CRAD continue to haunt us. We carried out retrospective analysis of renal allograft biopsies performed in the last 4 years to evaluate the effect of ATIP on CRAD. Materials and methods Biopsies diagnosed as per modified Banff criteria belonged to 2 groups: ATIP under low dose immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+ Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies, low dose target specific irradiation, cyclophosphamide, cyclosporin followed by HSCT pre-transplant; controls who opted out of ATIP were transplanted under standard triple drug immunosuppression. Demographics of both groups were comparable. Results Incidence of chronic changes was higher in controls (17.5% vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9 months in the latter. Proteinuria and hypertension were higher in controls (48.4% vs. ATIP (32.7% with chronic transplant glomerulopathy, focal global sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin inhibitor toxicity was higher in ATIP (71.9% vs. 48.4% in controls. Conclusion Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.

  18. Gingival hyperplasia in renal allograft recipients receiving cyclosporin-A and calcium antagonists.

    Science.gov (United States)

    King, G N; Fullinfaw, R; Higgins, T J; Walker, R G; Francis, D M; Wiesenfeld, D

    1993-04-01

    Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The effect of nifedipine on graft function in renal allograft recipients treated with cyclosporin A.

    Science.gov (United States)

    Propper, D J; Whiting, P H; Power, D A; Edward, N; Catto, G R

    1989-08-01

    The effect of the calcium channel antagonist nifedipine on renal allograft function was assessed in two groups of renal transplant recipients at least one year after transplantation. Group 1 comprised 10 patients receiving low-dose prednisolone and cyclosporin A, and Group 2 comprised 9 patients receiving low-dose prednisolone and azathioprine. Before commencing nifedipine, creatinine and sodium clearance rates and the fractional excretion of sodium were similar in both two groups. Lithium clearance rates and the fractional excretion of lithium were, however, significantly lower (p less than 0.01) in Group 1 than in Group 2. The absolute reabsorption of sodium from the distal nephron (p less than 0.01), the absolute reabsorption of water from the distal nephron segment (p less than 0.01) and the fractional reabsorption of sodium from the distal tubule relative to the delivery of sodium from the proximal tubule (p less than 0.05) were also lower in Group 1. After seven days of nifedipine treatment (10 mg/8 h) there was a significant fall in sodium clearance (p less than 0.01) and fractional sodium excretion (p less than 0.05), and an increase in the fractional distal reabsorption of sodium relative to the delivery of sodium from the proximal tubule (p less than 0.01), and the fractional distal reabsorption of water relative to the delivery of water from the proximal tubule (p less than 0.02), in Group 1 but not Group 2. The only alterations observed in Group 2 were an increase in fractional lithium excretion (p less than 0.05), and a significant fall in the absolute proximal tubular reabsorption of iso-osmotic fluids (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. A case of polyarteritis nodosa limited to the right calf muscles, fascia, and skin: a case report

    Directory of Open Access Journals (Sweden)

    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