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Sample records for systemic sclerosis associations

  1. Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis

    International Nuclear Information System (INIS)

    Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

    2010-01-01

    Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

  2. Associations between Systemic Sclerosis and Thyroid Diseases

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2017-10-01

    Full Text Available We have reviewed scientific literature about the association of systemic sclerosis (SSc and thyroid disorders. A high incidence, and prevalence, of new cases of autoimmune thyroiditis (AT and/or hypothyroidism have been shown in sclerodermic patients (overall in the female gender. An association among a Th1 immune-predominance, low vitamin D levels, and AT have been also shown in SSc patients. Cases of Graves’ disease (GD have been described in SSc patients, too, according with the higher prevalence of thyroid autoimmunity. It has been also shown a higher prevalence of papillary thyroid cancer (PTC, in association with AT, in SSc patients. However, in order to confirm results about GD and thyroid cancer, studies in larger number of patients with SSc are needed. During the follow-up of SSc patients it would be appropriate to monitor carefully their thyroid status. The abovementioned data strongly suggest a periodic thyroid function follow-up in female SSc patients [showing a borderline high (although in the normal range thyroid-stimulating hormone level, antithyroid peroxidase antibody positivity, and a small thyroid with a hypoechoic pattern], and, when necessary, appropriate treatments. In conclusion, most of the studies show an association among SSc, AT, and hypothyroidism, such as an increased prevalence of TC overall in SSc patients with AT. Only few cases of GD have been also described in SSc.

  3. Adie’s Tonic Pupil in Systemic Sclerosis: A Rare Association

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    Anusha Venkataraman

    2015-01-01

    Full Text Available We report a rare association of Adie’s tonic pupil in a patient with systemic sclerosis who was otherwise systemically stable. This paper is an effort to unravel whether the tonic pupil and systemic sclerosis are an association by chance (which may be the case or systemic sclerosis is the source of the tonic pupil.

  4. Association of systemic sclerosis and psoriatic arthritis: a case report

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    A. Musio

    2011-09-01

    Full Text Available The association of Systemic Sclerosis (SSc and Psoriatic Arthritis (PsA is unfrequent; only few cases are reported in literature. We describe a case of a patient with SSc following the onset of PsA. The disease begun with tenosynovitis, polyarthritis in association with psoriasis. After two years, Raynaud’s phenomenon and sclerodactyly appeared, and, later, pulmonary interstizial fibrosis and esophageal dysfunction. The existence of a common pathogenesis of the two diseases, SSc and PsA, is discussed.

  5. Pulmonary dystrophic Calcinosis associated to systemic sclerosis: Report of the first case in Colombia

    International Nuclear Information System (INIS)

    Mendez Patarroyo, Paul; Rojas, Adriana; Restrepo Suarez, Jose Felix; Iglesias Gamarra, Antonio

    2002-01-01

    The association of pulmonary calcinosis with systemic sclerosis has not been described in the medical literature. There are two type of lung calcification: dystrophic and metastatic; in the collagen vascular diseases the most frequent is the dystrophic calcinosis, seen mainly in dermatomyositis and scleroderma. We describe the first case of dystrophic calcinosis associated with systemic sclerosis

  6. Erasmus syndrome: Association of silicosis and systemic sclerosis

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    Reena K Sharma

    2018-01-01

    Full Text Available Silicosis is an inflammatory disease of the lung characterized by irreversible lung fibrosis which develops from prolonged pulmonary inhalation and retention of crystalline silica and immune reaction. It mainly appears as an occupational hazard in persons involved in stone-quarrying, mining, and sand blasting. Crystalline silica is not only known to be responsible for silicosis but also for other autoimmune diseases including systemic lupus erythematosus (SLE, rheumatoid arthritis (RA-Caplan syndrome, systemic sclerosis (SSc, and antineutrophil cytoplasmic antibody (ANCA-related vasculitis. Erasmus syndrome is the association of silica exposure and subsequent development of SSc. The limited numbers of cases reported in the literature were miners and only sporadically involved in other professionals. Here, we report a case of a 52 -year-old stone cutter who developed silicosis and SSc after 25 years of exposure.

  7. Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis; Asociacion de LES y esclerosis multiple: esclerosis lupoide.

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    Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

    2010-07-01

    Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

  8. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

    Science.gov (United States)

    Jeong, Anna; Wong, Michael

    2016-09-01

    Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies. Wiley

  9. New insight on the Xq28 association with systemic sclerosis

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    Carmona, F David; Cénit, M Carmen; Diaz-Gallo, Lina-Marcela; Broen, Jasper C A; Simeón, Carmen P; Carreira, Patricia E; Callejas-Rubio, José-Luis; Fonollosa, Vicente; López-Longo, Francisco J; González-Gay, Miguel A; Hunzelmann, Nicolas; Riemekasten, Gabriela; Witte, Torsten; Kreuter, Alexander; Distler, Jörg H W; Madhok, Rajan; Shiels, Paul; van Laar, Jacob M; Schuerwegh, Annemie J; Vonk, Madelon C; Voskuyl, Alexandre E; Fonseca, Carmen; Denton, Christopher P; Herrick, Ariane; Worthington, Jane; Arnett, Frank C; Tan, Filemon K; Assassi, Shervin; Radstake, Timothy R D J; Mayes, Maureen D; Martín, Javier

    2013-01-01

    Objective To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). Methods We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. Results IRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10−3, OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10−4, OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF− (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). Conclusions Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease. PMID:23444193

  10. Clinical pattern of systemic sclerosis in Central Ukraine. Association between clinical manifestations of systemic sclerosis and hypertension.

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    Semenov, Viktor; Kuryata, Olexandr; Lysunets, Tatiana

    2018-01-01

    Systemic sclerosis (SSc) is a rare disease of connective tissue, manifestations of which may vary in different geographical areas. We aimed to describe the clinical portrait of patients with SSc in Dnipropetrovsk region and to investigate how initial clinical and laboratory characteristics are connected with the presence of hypertension in SSc onset. Patients were enrolled to this study from the registry of SSc patients, established in the Rheumatology Department, Mechnikov Dnipropetrovsk Regional Clinic, Dnipro. This registry contains histories of new cases of SSc from 1993 to 2014. Patients are followed-up and receive treatment according to EULAR and local standards. Diagnosis of SSc was based on ACR and EULAR Criteria for systemic Sclerosis. Two patients developed scleroderma renal crisis during follow-up. This report is a cross-sectional study. We analysed only data of the first visit to a rheumatologist. In total 148 patients (median age [IQR] - 47 [40; 52] years) fulfilled the inclusion criteria. Male/female ratio was 1 : 20.1. The most frequent clinical signs were Raynaud's phenomenon and arthritis. The prevalence of skin lesion in dcSSc patients was twice as high as in lcSSc patients. Pulmonary fibrosis occurred significantly more commonly in dcSSc patients. Hypertension occurred in 26-33% in both groups. Patients with hypertension at the SSc onset were seven years older than normotensive patients. More hypertensive patients were classified as lcSSc. Mean GFR was dramatically lower in hypertensive patients. The most common clinical form in our study was diffuse cutaneous subset of SSc. Hypertension in patients with SSc may be associated with local cutaneous subset of SSc and renal impairment. The strongest predictors of clinical form of SSc are signs of fibrosis (skin lesion and pulmonary fibrosis) and inflammation (arthritis and elevated CRP).

  11. Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Sjoberg, R.J.; Blue, P.W.; Kidd, G.S.

    1989-01-01

    Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake

  12. Is there an association between glaucoma and capillaroscopy in patients with systemic sclerosis?

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    Gomes, Beatriz Fiuza; Souza, Rebeca; Valadão, Thiago; Kara-Junior, Newton; Moraes, Haroldo Vieira; Santhiago, Marcony R

    2018-02-01

    To evaluate the relationship between glaucoma diagnosis and the nailfold capillaroscopy pattern in patients with systemic sclerosis. An observational study in a cohort of patients with SSc was conducted. Patients with at least one nailfold videocapillaroscopy and one ophthalmology examination at the same year were included. Data collected were: age, sex; type of systemic sclerosis according to the degree of skin impairment, self-reported ethnicity, disease duration, current use and dosage of systemic corticosteroid, current use and dosage of bosentan ® , intraocular pressure, central corneal thickness, diagnosis of glaucoma and capillaroscopy pattern. Thirty-one patients with systemic sclerosis were enrolled, 23% had glaucoma. There was no statistically significant association between glaucoma diagnosis and the capillaroscopic pattern (p = 0.86). There was also no significant difference (p = 0.66) regarding intraocular pressure between patients with mild (13.9 ± 3.8 mmHg) and severe capillaroscopic pattern (14.4 ± 2.8 mmHg). The odds ratio of glaucoma for severe capillaroscopic pattern compared to mild was 1.6 (95% confidence interval: 0.3-9.5). Up to 23% of patients with SSc have glaucoma. The high prevalence of glaucoma in SSc suggests a possible systemic vascular disturbance as the cause. However, there seems to be no significant association between the capillaroscopy pattern and glaucoma in systemic sclerosis. Further research is required to improve the understanding of glaucoma in the context of systemic sclerosis.

  13. Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Sjoberg, R.J.; Blue, P.W.; Kidd, G.S.

    1989-01-01

    Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake.

  14. Oral and periodontal manifestations associated with systemic sclerosis: A case series and review

    OpenAIRE

    Rekha Jagadish; Dhoom Singh Mehta; P Jagadish

    2012-01-01

    Systemic sclerosis is a rare connective tissue disorder with a wide range of oral manifestations. This case series reports significant oral and periodontal changes and also makes an attempt to correlate oral and systemic findings in these patients which enable the clinician for a better diagnosis and evolve a comprehensive treatment plan. Six patients with a known diagnosis of systemic sclerosis were included. After obtaining the patient's informed consent, relevant medical history, oral mani...

  15. The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis

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    Beretta, Lorenzo; Simeón, Carmen P.; Carreira, Patricia E.; Callejas, José Luis; Fernández-Castro, Mónica; Sáez-Comet, Luis; Beltrán, Emma; Camps, María Teresa; Egurbide, María Victoria; Airó, Paolo; Scorza, Raffaella; Lunardi, Claudio; Hunzelmann, Nicolas; Riemekasten, Gabriela; Witte, Torsten; Kreuter, Alexander; Distler, Jörg H. W.; Madhok, Rajan; Shiels, Paul; van Laar, Jacob M.; Fonseca, Carmen; Denton, Christopher; Herrick, Ariane; Worthington, Jane; Schuerwegh, Annemie J.; Vonk, Madelon C.; Voskuyl, Alexandre E.; Radstake, Timothy R. D. J.; Martín, Javier

    2013-01-01

    Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10−8, OR  = 1.22, CI 95%  = 1.14–1.30; rs2004640: P  = 4.60×10−7, OR  = 0.84, CI 95%  = 0.78–0.90; rs10488631: P  = 7.53×10−20, OR  = 1.63, CI 95%  = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10−22, OR  = 1.75, CI 95%  = 1.56–1.97) better explained the observed association (likelihood P-value  = 1.48×10−4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that

  16. Oral and periodontal manifestations associated with systemic sclerosis: A case series and review.

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    Jagadish, Rekha; Mehta, Dhoom Singh; Jagadish, P

    2012-04-01

    Systemic sclerosis is a rare connective tissue disorder with a wide range of oral manifestations. This case series reports significant oral and periodontal changes and also makes an attempt to correlate oral and systemic findings in these patients which enable the clinician for a better diagnosis and evolve a comprehensive treatment plan. Six patients with a known diagnosis of systemic sclerosis were included. After obtaining the patient's informed consent, relevant medical history, oral manifestations including periodontal findings and oral hygiene index simplified index were recorded. In these patients, oral changes included restricted mouth opening and, resorption of the mandible. The periodontal changes observed were gingival recession, absence or minimal gingival bleeding on probing, and widened periodontal ligament space, radiographically. Patients with systemic sclerosis often show wide range of oral manifestations, which is of major concern for the dentist.

  17. Oral and periodontal manifestations associated with systemic sclerosis: A case series and review

    Directory of Open Access Journals (Sweden)

    Rekha Jagadish

    2012-01-01

    Full Text Available Systemic sclerosis is a rare connective tissue disorder with a wide range of oral manifestations. This case series reports significant oral and periodontal changes and also makes an attempt to correlate oral and systemic findings in these patients which enable the clinician for a better diagnosis and evolve a comprehensive treatment plan. Six patients with a known diagnosis of systemic sclerosis were included. After obtaining the patient′s informed consent, relevant medical history, oral manifestations including periodontal findings and oral hygiene index simplified index were recorded. In these patients, oral changes included restricted mouth opening and, resorption of the mandible. The periodontal changes observed were gingival recession, absence or minimal gingival bleeding on probing, and widened periodontal ligament space, radiographically. Patients with systemic sclerosis often show wide range of oral manifestations, which is of major concern for the dentist.

  18. Perceived functioning has ethnic-specific associations in systemic sclerosis: another dimension of personalized medicine.

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    McNearney, Terry A; Hunnicutt, Sonya E; Fischbach, Michael; Friedman, Alan W; Aguilar, Martha; Ahn, Chul W; Reveille, John D; Lisse, Jeffrey R; Baethge, Bruce A; Goel, Niti; Mayes, Maureen D

    2009-12-01

    To measure self-reported physical and mental functioning and associated clinical features at study entry in 3 ethnic groups with systemic sclerosis (SSc). Sixty Hispanic, 39 African American, and 104 Caucasian patients with recent-onset SSc ( fatigue scores > IBQ > clinical variables (hypertension, skin score, and percentage predicted DLCO). Scleroderma-HAQ scores had ethnic-specific associations with IBQ > AHI scores > most clinical and laboratory variables. Decreased mental component summary (MCS) scores associated with AHI > ISEL. Ethnic-specific immunogenetic variables HLA-DQB1*0202 (Caucasian) and HLA-DRB 1*11 (African American), and HLA-DQA1*0501 (Hispanic) also associated with MCS. Antinuclear autoantibodies, anti-topoisomerase I, and RNA polymerases I and III also demonstrated associations with functioning in African American and Hispanic groups. Clinical, psychosocial, and immunogenetic variables had ethnic-specific associations with perceived physical and mental functioning. Consideration of ethnic-specific psychological and behavioral support in designing more personalized, relevant therapeutic interventions for the patient may improve therapeutic efficacy in SSc.

  19. A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis.

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    Peng, Wen-jia; Pan, Hai-feng; Tao, Jin-hui; Wang, Bing-xiang; Lu, Man-man; Wang, Song; He, Qian; Wang, Jing

    2012-09-01

    We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39-0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.

  20. Association of the FAM167A-BLK region with systemic sclerosis.

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    Ito, Ikue; Kawaguchi, Yasushi; Kawasaki, Aya; Hasegawa, Minoru; Ohashi, Jun; Kawamoto, Manabu; Fujimoto, Manabu; Takehara, Kazuhiko; Sato, Shinichi; Hara, Masako; Tsuchiya, Naoyuki

    2010-03-01

    An association of single-nucleotide polymorphisms (SNPs) in the FAM167A (previously referred to as C8orf13)-BLK region with systemic lupus erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared susceptibility genes in multiple autoimmune diseases. We undertook the current study to examine whether the FAM167A-BLK region is also associated with susceptibility to systemic sclerosis (SSc). Japanese patients with SSc (n = 309) and healthy controls (n = 769) were enrolled in a 2-tiered case-control association study. In tier 1, 124 patients and 412 controls were tested to determine association of 16 tag SNPs encompassing the FAM167A-BLK region with SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP rs13277113. Two haplotype blocks that correspond approximately to FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in the BLK block exhibited the most significant association with SSc after correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed by rs13277113 and the most significant SNP in the FAM167A block did not exhibit stronger association. When samples from tier 1 and tier 2 were combined, the rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95% confidence interval 1.17-1.79], P = 6.1 x 10(-4)). Association or a tendency toward association of rs13277113A with SSc was observed regardless of a patient's autoantibody profile or whether a patient had diffuse cutaneous or limited cutaneous SSc. Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc.

  1. Molecular subtypes of systemic sclerosis in association with anti-centromere antibodies and digital ulcers

    NARCIS (Netherlands)

    Bos, C. L.; van Baarsen, L. G. M.; Timmer, T. C. G.; Overbeek, M. J.; Basoski, N. M.; Rustenburg, F.; Baggen, J. M. C.; Thiesen, H. J.; Dijkmans, B. A. C.; van der Pouw Kraan, T. C. T. M.; Voskuyl, A. E.; Verweij, C. L.

    2009-01-01

    The objective of this study was to identify molecular profiles that may distinguish clinical subtypes in systemic sclerosis (SSc). Large-scale gene expression profiling was performed on peripheral blood (PB) from 12 SSc patients and 6 healthy individuals. Significance analysis of microarrays,

  2. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement

    DEFF Research Database (Denmark)

    Nordenbaek, C; Johansen, J S; Halberg, P

    2005-01-01

    OBJECTIVES: YKL-40, a growth factor of connective tissue cells, is elevated in sera from patients with diseases characterized by inflammation, tissue remodelling, or fibrosis. The aim of the study was to determine serum YKL-40 levels in patients with systemic sclerosis (SSc) and to explore any po...

  3. [Hashimoto thyroiditis may be associated with a subset of patients with systemic sclerosis with pulmonary hypertension].

    Science.gov (United States)

    Costa, Ciliana Cardoso B; Medeiros, Morgana; Watanabe, Karen; Martin, Patricia; Skare, Thelma L

    2014-01-01

    Recent studies show an association between autoimmune thyroiditis and systemic sclerosis (SSc) and suggest that this condition may interfere with the ES phenotype. However these studies evaluate the autoimmune thyroiditis as a whole and none of them specifically addresses Hashimoto's thyroiditis (HT) in SSc. To investigate the presence of HT in SSc patients and its possible association with disease manifestations. Clinical manifestations of hypothyroidism, TSH and anti-thyroid auto antibodies (anti-TPO. anti TBG and TRAb) were studied in 56 patients with SSc. SSc patients with HT were compared with SSc patients without thyroiditis. HT was observed in 19.64% of patients with SSc. No association was observed between HT and the different forms of disease or profile of autoantibodies. Likewise, there was no difference between the mean modified Rodnan score and presence of Raynaud's phenomenon, scars, digital necrosis, myositis, arthritis, sicca symptoms, esophageal dysmotility and scleroderma renal crisis when the groups were compared. On the other hand, patients with HT had higher frequency of pulmonary hypertension in relation to patients without HT (66.6% vs 22.5%, p=0.016). In the studied sample patients with ES and HT had higher prevalence of pulmonary hypertension. Long-term follow-up studies with a larger number of TH and SSc patients are needed to confirm these data. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  4. Capillary loss on nailfold capillary microscopy is associated with mortality in systemic sclerosis.

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    Pavan, Thais Rohde; Bredemeier, Markus; Hax, Vanessa; Capobianco, Karina Gatz; da Silva Mendonça Chakr, Rafael; Xavier, Ricardo Machado

    2018-02-01

    The objective of this study is to test the association of the severity of nailfold capillaroscopy (NFC) abnormalities with mortality in systemic sclerosis (SSc). One hundred and seventy SSc patients underwent an extensive evaluation (including high-resolution computed tomography, pulmonary function tests, and Doppler echocardiography) at baseline following a standard protocol. Capillary loss on NFC was evaluated using the avascular score (AS, ranging from 0 to 3), and the mean number of ectasias, megacapillaries, and hemorrhages per finger was also recorded. After a mean period of 10.1 ± 4.9 years, the life status of the patients was ascertained. Univariate and multivariate Cox proportional hazards models were used for statistical analysis. Overall, 73 patients died. By univariate Cox analysis, the AS was significantly associated with mortality (hazard ratio [HR] = 1.64, 95% CI 1.22 to 2.19, p = 0.001). In our study, this association was stronger than that of race, gender, anticentromere antibodies, anti-topoisomerase I antibodies, and form of disease and had similar strength to that of skin score in univariate analyses. However, after controlling for a combination of variables (age, skin score, gender, race, signs of peripheral ischemia, and extent of interstitial lung disease, all independently associated with mortality), the association of AS with mortality was blunted (HR = 1.15, 95% CI 0.80 to 1.65, p = 0.445). Other NFC variables were not related to mortality. AS was associated with higher risk of death and, despite not having an independent association with mortality after controlling for a set of demographic and clinical variables, may be a useful tool in prognostic evaluation of SSc.

  5. Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

    Science.gov (United States)

    Arana-Guajardo, Ana Cecilia; Barrera-Torres, Gustavo; Villarreal-Alarcón, Miguel Ángel; Vega-Morales, David; Esquivel-Valerio, Jorge Antonio

    2017-12-16

    The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. Factors associated with oral hygiene practices among adults with systemic sclerosis.

    Science.gov (United States)

    Yuen, H K; Hant, F N; Hatfield, C; Summerlin, L M; Smith, E A; Silver, R M

    2014-08-01

    To identify factors associated with oral hygiene practices in adults with systemic sclerosis (SSc). In this cross-sectional study, 178 dentate adults with SSc received an oral examination which included measurement of oral aperture, assessment of manual dexterity to perform oral hygiene, as well as completion of the Center of Epidemiological Studies Depression (CES-D) Scale and an oral health-related questionnaire. Multivariable logistic regression modelling showed male, minority and high CES-D scores (i.e. clinically significant symptoms of depression) were associated with less likelihood of participants brushing teeth at least twice daily, but the presence of self-reported dry mouth symptoms increased the likelihood of toothbrushing. Having a dental visit in the past 12 months and use of an adapted flossing or interdental cleaning device were significantly associated with daily dental flossing; however, having difficulty flossing teeth reduced the likelihood of daily flossing. Overall, demographic variables were strongly associated with toothbrushing frequency, whereas flossing self-efficacy and barriers were strongly associated with dental flossing frequency in adults with SSc. The results suggest that dental health professionals should take mental health into consideration when educating patients with SSc to improve their oral hygiene and consider making referrals for patients exhibiting suspected clinically significant depressive symptoms to mental health professionals for further evaluation and treatment. In addition, an appropriate adapted flossing or interdental cleaning device should be recommended to increase dental flossing practices in this patient population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Association between nailfold capillaroscopy findings and pulmonary function tests in patients with systemic sclerosis.

    Science.gov (United States)

    Castellví, Ivan; Simeón-Aznar, Carmen Pilar; Sarmiento, Mónica; Fortuna, Ana; Mayos, Mercedes; Geli, Carme; Diaz-Torné, César; Moya, Patricia; De Llobet, Josep Maria; Casademont, Jordi

    2015-02-01

    To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

  8. Erasmus Syndrome: Silicosis and Systemic Sclerosis.

    Science.gov (United States)

    Jain, Shubhra; Joshi, Vinod; Rathore, Yogendra S; Khippal, Narendra

    2017-01-01

    Several occupational hazards, especially exposure to silica, have been implicated as causal factors for the development of scleroderma-like disorders. Compared to other connective tissue disorders, silica-associated systemic sclerosis (SA-SS) is relatively rare. Silica-induced scleroderma is indistinguishable from idiopathic systemic sclerosis. However, the former expresses a high predisposition of pulmonary involvement and anti-Scl-70 antibody. We report the case of a 42-year-old male, stone cutter by occupation, who was diagnosed as simple chronic silicosis and developed systemic sclerosis.

  9. Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zarir F Udwadia

    2015-01-01

    Full Text Available Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF. However, its role in interstitial lung disease (ILD due to other causes such as systemic sclerosis (SSc is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.

  10. In systemic sclerosis, anxiety and depression assessed by hospital anxiety depression scale are independently associated with disability and psychological factors.

    OpenAIRE

    Del Rosso, A; Mikhaylova, S; Baccini, M; Lupi, I; Matucci Cerinic, M; Maddali Bongi, S

    2013-01-01

    Background. Anxious and depressive symptoms are frequent in Systemic Sclerosis (SSc). Our objective is to assess their prevalence and association with district and global disability and psychological variables. Methods. 119?SSc patients were assessed by Hospital Anxiety Depression Scale (HADS). Clinical depression and anxiety were defined for HADS score cutoff ?8. Patients were assessed for psychological symptoms (RSES, COPE-NIV), hand (HAMIS, CHFDS, fist closure, and hand opening) and face d...

  11. The association of illness perceptions with physical and mental health in systemic sclerosis patients: an exploratory study.

    Science.gov (United States)

    Arat, Seher; Verschueren, Patrick; De Langhe, Ellen; Smith, Vanessa; Vanthuyne, Marie; Diya, Luwis; Van den Heede, Koen; Blockmans, Daniel; De Keyser, Filip; Houssiau, Frédéric A; Westhovens, René

    2012-03-01

    The aim of the present study was to evaluate the association between illness perceptions and the ability to cope with physical and mental health problems in a large cohort of systemic sclerosis (SSc) patients. This was a cross-sectional study in 217 systemic sclerosis patients from the Belgian Systemic Sclerosis Cohort. Illness perception and coping were measured by the Revised Illness Perception Questionnaire and a coping questionnaire--the Coping Orientation of Problem Experience inventory (COPE). Physical and mental health-related quality of life was measured by the 36-item short-form health survey (SF-36), as were disease activity and several severity parameters. The relationship between illness perceptions and the ability to cope with physical/mental health problems was examined using multiple linear regression analysis. According to LeRoy's classification, 49 patients had limited SSc (lSSc), 129 had limited cutaneous SSc (lcSSc) and 39 had diffuse cutaneous SSc (dcSSc). Median disease duration was five years and the modified Rodnan skin score was 4. Good physical health was significantly associated with the lcSSc subtype and low disease activity (p consequences' and strong 'illness identity' correlated with poor physical health (p mental health was associated with low illness identity scores and low 'emotional response' scores (p mental health compared with the illness perception items. Illness representations contribute more than classical disease characteristics to physical and mental health. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Radiological pleuroparenchymal fibroelastosis associated to limited cutaneous systemic sclerosis: a case report.

    Science.gov (United States)

    Hassoun, D; Dirou, S; Arrigoni, P P; Durant, C; Hamidou, M; Néel, A; Agard, C

    2018-05-18

    Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes. PPFE-like lesions have recently been described in patients with connective tissue disease (CTD)-related ILD. We report here the first detailed case of PPFE associated to systemic sclerosis (SSc) in a woman free of telomeropathy mutations. A caucasian 46 year old woman was followed for SSc in a limited form with anti-centromere Ab since 1998, and seen in 2008 for a routine visit. Her SSc was stable, and she had no respiratory signs. Pulmonary function tests showed an isolated decreased cTLCO at 55.9% (of predicted value). Cardiac ultrasonography was normal. Thoracic CT-scan showed upper lobes predominant mild and focal pleural and subpleural thickenings, suggestive of PPFE, with a slight worsening at 8 years of follow-up. She remained clinically stable. Biology only found a moderate and stable peripheral thrombocytopenia, and sequencing analysis did not find any mutations in TERT and TERC genes. ILD is frequent in SSc but isolated PPFE has never been described so far. In our case, PPFE is not related to telomeropathy, has indolent outcome and seems to have good prognosis. PPFE might be an extremely rare form of SSc-related ILD, although a fortuitous association remains possible.

  13. Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk

    DEFF Research Database (Denmark)

    Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J

    2018-01-01

    Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18...... and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1......,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion...

  14. Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

    OpenAIRE

    Teruel, María; Simeón Aznar, Carmen Pilar; Broen, Jasper C.; Vonk, Madelon C.; Carreira, Patricia; Camps García, María Teresa; García-Portales, Rosa; Delgado-Frías, Esmeralda; Gallego, Maria; Espinosa Garriga, Gerard; Spanish Scleroderma Group; Beretta, Lorenzo; Airó, Paolo; Lunardi, Claudio; Riemekasten, Gabriela

    2012-01-01

    Introduction: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genot...

  15. Skin scoring in systemic sclerosis

    DEFF Research Database (Denmark)

    Zachariae, Hugh; Bjerring, Peter; Halkier-Sørensen, Lars

    1994-01-01

    Forty-one patients with systemic sclerosis were investigated with a new and simple skin score method measuring the degree of thickening and pliability in seven regions together with area involvement in each region. The highest values were, as expected, found in diffuse cutaneous systemic sclerosis...... (type III SS) and the lowest in limited cutaneous systemic sclerosis (type I SS) with no lesions extending above wrists and ancles. A positive correlation was found to the aminoterminal propeptide of type III procollagen, a serological marker for synthesis of type III collagen. The skin score...

  16. Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

    Directory of Open Access Journals (Sweden)

    Olga Gorlova

    2011-07-01

    Full Text Available The aim of this study was to determine, through a genome-wide association study (GWAS, the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc. We considered limited (lcSSc and diffuse (dcSSc cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA, and anti-topoisomerase I (ATA. Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12, OR = 0.75. Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6, OR = 1.15 and rs11047102 in SOX5 gene (P = 1.39×10(-7, OR = 1.36 showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61, OR = 2.48, in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76, OR = 8.84, and in NOTCH4 with ACA P = 8.84×10(-21, OR = 0.55 and ATA (P = 1.14×10(-8, OR = 0.54. We have identified three new non-HLA genes (IRF8, GRB10, and SOX5 associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.

  17. Lung disease associated with progressive systemic sclerosis. Assessment of interlobar variation by bronchoalveolar lavage and comparison with noninvasive evaluation of disease activity

    International Nuclear Information System (INIS)

    Miller, K.S.; Smith, E.A.; Kinsella, M.; Schabel, S.I.; Silver, R.M.

    1990-01-01

    Progressive systemic sclerosis (PSS), or scleroderma, is a disease of unknown etiology that involves many organ systems, including the lungs. The interstitial lung disease of systemic sclerosis is becoming an increasing cause of morbidity and mortality. This process has been previously evaluated with single-site bronchoalveolar lavage (BAL), gallium scanning, pulmonary function testing, and, occasionally, by open lung biopsy. As BAL has been shown to correlate well with open lung biopsy in systemic sclerosis, we sought to determine if single-site BAL accurately reflects alveolitis in a second site in the lung, and if BAL results correlate with other noninvasive tests of lung inflammation: gallium uptake, chest radiography, or arterial blood gas analysis. We performed 17 studies in 13 patients with scleroderma and found no significant lobar differences in lavage results or gallium scanning. By our criteria for normal versus active alveolitis, only two of 17 patient lavages would have been classified as normal by one side and abnormal by the other side. Although percent gallium uptake was equal bilaterally and supported the concept of alveolitis uniformity, gallium uptake intensity did not correlate with activity as measured by BAL. Furthermore, chest radiograph and arterial blood gas analysis did not correlate with BAL results or gallium scanning. We believe these data support the suitability of single-site lavage in the investigation of systemic-sclerosis-associated alveolitis and diminish the importance of gallium scanning in the investigation of systemic sclerosis pulmonary disease

  18. Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

    Science.gov (United States)

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  19. HLA typing in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    M. Faré

    2011-09-01

    Full Text Available Objective: the aim of the study was to investigate the relationship between Systemic Sclerosis (SSc and HLA antigens, and to correlate these antigens with the clinical manifestations of the disease. Materials and methods: 55 patients were stratified according a to the cutaneous involvement b to the positivity of Scl- 70 and anticentromere antibody and c to the internal organ involvement, in particular we used HRCT to demonstrate lung fibrosis, echocardiography for the diagnosis of pulmonary hypertension, blood creatinine, urinalysis and arterial hypertension to demonstrate renal failure, and esophagus double-countrast barium swallow for the diagnosis of esophagopathy. The control group consisting of 2000 healthy Caucasian subjects was recruited from the same population. Results: the frequency of the antigens A23 (p=0.003, RR=3.69, B18 (p<0.0001, RR=3.57, and DR11 (p<0.0001, RR=6.18 was statistically increased in the patients population compared with the healthy controls. Although there is no any significant correlation between HLA antigens and different clinical subsets of scleroderma, antigens B18 and DR11 could be associated with more severe clinical features. Conclusions: the presence of a significant association between SSc and specific HLA antigens (A23, B18, and DR11 could link the HLA system with SSc.

  20. An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis

    NARCIS (Netherlands)

    Bossini-Castillo, Lara; Campillo-Davo, Diana; Lopez-Isac, Elena; Carmona, Francisco David; Simeon, Carmen P.; Carreira, Patricia; Callejas-Rubio, Jose Luis; Castellvi, Ivan; Fernandez-Nebro, Antonio; Rodriguez-Rodriguez, Luis; Rubio-Rivas, Manel; Garcia-Hernandez, Francisco J.; Madronero, Ana Belen; Beretta, Lorenzo; Santaniello, Alessandro; Lunardi, Claudio; Airo, Paolo; Hoffmann-Vold, Anna-Maria; Kreuter, Alexander; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Vonk, Madelon C.; Voskuyl, Alexandre E.; de Vries-Bouwstra, Jeska; Shiels, Paul; Herrick, Ariane; Worthington, Jane; Radstake, Timothy R.D.J.; Martin, Javier

    2017-01-01

    Objective. Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in patients with SSc. However, the genetic factors involved in lung complication are not well defined. We aimed to

  1. The magnitude of cytokine production by stimulated CD56+ cells is associated with early stages of systemic sclerosis

    NARCIS (Netherlands)

    Cossu, Marta; van Bon, L.; Nierkens, S; Bellocchi, Chiara; Santaniello, Alessandro; Dolstra, H.; Beretta, Lorenzo; Radstake, TRDJ

    2016-01-01

    Immune activation is a hallmark of systemic sclerosis (SSc). However, the immunological alterations that occur in preclinical and non-fibrotic SSc and that differentiate these subjects from those with primary Raynaud's phenomenon (PRP) or healthy controls (HC) are poorly defined. We isolated CD56+

  2. Cavernous angioma associated with ipsilateral hippocampal sclerosis

    International Nuclear Information System (INIS)

    Okujava, M.; Ebner, A.; Schmitt, J.; Woermann, F.G.

    2002-01-01

    We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

  3. Cavernous angioma associated with ipsilateral hippocampal sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Okujava, M [Institute of Radiology and Interventional Diagnostics, Tbilisi (Georgia); Ebner, A; Schmitt, J; Woermann, F G [Bethel Epilepsy Centre, Mara Hospital, Bielefeld (Germany)

    2002-07-01

    We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

  4. Evidence for chronic inflammation as a component of the interstitial lung disease associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Rossi, G.A.; Bitterman, P.B.; Rennard, S.I.; Ferrans, V.J.; Crystal, R.G.

    1985-01-01

    Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a ''pure'' fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least one mechanism modulating the lung fibrosis of these patients

  5. In Systemic Sclerosis, Anxiety and Depression Assessed by Hospital Anxiety Depression Scale Are Independently Associated with Disability and Psychological Factors

    Directory of Open Access Journals (Sweden)

    Angela Del Rosso

    2013-01-01

    Full Text Available Background. Anxious and depressive symptoms are frequent in Systemic Sclerosis (SSc. Our objective is to assess their prevalence and association with district and global disability and psychological variables. Methods. 119 SSc patients were assessed by Hospital Anxiety Depression Scale (HADS. Clinical depression and anxiety were defined for HADS score cutoff ≥8. Patients were assessed for psychological symptoms (RSES, COPE-NIV, hand (HAMIS, CHFDS, fist closure, and hand opening and face disability (MHISS, mouth opening, global disability, and fatigue (HAQ, FACIT. Results. Both depression and anxiety in SSc are 36%. Depressive patients with comorbid anxiety have higher HADS-D score than patients with depression only (. HADS-A and -D are positively correlated with global disability, hands and mouth disability, fatigue, self-esteem and avoidance coping strategy, and, only HADS-A, also with social support (. By multiple regression, HADS-D is independently associated with FACIT-F (, RSES (, and MHISS total score (, together explaining 50% of variance. HADS-A is independently associated with RSES (, COPE-NIV SA (, COPE-NIV SS (, FACIT-F (, and MHISS mouth opening (, explaining 41% of variance. Conclusions. In SSc depression and anxiety correlate to local and global disabilities and psychological characteristics. Depressive patients with comorbid anxiety have higher level of depressive symptoms.

  6. Mapping and predicting mortality from systemic sclerosis

    DEFF Research Database (Denmark)

    Elhai, Muriel; Meune, Christophe; Boubaya, Marouane

    2017-01-01

    OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-ca....... With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival....

  7. The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms.

    Science.gov (United States)

    Zhao, Wenjie; Yue, Xiaoyang; Liu, Kuai; Zheng, Junfeng; Huang, Runda; Zou, Jun; Riemekasten, Gabriela; Petersen, Frank; Yu, Xinhua

    2017-08-01

    Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF + -SSc and PF - -SSc patients to identify genetic polymorphisms associated with the status of PF in SSc. Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 × 10 -2 ), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 × 10 -3 ), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not. Since IRF5, STAT4, and IRAK1 are important regulatory factors in the control of innate immune responses and CTGF is involved in the synthesis of extracellular matrix, these results suggest a role of the innate immunity and matrix compounds in the pathogenesis of PF in SSc.

  8. The association between multiple sclerosis and uveitis

    DEFF Research Database (Denmark)

    Olsen, Tine Gadegaard; Frederiksen, Jette

    2016-01-01

    The association between multiple sclerosis (MS) and uveitis has been questioned. Nerve tissue and eye tissue develop from the same embryonic cells; thus, MS and uveitis could be etiologically associated. In published studies, the prevalence of MS in patients with uveitis differe from 0.7% to 30...

  9. Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.

    Science.gov (United States)

    Gorlova, Olga Y; Li, Yafang; Gorlov, Ivan; Ying, Jun; Chen, Wei V; Assassi, Shervin; Reveille, John D; Arnett, Frank C; Zhou, Xiaodong; Bossini-Castillo, Lara; Lopez-Isac, Elena; Acosta-Herrera, Marialbert; Gregersen, Peter K; Lee, Annette T; Steen, Virginia D; Fessler, Barri J; Khanna, Dinesh; Schiopu, Elena; Silver, Richard M; Molitor, Jerry A; Furst, Daniel E; Kafaja, Suzanne; Simms, Robert W; Lafyatis, Robert A; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Beltran, Emma; Ortego, Norberto; Amos, Christopher I; Martin, Javier; Mayes, Maureen D

    2018-01-01

    Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly

  10. Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis

    DEFF Research Database (Denmark)

    Avouac, Jerome; Walker, Ulrich; Tyndall, Alan

    2010-01-01

    To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc).......To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc)....

  11. Calcinosis is associated with digital ischaemia in systemic sclerosis-a longitudinal study.

    Science.gov (United States)

    Baron, Murray; Pope, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Kaminska, Elzbieta; Masetto, Ariel; Sutton, Evelyn; Mathieu, Jean-Pierre; Ligier, Sophie; Grodzicky, Tamara; LeClercq, Sharon; Thorne, Carter; Gyger, Geneviève; Smith, Douglas; Fortin, Paul R; Larché, Maggie; Abu-Hakima, Maysan; Rodriguez-Reyna, Tatiana S; Cabral-Castaneda, Antonio R; Fritzler, Marvin J; Wang, Mianbo; Hudson, Marie

    2016-12-01

    To determine if ischaemia is a causal factor in the development of calcinosis in SSc. Patients with SSc were assessed yearly. Physicians reported the presence of calcinosis, digital ischaemia (digital ulcers, digital necrosis/gangrene, loss of digital pulp on any digits and/or auto- or surgical digital amputation) and nailfold capillary dropout assessed using a dermatoscope. The number of digits with digital ischaemia was used as an assessment of the severity of digital ischaemia. SSc specific antibodies were detected with a line immunoassay. Multiple logistic regression and Cox proportional hazards models were generated to determine associations between calcinosis, digital ischaemia and capillary dropout. One thousand three hundred and five patients were included in this study, of whom 300 (23.0%) had calcinosis at study entry. In a cross-sectional multivariate analysis, at baseline, calcinosis was associated with digital ischaemia (odds ratio (OR) = 2.37, 95% CI: 1.66, 3.39), severity of ischaemia (OR = 1.12, 95% CI: 1.06, 1.18), capillary dropout (OR = 1.41, 95% CI: 1.05, 1.89), ACAs (OR = 1.68, 95% CI: 1.17, 2.43) and anti-RNA polymerase III antibodies (OR = 1.77, 95% CI: 1.08, 2.89). Current use of calcium channel blockers was inversely associated with the presence of calcinosis (OR = 0.70, 95% CI: 0.52, 0.96). Of the 805 patients with no calcinosis at study entry and at least one follow-up visit, 215 (26.7%) developed calcinosis during follow-up. Significant baseline predictors of the development of calcinosis in follow-up were digital ischaemia (hazard ratio (HR) = 1.82, 95% CI: 1.30, 2.54), capillary dropout (HR = 1.46, 95% CI: 1.08, 1.99), dcSSc (HR = 1.57, 95% CI: 1.11, 2.21), ACA (HR = 2.18, 95% CI: 1.50, 3.17) and anti-RNA polymerase III antibodies (HR = 2.58, 95% CI: 1.65, 4.04). Ischaemia may play a role in the development of calcinosis in SSc. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

  12. Improvement of fatigue in multiple sclerosis by physical exercise is associated to modulation of systemic interferon response.

    Science.gov (United States)

    Mulero, Patricia; Almansa, Raquel; Neri, María José; Bermejo-Martin, Jesús Francisco; Archanco, Miguel; Arenillas, Juan Francisco; Téllez, Nieves

    2015-03-15

    Mechanisms underlying multiple sclerosis (MS) fatigue and the causes of the beneficial effect of exercise on this symptom are not clarified. Our aim was to evaluate gene expression profiles in MS patients who improved their fatigue status after an exercise program and to compare them with healthy controls (HC). Gene expression in whole blood was profiled at baseline in 7 HC and also in 7 fatigued-MS patients. Patients underwent an exercise program for 6 months, and their fatigue status and gene expression profiles were again analyzed. MS patients showed a significant activation of genes participating in the systemic interferon response in comparison with HC that disappeared at the end of the program. Our results provide a biological basis for the observed benefit of exercise in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Gradual progression of intrapulmonary lymph nodes associated with usual interstitial pneumonia in progressive systemic sclerosis on chest radiographs and CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohm, Joon Young; Chung, Myung Hee; Kim, Seon Mun [The Catholic Univ. of Korea, Seoul (Korea, Republic of); Kim, Yong Hyun [The Catholic Univ. of Korea, Bucheon (Korea, Republic of)

    2012-10-15

    A 40 year old female visited the clinic for evaluation of Raynaud's phenomenon for a period of four years. The initial chest radiograph showed a fine reticular density and ground glass opacity with lower lobe predominance. These findings are consistent interstitial fibrosis. Additionally, high resolution CT showed multiple, small, coexisting nodular opacities, ranging from 3 to 7 mm in size in both lungs. These nodules grew up to 1.5 cm and showed moderate enhancement. Because of the rareness of intrapulmonary lymph node in patient of progressive systemic sclerosis, we couldn't exclude the possibility of malignancy. These nodules are turned out to be intrapulmonary lymph nodes on video assisted thoracoscopic lung biopsy.

  14. Tomography patterns of lung disease in systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida, E-mail: andrealb@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina

    2016-09-15

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

  15. Tomography patterns of lung disease in systemic sclerosis

    International Nuclear Information System (INIS)

    Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida

    2016-01-01

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

  16. Tomography patterns of lung disease in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Andréa de Lima Bastos

    Full Text Available Abstract Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed, Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses.

  17. Endothelin-1 in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    C. Pizzorni

    2011-09-01

    Full Text Available We evaluated endothelin-1 (ET-1 plasma levels in patients affected by primary Raynaud’s phenomenon (PRP, as well as in patients with systemic sclerosis (SSc and secondary Raynaud’s phenomenon (SRP. Furthermore, ET-1 levels were investigated in SSc patients with different patterns of peripheral microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC. Methods: 23 PRP patients, 67 SSc patients according to ACR criteria, and 23 healthy subjects were enrolled. SSc microvascular involvement was classified in three different patterns (Early, Active, and Late by NVC, as previously described. Results: ET-1 was found significantly higher in both PRP and SRP, when compared with controls (median ±IQR: 3.3±2.8, 2.7±2.2, 2.0±2.2, respectively (p=0.05. No statistically significant difference of ET-1 levels was observed between PRP and SRP patients. ET-1 was found higher in patients with Late NVC pattern, when compared with both Active and Early NVC patterns (median±IQR: 3.4±2.5, 2.4±2.2, 2.5±2.1, respectively, but without statistical significance. Patients with Late NVC pattern showed significantly higher ET-1 plasma levels than controls (p=0.03. No correlation was found between ET-1 levels and disease duration in both groups, as well as between ET-1 levels and age of patients. Conclusions: These data support previous studies, reporting increased ET-1 plasma levels in both PRP and SRP patients. Interestingly, patients with the Late NVC pattern of microangiopathy showed higher ET-1 plasma levels than controls. The high levels of ET-1 detected in the Late NVC pattern of microangiopathy might be related to the larger fibrotic involvement typical of the advanced stages of disease.

  18. Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Broholm, B.; Ullman, S.; Halberg, P.

    2008-01-01

    of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according......Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study......M RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association...

  19. Autoantibodies in systemic sclerosis: Unanswered questions

    Directory of Open Access Journals (Sweden)

    CRISTIANE eKAYSER

    2015-04-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease characterized by vascular abnormalities, and cutaneous and visceral fibrosis. Serum autoantibodies directed to multiple intracellular antigens are present in more than 95% of patients and are considered a hallmark of SSc. They are helpful biomarkers for the early diagnosis of SSc and are associated with distinctive clinical manifestations. With the advent of more sensitive, multiplexed immunoassays, new and old questions about the relevance of autoantibodies in SSc are emerging. In this review we discuss the clinical relevance of autoantibodies in SSc emphasizing the more recently published data. Moreover, we will summarize recent advances regarding the stability of SSc autoantibodies over the course of disease, whether they are mutually exclusive and their potential roles in the disease pathogenesis.

  20. Selected methods of rehabilitation in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Agnieszka Gerkowicz

    2017-09-01

    Full Text Available Systemic sclerosis is a chronic connective tissue disease characterized by microvascular abnormalities, immune disturbances and progressive fibrosis of the skin and internal organs. Skin involvement may result in contractures, leading to marked loss of hand mobility, adversely affecting the performance of daily activities and decreasing the quality of life. Face involvement not only causes functional loss, but also lowers the self-esteem of patients. Increasing attention has recently been focused on the need to rehabilitate patients with systemic sclerosis in order to prevent the development of joint contractures and loss of mobility. The study presents a review of the current literature on rehabilitation possibilities in patients with systemic sclerosis, with a special focus on physiotherapy methods.

  1. Systemic sclerosis in a patient with pityriasis rubra pilaris | Frikha ...

    African Journals Online (AJOL)

    Pityriasis rubra pilaris (PRP) is a rare, chronic erythematous squamous disorder of unknown etiology. It has been found in association with several autoimmune diseases, including thyroiditis, myositis, myasthenia gravis and vitiligo. Herein we report a case of systemic sclerosis in a patient with classic adult pityriasis rubra ...

  2. Clinical prediction of 5-year survival in systemic sclerosis

    DEFF Research Database (Denmark)

    Fransen, Julie Munk; Popa-Diaconu, D; Hesselstrand, R

    2011-01-01

    Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accura...

  3. Systemic Vasculitis During the Course of Systemic Sclerosis

    Science.gov (United States)

    Quéméneur, Thomas; Mouthon, Luc; Cacoub, Patrice; Meyer, Olivier; Michon-Pasturel, Ulrique; Vanhille, Philippe; Hatron, Pierre-Yves; Guillevin, Loïc; Hachulla, Eric

    2013-01-01

    Abstract Although the presence of antineutrophil cytoplasmic antibodies (ANCA) has been reported in patients with systemic sclerosis (SSc), the association of SSc and systemic vasculitis has rarely been described. We obtained information on cases of systemic vasculitis associated with SSc in France from the French Vasculitis Study Group and all members of the French Research Group on Systemic Sclerosis. We identified 12 patients with systemic vasculitis associated with SSc: 9 with ANCA-associated systemic vasculitis (AASV) and 3 with mixed cryoglobulinemia vasculitis (MCV). In all AASV patients, SSc was of the limited type. The main complication of SSc was pulmonary fibrosis. Only 2 patients underwent a D-penicillamine regimen before the occurrence of AASV. The characteristics of AASV were microscopic polyangiitis (n = 7) and renal limited vasculitis (n = 2). Anti-myeloperoxidase antibodies were found in 8 of the 9 patients. The Five Factor Score was above 1 in 3 of the 9 patients. Of the 3 patients with MCV, Sjögren syndrome was confirmed in 2. We compared our findings with the results of a literature review (42 previously reported cases of AASV with SSc). Although rare, vasculitis is a complication of SSc. AASV is the most frequent type, and its diagnosis can be challenging when the kidney is injured. Better awareness of this rare association could facilitate earlier diagnosis and appropriate management to reduce damage. PMID:23263715

  4. One year in review 2017: systemic sclerosis.

    Science.gov (United States)

    Barsotti, Simone; Bruni, Cosimo; Orlandi, Martina; Della Rossa, Alessandra; Marasco, Emiliano; Codullo, Veronica; Guiducci, Serena

    2017-01-01

    Systemic sclerosis is a rare acquired systemic disease characterised by heterogeneous evolution and outcome. Each year novel insights into the pathogenesis, diagnosis and treatment of this severe disease have been published. We herewith provide our overview of the most significant literature contributions published over the last year.

  5. Fructose Malabsorption in Systemic Sclerosis

    Science.gov (United States)

    Marie, Isabelle; Leroi, Anne-Marie; Gourcerol, Guillaume; Levesque, Hervé; Ménard, Jean-François; Ducrotte, Philippe

    2015-01-01

    Abstract The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal

  6. The prevalence of median neuropathy at wrist in systemic sclerosis patients at Srinagarind Hospital

    Directory of Open Access Journals (Sweden)

    Thanaporn Nimitbancha

    2015-01-01

    Full Text Available Objectives: To determine the prevalence and factor related with median neuropathy at wrist (MNW in systemic sclerosis patients. Study Design: Cross-sectional study. Setting: Srinagarind Hospital, Khon Kaen, Thailand. Participants: Systemic sclerosis patients who attended the Scleroderma Clinic, Srinagarind Hospital. Materials and Methods: Seventyfive systemic sclerosis patients were prospectively evaluated by questionnaire, physical examination, and electrodiagnostic study. The questionnaire consisted of the symptoms, duration, and type of systemic sclerosis. The physical examination revealed skin score of systemic sclerosis, pinprick sensation of median nerve distribution of both hands, and weakness of both abductor pollicis brevis muscles. The provocative test which were Tinel′s sign and Phalen′s maneuver were also examined. Moreover, electrodiagnostic study of the bilateral median and ulnar nerves was conducted. Results: The prevalence of MNW in systemic sclerosis patients was 44% - percentage of mild, moderate, and severe were 28%, 9.3%, and 6.7%, respectively. The prevalence of asymptomatic MNW was 88%. There were no association between the presence of MNW and related factors of systemic sclerosis. Conclusions: MNW is one of the most common entrapment neuropathies in systemic sclerosis patients. Systemic sclerosis patients should be screened for early signs of MNW.

  7. Development of systemic lupus erythematosus in-patient with systemic sclerosis

    International Nuclear Information System (INIS)

    Martinez, Jose B; Medina, Yimmy F; Restrepo, Jose Felix; Rondon, Federico; Iglesias G, Antonio

    2005-01-01

    A 56 years old woman with systemic sclerosis consult by rapidly progressive deterioration of his pulmonary and renal function developing a superposition syndrome with systemic lupus erythematosus, unusual presentation that respond to high doses of corticosteroid and ciclophos- phamide. This is the first reported case in the literature of a superposition syndrome that begins with systemic sclerosis. The clinical finding, immunologic profile and its possible association are discussed

  8. Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Iman A. Hassan

    2010-04-01

    Full Text Available Background: Systemic Sclerosis (SSc is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of study: To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and methods: Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results: Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P , 0.05. A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P , 0.001 and the resistive index of the main renal artery (r = 0.42, P , 0.05. Conclusion: Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher

  9. Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Reem A. Habeeb

    2010-01-01

    Full Text Available Background Systemic Sclerosis (SSc is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of Study To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and Methods Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P < 0.05. A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P < 0.001 and the resistive index of the main renal artery (r = 0.42, P < 0.05. Conclusion Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher risk of

  10. The treatment of skin ulcers in patients with systemic sclerosis

    OpenAIRE

    M. Matucci- Cerinic; F. Braschi; A. Moggi Pignone; L. Amanzi; G. Fiori

    2011-01-01

    Systemic Sclerosis (Ssc) is a complex disease of the connective tissue, characterized by progressive thickening and fibrosis of the skin and the internal organs and by diffused damage of the microvascular system. The fibrosis ones of the skin associated to the characteristic vascular alterations lead to the genesis of ulcers, more or less extended, often multiple, peripheral localization, chronic course, painful, able to influence patient’s quality of life. Indeed, immunity reactivity, the th...

  11. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

    Science.gov (United States)

    Bossini-Castillo, Lara; Martin, Jose-Ezequiel; Broen, Jasper; Gorlova, Olga; Simeón, Carmen P.; Beretta, Lorenzo; Vonk, Madelon C.; Luis Callejas, Jose; Castellví, Ivan; Carreira, Patricia; José García-Hernández, Francisco; Fernández Castro, Mónica; Coenen, Marieke J.H.; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Koeleman, Bobby P.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Palm, Øyvind; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Scorza, Raffaella; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Tan, Filemon K.; Arnett, Frank C.; Agarwal, Sandeep K.; Assassi, Shervin; Fonseca, Carmen; Mayes, Maureen D.; Radstake, Timothy R.D.J.; Martin, Javier

    2012-01-01

    A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [PMH= 1.92 × 10−5 odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH= 4.84 × 10−3 OR = 1.12). The second follow-up phase confirmed this finding (Pχ2 = 2.82 × 10−4 OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (PMH= 2.82 × 10−9 OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis. PMID:22076442

  12. Gastrointestinal transit in patients with systemic sclerosis.

    Science.gov (United States)

    Fynne, Lotte; Worsøe, Jonas; Gregersen, Tine; Schlageter, Vincent; Laurberg, Søren; Krogh, Klaus

    2011-10-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and collagen deposits. Gastrointestinal symptoms of SSc, including abdominal pain, bloating and discomfort, are common but diffuse and their pathophysiology remains obscure. To investigate the pathophysiology of abdominal pain and discomfort in individuals with SSc. A total of 15 individuals with SSc (13 women, median age 58 years), all suffering from diffuse abdominal symptoms, and 17 healthy volunteers (12 women, median age 52 years) were evaluated with the Motility Tracking System, MTS-1, measuring gastric emptying (GE) and velocity through the small intestine. SSc patients were also examined for bacterial overgrowth using the hydrogen breath test and with radiopaque markers to determine the total gastrointestinal transit time (GITT). Assessed with the MTS-1, the velocity through the proximal small intestine was significantly reduced in SSc patients (median 0.525 m/h, range 0.11-1.15) when compared to healthy subjects (median 0.91 m/h, range 0.51-1.74) (p = 0.02). Prolonged GE was found in 4 SSc patients (27%) but in none of the healthy volunteers (p = 0.04). Only 3 SSc patients (21%) had positive breath tests for small intestinal bacterial overgrowth. GITT was >3 days in 8 patients (53%). Slow small intestinal transit was associated with a prolonged GITT (p < 0.05). Velocity through the small intestine is significantly reduced in SSc patients with diffuse abdominal symptoms.

  13. Multiple Sclerosis: Evaluation of Purine Nucleotide Metabolism in Central Nervous System in Association with Serum Levels of Selected Fat-Soluble Antioxidants

    OpenAIRE

    Kuračka, Ľubomír; Kalnovičová, Terézia; Kucharská, Jarmila; Turčáni, Peter

    2014-01-01

    In the pathogenesis of demyelinating diseases including multiple sclerosis (MS) an important role is played by oxidative stress. Increased energy requirements during remyelination of axons and mitochondria failure is one of the causes of axonal degeneration and disability in MS. In this context, we analyzed to what extent the increase in purine catabolism is associated with selected blood lipophilic antioxidants and if there is any association with alterations in serum levels of coenzyme Q10....

  14. Systemic sclerosis: a world wide global analysis.

    Science.gov (United States)

    Coral-Alvarado, Paola; Pardo, Aryce L; Castaño-Rodriguez, Natalia; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel

    2009-07-01

    The objective of this study was to analyze epidemiological tendencies of systemic sclerosis (SSc) around the world in order to identify possible local variations in the presentation and occurrence of the disease. A systematic review of the literature was performed through electronic databases using the keywords "Systemic Sclerosis" and "Clinical Characteristics." Out of a total of 167 articles, 41 were included in the analysis. Significant differences in the mean age at the time of diagnosis, subsets of SSc, clinical characteristics, and presence of antibodies were found between different regions of the word. Because variations in both additive and nonadditive genetic factors and the environmental variance are specific to the investigated population, ethnicity and geography are important characteristics to be considered in the study of SSc and other autoimmune diseases.

  15. [Large vessels vasculopathy in systemic sclerosis].

    Science.gov (United States)

    Tejera Segura, Beatriz; Ferraz-Amaro, Iván

    2015-12-07

    Vasculopathy in systemic sclerosis is a severe, in many cases irreversible, manifestation that can lead to amputation. While the classical clinical manifestations of the disease have to do with the involvement of microcirculation, proximal vessels of upper and lower limbs can also be affected. This involvement of large vessels may be related to systemic sclerosis, vasculitis or atherosclerotic, and the differential diagnosis is not easy. To conduct a proper and early diagnosis, it is essential to start prompt appropriate treatment. In this review, we examine the involvement of large vessels in scleroderma, an understudied manifestation with important prognostic and therapeutic implications. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  16. Esophageal transit scintigraphy in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Marek Chojnowski

    2016-11-01

    Full Text Available Systemic sclerosis is a rare connective tissue disease, distinctive features of which are fibrosis and microangiopathy. The esophagus is one of the most commonly involved internal organs. Most patients experience dysphagia, difficulties in swallowing and gastro-esophageal reflux. However, in up to one third of cases, the initial onset of esophageal disease may be clinically silent. There are several diagnostic modalities available for assessing both morphological and functional abnormalities of the esophagus. If structural abnormalities are suspected, endoscopy is the method of choice. Functional evaluation is best achieved with manometry. Both endoscopy and manometry are invasive techniques, with low patient acceptance. Barium-contrast study is well tolerated, but qualitative assessment of functional abnormalities is imprecise. Esophageal scintigraphy is an easy, non-invasive, sensitive and specific diagnostic modality. It can detect esophageal dysfunction even in asymptomatic patients. In patients already diagnosed with systemic sclerosis, scintigraphy is useful in evaluating severity and progression of the disease.

  17. Systemic sclerosis, birth order and parity.

    Science.gov (United States)

    Russo, Paul A J; Lester, Susan; Roberts-Thomson, Peter J

    2014-06-01

    A recent study identified increasing birth order to be a risk factor for the development of systemic sclerosis (SSc). This finding supports the theory that transplacental microchimerism may be a key pathological event in the initiation of SSc. We investigated the relationship between birth order and parity and the age of onset of SSc in South Australia. A retrospective analysis of patient data in the South Australian Scleroderma Register was performed. Data were obtained from a mailed questionnaire. Control data was collected prospectively using a similar questionnaire. The relationship between birth order, family size or parity and risk of subsequent development of SSc was analyzed by mixed effects logistic regression analysis. Three hundred and eighty-seven index probands were identified and compared with 457 controls. Controls were well matched for gender, but not for age. No statistically significant relationship was identified between SSc and birth order, parity in females, family size, age at first pregnancy in females or gender of first child in parous females. Our data suggests that parity, age at first pregnancy and the gender of the first child are not relevant factors in our understanding of the epidemiology and pathogenesis of SSc. Birth order and family size in both genders also appears irrelevant. These results argue against microchimerism as being relevant in the pathogenesis of SSc and add further support to the theory that stochastic events may be important in the etiopathogenesis of SSc. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  18. Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

    Directory of Open Access Journals (Sweden)

    Andréa Tavares Dantas

    2016-01-01

    Full Text Available Objective. To determine active TGF-β1 (aTGF-β1 levels in serum, skin, and peripheral blood mononuclear cell (PBMC culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC. In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001. Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p = 0.02, digital ulcers (p = 0.02, lung fibrosis (p < 0.0001, positive antitopoisomerase I (p = 0.03, and higher modified Rodnan score (p = 0.046. Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

  19. Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Avner Meoded

    2013-08-01

    Full Text Available Introduction: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS, but it has not been well studied in primary lateral sclerosis (PLS. The aims of this study were to (1 compare cognitive function in PLS to that in ALS patients, (2 explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI metrics of white matter tracts and gray matter volumes, and (3 compare DTI metrics in patients with and without cognitive and behavioral changes. Methods: The Delis-Kaplan Executive Function System (D-KEFS, the Mattis Dementia Rating Scale (DRS-2, and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results: More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment.

  20. Experimentally-derived fibroblast gene signatures identify molecular pathways associated with distinct subsets of systemic sclerosis patients in three independent cohorts.

    Directory of Open Access Journals (Sweden)

    Michael E Johnson

    Full Text Available Genome-wide expression profiling in systemic sclerosis (SSc has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like, each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a compendium of microarray datasets consisting of skin biopsies from three independent cohorts representing 80 SSc patients, 4 morphea, and 26 controls. IFNα signaling showed a strong association with early disease, while TGFβ signaling spanned the fibroproliferative and inflammatory subsets, was associated with worse MRSS, and was higher in lesional than non-lesional skin. The fibroproliferative subset was most strongly associated with PDGF signaling, while the inflammatory subset demonstrated strong activation of innate immune pathways including TLR signaling upstream of NF-κB. The limited and normal-like subsets did not show associations with fibrotic and inflammatory mediators such as TGFβ and TNFα. The normal-like subset showed high expression of genes associated with lipid signaling, which was absent in the inflammatory and limited subsets. Together, these data suggest a model by which IFNα is involved in early disease pathology, and disease severity is associated with active TGFβ signaling.

  1. The role of klotho in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    R. Talotta

    2017-12-01

    Full Text Available The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc, through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan’s Skin Score, Medsger’s scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8 years and 77 healthy controls (28 females, mean age 49.7±10.2 years. In the group of SSc patients, 19 (27.5% suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine. The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001. However, Spearman’s test showed no significant association between klotho serum levels and disease activity, concerning either clinical, laboratory or instrumental findings. Our data show a significant deficit of klotho in SSc patients although any significant association was detected between klotho serum concentration and the clinical, laboratory or instrumental features of the disease. However, due to the limits of the study, further investigations are required.

  2. Work productivity in systemic sclerosis, its economic burden and association with health-related quality of life.

    Science.gov (United States)

    Morrisroe, Kathleen; Sudararajan, Vijaya; Stevens, Wendy; Sahhar, Joanne; Zochling, Jane; Roddy, Janet; Proudman, Susanna; Nikpour, Mandana

    2018-01-01

    To evaluate work productivity and its economic burden in SSc patients. Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study were mailed questionnaires assessing employment (Workers' Productivity and Activity Impairment Questionnaire and a custom-made questionnaire) and health-related quality of life (HRQoL) (36-item Short Form Health Survey and Patient-Reported Outcomes Measurement Information System 29). Linear regression methods were used to determine factors associated with work productivity. Among 476 patients submitting responses, 55.2% productivity while at work (presenteeism) accounted for 22% of their working week. Annual costs per patient as a consequence of unemployment and reduced productivity equated to a total of AUD$67 595.40. Factors independently associated with reduced work productivity were presence of synovitis and sicca symptoms, while tertiary education protected against work impairment. Patients with low HRQoL scores also had low work productivity. SSc is associated with considerable unemployment and reduced productivity, which in turn is associated with a substantial economic burden and poor HRQoL. Raising awareness and identifying modifiable factors are possible ways of reducing this burden. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Early- versus Late-Onset Systemic Sclerosis

    Science.gov (United States)

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  4. PROSPECTS FOR USING TOCILIZUMAB IN SYSTEMIC SCLEROSIS

    Directory of Open Access Journals (Sweden)

    L. P. Ananyeva

    2015-01-01

    Full Text Available Interleukin 6 (IL-6 is one of the key cytokines that are involved in inflammation and that has pleiotropic properties. Diverse effects of IL-6 result from the transmission of an intracellular signal in two ways: via direct binding to a membrane receptor having a molecular mass of 80 kDA (a classical way or absorption of the IL-6 complex with its soluble receptor on another transmembrane receptor – gp-130 (trans-signaling. Different signaling pathways lead to various consequences. The classical way of signal transmission activates mainly protective and regenerative processes; trans-signaling has a proinflammatory potential. The review gives schemes of signal stimuli and shows that IL-6 and its receptors are a dynamic intricately organized regulatory system that can adapt to stress-induced homeostatic changes. It considers in detail evidence suggesting the effect of IL-6 on the development and maintenance of a number of systemic sclerosis (SS-specific pathogenetic disorders, such as the activation of the endothelium, the development and maintenance of inflammation, and excessive deposition of extracellular matrix components in tissues. Endothelial cell activation during trans-signaling gives rise to an enhanced adhesion molecule expression, chemokine release, and further production of IL-6. Excessive secretion of the latter may initiate a fibrosing process and favor the further development of pathologicalconditions. Autoimmune disorders theoretically associated with IL-6 overproduction occur in SS. Elevated blood IL-6 concentrations in SS are related to disease clinical parameters, such as activity, severity, worse prognosis, and reduced survival. Taken together, the data presented suggest that IL-6 blocking may have a therapeutic potential in SS. The first clinical data on successfully using the IL-6 receptor antagonist tocilizumab to treat SS are given.

  5. Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

    Science.gov (United States)

    Huang, Xiao-Lei; Wu, Guo-Cui; Wang, Yu-Jie; Yang, Xiao-Ke; Yang, Guo-Jun; Tao, Jin-Hui; Duan, Yu; Yan, Jun-Wei; Li, Xiang-Pei; Ye, Dong-Qing; Wang, Jing

    2016-08-01

    The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

  6. Capillaroscopy 2016: new perspectives in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Carmen Pizzorni

    2016-01-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disorder of unknown aetiology characterized by early impairment of the microvascular system. Nailfold microangiopathy and decreased peripheral blood perfusion are typical clinical aspects of SSc. The best method to evaluate vascular injury is nailfold videocapillaroscopy, which detects peripheral capillary morphology, and classifies and scores the abnormalities into different patterns of microangiopathy. Microangiopathy appears to be the best evaluable predictor of the disease development and has been observed to precede the other symptoms by many years. Peripheral blood perfusion is also impaired in SSc, and there are different methods to assess it: laser Doppler and laser speckle techniques, thermography and other emerging techniques.

  7. Selective association of multiple sclerosis with infectious mononucleosis

    NARCIS (Netherlands)

    Zaadstra, B.M.; Chorus, A.M.J.; Buuren, S. van; Kalsbeek, H.; Noort, J.M. van

    2008-01-01

    Previous studies have suggested an association between multiple sclerosis (MS) and infectious mononucleosis (IM) but data on the exact strength of this association or its selectivity have been conflicting. In this study we have evaluated the association between MS and a variety of common childhood

  8. Infectious mononucleosis and multiple sclerosis - Updated review on associated risk.

    Science.gov (United States)

    Sheik-Ali, Sharaf

    2017-05-01

    There has been substantial evidence accumulating on the role of infectious mononucleosis (IM) and the subsequent risk of obtaining Multiple Sclerosis (MS). Up to date studies not previously explored were reviewed by the author to further clarify the association. Medline and Web of Science were searched with no time constraints for articles exploring an association between Multiple Sclerosis and Infectious Mononucleosis. 24 articles were found, totalling 1063 cases and 13,227 cohort/controls. 23/24 (96%) articles reported a significant association of Infectious Mononucleosis on the risk of subsequent multiple sclerosis. Overall, new literature on IM and risk of MS categorically supports the association. Future work should focus on other risk factors such as age and gender on IM and subsequent risk of MS. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  9. Clinical presentation in patients with systemic sclerosis

    International Nuclear Information System (INIS)

    Silvarino, R.; Rebella, M.; Alonso, J.; Cairoli, E.

    2009-01-01

    Introduction: systemic sclerosis is an autoimmune disease characterized by endothelial damage, and skin, vessel and internal organ fibrosis and inflammation. There are differences in terms of frequency, severity and prognosis for the different ethnic groups, what reinforces the importance of the study in each geographical region with the purpose of enabling early diagnosis of its incipient symptoms.Methods: we conducted a descriptive and retrospective study form March 2006 through March 2008, including patients with a final diagnosis of systemic sclerosis, who are treated at the Systemic Autoimmune Diseases Unit at the Clinicas Hospital. Results: 31 women were included in the study, average follow-up of patients was 39.2 months, and average age at the time of diagnosis was 47.6 years. Eleven patients (35,5) presented diffuse disease and 20 (64.5) of them evidenced limited disease. Thirty patients presented Raynaud's phenomenon. In 92 of cases capilaroscopy showed a sclerodermiform pattern. In terms of the respiratory system, we found interstitial pathology in 25 of cases, pulmonary arterial hypertension in 22.2 and are restrictive pattern in respiratory function studies in 35.5. Also, 67.7 presented digestive manifestations and 9.6 developed sclerodermic renal crisis. We found anti-nuclear antibodies (ANA) in 29 out of 31 patients (93,5) patients; 16 presented anticentromere antibodies and five anti-topoisomerasa-I antibodies. The four patients (12.9)who died during follow-up presented common elements such as diffuse sclerosis, digital ulcers and severe respiratory compromise. Conclusions: the clinical and immune characteristics found in our study were similar to those described in other series. Should there be no specific treatment, it is essential to perform regular assessment of visceral impact in order to control and delay complications which result in high morbimortality rates. (author) [es

  10. Abnormalities of small bowel and colon in systemic sclerosis

    International Nuclear Information System (INIS)

    Scutellari, P.N.; Cinotti, A.; Cavallari, L.; Orzincolo, C.; Dovigo, L.; Trotta, F.; Menegale, G.

    1990-01-01

    A series of 21 subjects (2 males and 19 females) affected with systemic sclerosis, was examined by small bowel (oral and intubation methods) and colon enema. The underlying process responsible for abnormalities in the small bowel and colon in systemic sclerosis is a variable and pacthy destruction of the muscularis propria, that produces the structural and functional changes detected on X-ray: Pathologic condition is the same affecting the esophagus. The scout film of the abdomen often reveals colonic distension and fecal impaction, so that it may be quite difficult to prepare adequately the patients for a barium enema. Peristalsis may be virtually absent in short segments, and transit time may be several time longer than that in normal patients. For these reasons, intestinal pseudo-obstruction may appear in systemic sclerosis. The observed radiographic changes are: 1) in the small bowel: a) dilatation of the gut, especially in its proximal portions (duodenum and jejunum), in which the valvulae conniventes are straightened, normal or thinned; b) presence of diverticula, 2-4 cm in diameter, with hemispherical shape without the neck-like opening into the bowel lumen; 2) in the colon, the characteristic finding is an increase in size of individual haustra, forming sacculations or pseudo-diverticula, usually on the antemesenteric border of the transverse colon, better demonstrated on post-evacuation film. Moreover, loss of colonic haustration is also observed associated to colonic elongation and dilatation

  11. MDCT imaging of calcinosis in systemic sclerosis

    International Nuclear Information System (INIS)

    Freire, V.; Becce, F.; Feydy, A.; Guérini, H.; Campagna, R.; Allanore, Y.; Drapé, J.-L.

    2013-01-01

    Calcinosis is a typical feature of systemic sclerosis (SSc) and can be found in many different tissues including the superficial soft tissues, periarticular structures, muscles, and tendons. It can also provoke erosive changes on bones. Investigation is conducted most often with plain radiographs. However, when a more detailed assessment is necessary, multidetector computed tomography (MDCT) is helpful owing to its multiplanar reformat (MPR) ability. The purpose of this review is to provide an overview of the various appearances of calcinosis in SSc patients as visualized at MDCT

  12. Environmental Mycobiome Modifiers of Inflammation and Fibrosis in Systemic Sclerosis

    Science.gov (United States)

    2016-09-01

    autoimmune systemic sclerosis and cancer: disease stratification, co-expression networks and genetic polymorphisms” Cancer Mechanisms Program, Norris ...NOTES 14. ABSTRACT This project is focused on Systemic Sclerosis (SSc), a progressive fibrotic disease characterized by skin fibrosis and damage to...quantitative manner. Our studies suggest that disease pathogenesis includes a common environmental fungal trigger, Rhodotorula glutinis, which we

  13. A rare association of localized gigantism with tuberous sclerosis.

    Science.gov (United States)

    Reddy, B S; Sheriff, M O; Garg, B R; Ratnakar, C

    1992-10-01

    An unusual association of localized gigantism with hypertrophy of the long bones and soft tissues in the left lower limb in an 18-year-old male with tuberous sclerosis (TS) is reported. The significance of this association is discussed from the point of view of its common neural crest origin during embryogenesis.

  14. Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

    Science.gov (United States)

    Lee, Jason J; Pope, Janet E

    2016-02-01

    Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

  15. Brain magnetic resonance imaging findings in patients with systemic sclerosis.

    Science.gov (United States)

    Mohamed, Reem H A; Nassef, Amr A

    2010-02-01

    Systemic sclerosis is a multisystem disease where functional and structural abnormalities of small blood vessels prevail. Recently, transient ischemic attacks, ischemic stroke, and hemorrhages have been reported as primary consequence of vascular central nervous system affection in systemic sclerosis. Magnetic resonance imaging (MRI) is considered to be the most sensitive diagnostic technique for detecting symptomatic and asymptomatic lesions in the brain in cases of multifocal diseases. Evaluate brain changes in patients with systemic sclerosis using MRI. Thirty female patients with systemic sclerosis aged 27-61 years, with disease duration of 1-9 years and with no history of other systemic disease or cerebrovascular accidents, were enrolled. An age-matched female control group of 30 clinically normal subjects, underwent brain MR examination. Central nervous system involvement in the form of white matter hyperintense foci of variable sizes were found in significantly abundant forms in systemic sclerosis patients on MR evaluation than in the age-related control group, signifying a form of central nervous system vasculopathy. Such foci showed no definite correlation with disease duration, yet they showed significant correlation to severity of peripheral vascular disease, headaches, fainting attacks and depression in the group under study. Asymptomatic as well as symptomatic central nervous system ischemic vasculopathy is not uncommon in systemic sclerosis patients and MRI is considered a sensitive noninvasive screening tool for early detection of CNS involvement in patients with systemic sclerosis.

  16. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-01-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...... cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might...

  17. [Cognitive function in patients with systemic sclerosis].

    Science.gov (United States)

    Straszecka, J; Jonderko, G; Kucharz, E J; Brzezińska-Wcisło, L; Kotulska, A; Bogdanowski, T

    1997-09-01

    Central nervous system involvement is seldom reported in patients with systemic sclerosis (SSc). Cognitive functions were determined in 21 patients with definite SSc and 42 healthy controls. Thyroid function was also measured in order to eliminate the effect of hypothyroidism on cognitive functioning. It was found that the SSc patients with normal thyroid function showed defective long-term and recent memory, learning ability, criticism, perception and visuo-perceptual skills, their simple reaction time was prolonged. Similar but less advanced cognitive defects were shown in the SSc patients with overt or latent hypothyroidism. The obtained results indicate that the central nervous system involvement is more common in patients with SSc than it has been reported earlier.

  18. Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study

    DEFF Research Database (Denmark)

    Peytrignet, Sébastien; Denton, Christopher P; Lunt, Mark

    2018-01-01

    Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HA...

  19. A proposal of criteria for the classification of systemic sclerosis.

    Science.gov (United States)

    Nadashkevich, Oleg; Davis, Paul; Fritzler, Marvin J

    2004-11-01

    Sensitive and specific criteria for the classification of systemic sclerosis are required by clinicians and investigators to achieve higher quality clinical studies and approaches to therapy. A clinical study of systemic sclerosis patients in Europe and Canada led to a set of criteria that achieve high sensitivity and specificity. Both clinical and laboratory investigations of patients with systemic sclerosis, related conditions and diseases with clinical features that can be mistaken as part of the systemic sclerosis spectrum were undertaken. Laboratory investigations included the detection of autoantibodies to centromere proteins, Scl-70 (topoisomerase I), and fibrillarin (U3-RNP). Based on the investigation of 269 systemic sclerosis patients and 720 patients presenting with related and confounding conditions, the following set of criteria for the classification of systemic sclerosis was proposed: 1) autoantibodies to: centromere proteins, Scl-70 (topo I), fibrillarin; 2) bibasilar pulmonary fibrosis; 3) contractures of the digital joints or prayer sign; 4) dermal thickening proximal to the wrists; 5) calcinosis cutis; 6) Raynaud's phenomenon; 7) esophageal distal hypomotility or reflux-esophagitis; 8) sclerodactyly or non-pitting digital edema; 9) teleangiectasias. The classification of definite SSc requires at least three of the above criteria. Criteria for the classification of systemic sclerosis have been proposed. Preliminary testing has defined the sensitivity and specificity of these criteria as high as 99% and 100%, respectively. Testing and validation of the proposed criteria by other clinical centers is required.

  20. Limited Mouth Opening Secondary to Diffuse Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Tomoko Wada

    2013-01-01

    Full Text Available Systemic sclerosis (SSc is a relatively rare condition with an immunologically mediated pathogenesis. For reasons that are not clearly understood, dense collagen is deposited in the connective tissues of the body in extraordinary amounts. Although its dramatic effects are seen in association with the skin, the disease is often quite serious with visceral organ involvement. We describe a case of limited mouth opening secondary to diffuse SSc, improvement in mouth opening with passive jaw stretch exercises, and the challenges involved in performing dental procedures for such patients.

  1. Amyotrophic lateral sclerosis associated with pregnancy.

    LENUS (Irish Health Repository)

    Tyagi, A

    2012-02-03

    Amyotrophic lateral sclerosis (ALS) is the most common, progressive motor neurone disease but is rare in the obstetric population. Only 4 cases have been described in the English literature since 1975. We describe a 29 year old woman who presented with ataxia, lower limb weakness and dysarthria 4 weeks after the birth of her first child. The symptoms had onset during the pregnancy but had not been considered remarkable. There were clinical features of upper and lower motor neurone involvement without any sensory loss. MRI of brain and spine was normal. CSF analysis was negative. EMG studies confirmed the presence of widespread anterior horn cell dysfunction compatible with ALS. The patient was commenced on Riluzole and has progressed clinically, at 12 months post diagnosis.

  2. Work Disability in Early Systemic Sclerosis

    DEFF Research Database (Denmark)

    Sandqvist, Gunnel; Hesselstrand, Roger; Petersson, Ingemar F

    2015-01-01

    OBJECTIVE: To study work disability (WD) with reference to levels of sick leave and disability pension in early systemic sclerosis (SSc). METHODS: Patients with SSc living in the southern part of Sweden with onset of their first non-Raynaud symptom between 2003 and 2009 and with a followup of 36...... months were included in a longitudinal study. Thirty-two patients (26 women, 24 with limited SSc) with a median age of 47.5 years (interquartile range 43-53) were identified. WD was calculated in 30-day intervals from 12 months prior to disease onset until 36 months after, presented as the prevalence...... of WD per year (0-3) and as the period prevalence of mean net days per month (± SD). Comparisons were made between patients with different disease severity and sociodemographic characteristics, and between patients and a reference group (RG) from the general population. RESULTS: Seventy-eight percent...

  3. Gastric emptying abnormalities in progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Sridhar, K.; Magyar, L.; Lange, R.; McCallum, R.W.

    1985-01-01

    The authors studied gastric emptying (GE) in patients with peripheral manifestations of progressive systemic sclerosis (PSS) using a radionuclide method. 18 patients underwent esophageal manometry and a GE study using chicken liver labeled in vivo with Tc-99m sulfur colloid as a marker of solid emptying. GE was also measured in 13 normal volunteers. 4 PSS patients with normal esophageal motility also had normal GE. The GE of 14 PSS patients with abnormal esophageal motility was significantly (p < 0.05) delayed; with 67.4% retention of isotope after 2 hours compared to 49.8 in normals. The authors conclude that GE of solids is slow in approximately 2/3 of PSS patients with abnormal esophageal motility but is normal if the esophagus is uninvolved; Delayed GE may contribute to the severity of gastroesophageal reflux in PSS patients and the degree of dysphasgia; and Metoclopramide accelerates GE in PSS patients and should have a valuable therapeutic role

  4. D-penicillamine in systemic sclerosis? Yes!

    Science.gov (United States)

    Medsger, T A; Lucas, M; Wildy, K S; Baker, C

    2001-01-01

    The use of D-penicillamine in systemic sclerosis (SSc) has been controversial. We have reviewed the major published studies on this drug in SSc with diffuse cutaneous (dc) involvement and summarized our own recent experience in dcSSc patients treated with and without D-penicillamine. We conclude that D-penicillamine favourably alters the natural history of skin involvement in dcSSc, even when used in low dose. Furthermore, recurrence of diffuse skin change after discontinuation of D-penicillamine and improvement in skin thickening after reinitiation of the drug support its effectiveness. We believe that the rheumatologic community should use D-penicillamine in patients with early dcSSc.

  5. Adenocarcinoma do pulmão em doente com esclerodermia: Um caso clínico Lung adenocarcinoma associated with systemic sclerosis: A case report

    Directory of Open Access Journals (Sweden)

    João Bento

    2009-01-01

    Full Text Available A esclerodermia é uma doença do tecido conjuntivo de etiologia desconhecida, que tem sido associada a um risco acrescido de malignidade. O cancro do pulmão é a neoplasia mais frequente, nestes doentes. Apresenta-se o caso clínico de uma mulher de 42 anos, não fumadora, com esclerodermia, que desenvolveu agravamento progressivo do seu estado geral e derrame pleural com características de exsudado, sem evidência de infecção ou malignidade. A TAC torácica mostrou zonas de fibrose, a broncofibroscopia, os lavados brônquico e broncoalveolar foram normais. Foi excluída neoplasia extrapulmonar. Na pleuroscopia, observaram-se formações nodulares, cujas biópsias revelaram tratar-se de adenocarcinoma pulmonar. Iniciou quimioterapia, desenvolvendo ao 48.º dia neutropenia febril e sépsis, vindo a morrer 12 dias depois. Salientamos este caso pela relação, apesar de rara, entre a esclerodermia e o cancro do pulmão e pela importância de uma vigilância pulmonar cuidadosa, em indivíduos com esta doença reumatológica, pelo risco acrescido de neoplasia.Systemic sclerosis (scleroderma is a connective tissue disorder of unknown aetiology characterised by immune abnormalities, which has been related to an increased risk of malignancy. Lung cancer is the most prevalent among these patients. We present a clinical case of a 42 years old non smoker female with systemic sclerosis. She presented progressive general health status worsening and an exudative pleural effusion, with no evidence of infection or malignancy. Chest high resolution computed tomography revealed pulmonary fibrosis. Bronchoscopy, bronchial and bronchoalveolar lavage were normal. Extra-pulmonary malignancies were excluded. Pleural nodularities were found on pleuroscopy and the biopsy was compatible with lung adenocarcinoma. Chemotherapy was then started, which complicated with febrile neutropenia, sepsis and patient death 12 days after. The purpose of this case report is to

  6. Validation of potential classification criteria for systemic sclerosis.

    NARCIS (Netherlands)

    Johnson, S.R.; Fransen, J.; Khanna, D.; Baron, M.; Hoogen, F. van den; Medsger TA, J.r.; Peschken, C.A.; Carreira, P.E.; Riemekasten, G.; Tyndall, A.; Matucci-Cerinic, M.; Pope, J.E.

    2012-01-01

    OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the

  7. Progressive Systemic sclerosis, manifested like malabsorption syndrome. Case report

    International Nuclear Information System (INIS)

    Ortiz Piza, Gabriel Jaime; Gonzalez Vasquez, Carlos Mario

    2005-01-01

    We report the case of a 32 year old woman whose first manifestation of systemic sclerosis was malabsorption syndrome. The small bowel series was the clue to the diagnosis, confirmed by laboratory tests and progression of the disease

  8. Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

    Directory of Open Access Journals (Sweden)

    Marta Sofia Mendes Oliveira

    2015-09-01

    Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

  9. Systemic sclerosis with normal or nonspecific nailfold capillaroscopy.

    Science.gov (United States)

    Fichel, Fanny; Baudot, Nathalie; Gaitz, Jean-Pierre; Trad, Salim; Barbe, Coralie; Francès, Camille; Senet, Patricia

    2014-01-01

    In systemic sclerosis (SSc), a specific nailfold videocapillaroscopy (NVC) pattern is observed in 90% of cases and seems to be associated with severity and progression of the disease. To describe the characteristics of SSc patients with normal or nonspecific (normal/nonspecific) NVC. In a retrospective cohort study, clinical features and visceral involvements of 25 SSc cases with normal/nonspecific NVC were compared to 63 SSc controls with the SSc-specific NVC pattern. Normal/nonspecific NVC versus SSc-specific NVC pattern was significantly associated with absence of skin sclerosis (32 vs. 6.3%, p = 0.004), absence of telangiectasia (47.8 vs. 17.3%, p = 0.006) and absence of sclerodactyly (60 vs. 25.4%, p = 0.002), and less frequent severe pulmonary involvement (26.3 vs. 58.2%, p = 0.017). Normal/nonspecific NVC in SSc patients appears to be associated with less severe skin involvement and less frequent severe pulmonary involvement. © 2014 S. Karger AG, Basel.

  10. T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

    Science.gov (United States)

    van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

    2018-05-01

    Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

  11. Unmet patient needs in systemic sclerosis.

    Science.gov (United States)

    Rubenzik, Tamara T; Derk, Chris T

    2009-04-01

    Assessment of systemic sclerosis patients has not directly addressed functioning from the patient's perspective. With this study, we aim to gain our patient's point of view by using a questionnaire to describe their unmet needs and understanding what demographic parameters influence these. A computer randomization program selected 50 patients, from 242 systemic sclerosis patients actively followed at our rheumatology clinic, to receive a survey about unmet needs. Twenty-five patients responded to the survey. Of 81 questions, 9 provided demographic data, whereas 72 questions addressed physical, daily living, psychologic, spiritual, existential, health services, health information, social support, and employment issues. A 4-point scale from no need to high need was used to rate all questions. Significant need was considered any issue for which more than 50% of patients reported a high need. The Fisher exact test was used to compare different demographic variables to unmet patient needs. The psychologic/spiritual/existential category had 9 questions reaching significance, the health services category had 5 significant questions, the physical category had 4 significant questions. Patients who had not attended college were more likely to have higher needs than patients who completed a college degree. Unmarried patients reported higher needs in 8 measures as compared with married patients, and patients in rural areas had higher needs in social support needs. The greatest prevalence of unmet needs in scleroderma patients were in the psychologic/spiritual/existential domain, such as being unable to do things they used to do, fear that the disease will worsen, anxiety and stress, feeling down or depressed, fears of physical disability, uncertainty about the future, change in appearance, keeping a positive outlook, and feeling in control. Significant differences were observed in unmet needs based on education, marital status, location, knowledge of disease, and age

  12. 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. 

  13. Chronic toxicity risk after radiotherapy for patients with systemic sclerosis (systemic scleroderma) or systemic lupus erythematosus: Association with connective tissue disorder severity

    International Nuclear Information System (INIS)

    Gold, Douglas G.; Miller, Robert C.; Pinn, Melva E.; Osborn, Thomas G.; Petersen, Ivy A.; Brown, Paul D.

    2008-01-01

    No method reliably identifies which patients with connective tissue disorders are at greatest risk of radiotherapy-related complications. Building on our prior experience, we postulated that disease severity, as measured by the number of organ systems involved, may predict chronic radiation toxicity risk

  14. Multiple sclerosis: evaluation of purine nucleotide metabolism in central nervous system in association with serum levels of selected fat-soluble antioxidants.

    Science.gov (United States)

    Kuračka, Lubomír; Kalnovičová, Terézia; Kucharská, Jarmila; Turčáni, Peter

    2014-01-01

    In the pathogenesis of demyelinating diseases including multiple sclerosis (MS) an important role is played by oxidative stress. Increased energy requirements during remyelination of axons and mitochondria failure is one of the causes of axonal degeneration and disability in MS. In this context, we analyzed to what extent the increase in purine catabolism is associated with selected blood lipophilic antioxidants and if there is any association with alterations in serum levels of coenzyme Q10. Blood serum and cerebrospinal fluid (CSF) samples from 42 patients with diagnosed MS and 34 noninflammatory neurologic patients (control group) were analyzed. Compared to control group, MS patients had significantly elevated values of all purine nucleotide metabolites, except adenosine. Serum lipophilic antioxidants γ -tocopherol, β -carotene, and coenzyme Q10 for the vast majority of MS patients were deficient or moved within the border of lower physiological values. Serum levels of TBARS, marker of lipid peroxidation, were increased by 81% in the MS patients. The results indicate that the deficit of lipophilic antioxidants in blood of MS patients may have a negative impact on bioenergetics of reparative remyelinating processes and promote neurodegeneration.

  15. Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

    Science.gov (United States)

    Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

    2017-01-01

    Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

  16. Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Antonio Lobasso

    2017-09-01

    Full Text Available BackgroundThyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc. Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4 malabsorption in patients with Hashimoto’s thyroiditis (HT and SSc.Case reportHere, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure.ConclusionA recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

  17. Peripapillar retinal hamartoma associated with tuberous sclerosis. Case report.

    Science.gov (United States)

    Hernández Pardines, F; Núñez Márquez, S; Fernández Montalvo, L; Serra Verdú, M C; Juárez Marroquí, A

    2018-03-01

    Tuberous sclerosis is a rare multisystemic disease with an autosomal dominant inheritance pattern. There are few documented cases in the literature of retinal hamartomas (astrocytomas) with aggressive progression in the context of this disease. A report is presented on a case of a 31 year-old male with unknown history of ophthalmic or systemic conditions, who referred to a history of 6 months of blurred vision in his right eye. This was caused by a unilateral retinal hamartoma due to an undiagnosed tuberous sclerosis. Multidisciplinary management, with the cooperation of Internal Medicine and the Oncology Department, is needed in these cases, as well as genetic counselling for affected patients. Complications are directly related to increased tumour size. Treatment does not seem to have any influence on the natural history of the disease. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. PRKCA and multiple sclerosis: association in two independent populations.

    Directory of Open Access Journals (Sweden)

    Janna Saarela

    2006-03-01

    Full Text Available Multiple sclerosis (MS is a chronic disease of the central nervous system responsible for a large portion of neurological disabilities in young adults. Similar to what occurs in numerous complex diseases, both unknown environmental factors and genetic predisposition are required to generate MS. We ascertained a set of 63 Finnish MS families, originating from a high-risk region of the country, to identify a susceptibility gene within the previously established 3.4-Mb region on 17q24. Initial single nucleotide polymorphism (SNP-based association implicated PRKCA (protein kinase C alpha gene, and this association was replicated in an independent set of 148 Finnish MS families (p = 0.0004; remaining significant after correction for multiple testing. Further, a dense set of 211 SNPs evenly covering the PRKCA gene and the flanking regions was selected from the dbSNP database and analyzed in two large, independent MS cohorts: in 211 Finnish and 554 Canadian MS families. A multipoint SNP analysis indicated linkage to PRKCA and its telomeric flanking region in both populations, and SNP haplotype and genotype combination analyses revealed an allelic variant of PRKCA, which covers the region between introns 3 and 8, to be over-represented in Finnish MS cases (odds ratio = 1.34, 95% confidence interval 1.07-1.68. A second allelic variant, covering the same region of the PRKCA gene, showed somewhat stronger evidence for association in the Canadian families (odds ratio = 1.64, 95% confidence interval 1.39-1.94. Initial functional relevance for disease predisposition was suggested by the expression analysis: The transcript levels of PRKCA showed correlation with the copy number of the Finnish and Canadian "risk" haplotypes in CD4-negative mononuclear cells of five Finnish multiplex families and in lymphoblast cell lines of 11 Centre d'Etude du Polymorphisme Humain (CEPH individuals of European origin.

  19. Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

    Science.gov (United States)

    Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

    2018-03-13

    Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

  20. Systemic Sclerosis and Silicone Breast Implant: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Antonios Psarras

    2014-01-01

    Full Text Available Environmentally induced systemic sclerosis is a well-recognized condition, which is correlated with exposure to various chemical compounds or drugs. However, development of scleroderma-like disease after exposure to silicone has always been a controversial issue and, over time, it has triggered spirited debate whether there is a certain association or not. Herein, we report the case of a 35-year-old female who developed Raynaud’s phenomenon and, finally, systemic sclerosis shortly after silicone breast implantation surgery.

  1. Nutritional support in patients with systemic sclerosis.

    Science.gov (United States)

    Ortiz-Santamaria, Vera; Puig, Celia; Soldevillla, Cristina; Barata, Anna; Cuquet, Jordi; Recasens, Asunción

    2014-01-01

    Systemic sclerosis (SSc) is a chronic multisystem autoimmune disease which involves the gastrointestinal tract in about 90% of cases. It may contribute to nutritional deterioration. To assess whether the application of a nutritional support protocol to these patients could improve their nutritional status and quality of life. Single center prospective study, performed on an outpatient basis, in a county hospital. The Malnutrition Universal Screening Tool (MUST) was used to screen risk for malnutrition. Health questionnaire SF-36 and the Hospital Anxiety and Depression Scale were used to assess quality of life and psychopathology respectively. Weight, height, energy and protein requirements, macronutrient intake and nutritional biochemical parameters were evaluated. Nutritional intervention was performed in patients at risk for malnutrition. Of the 72 patients, 12.5% were at risk for malnutrition. Iron deficiency anemia (18.35%) and vitamin D deficiency (54%) were the most frequently observed nutritional deficits. The questionnaires on psychopathology and quality of life showed a high prevalence of anxiety and depression, and lower level poor quality of life in the physical and mental component. No significant improvements were observed in the weight, food intake, nutritional biochemical parameters, psychopathology and quality of life follow-up. Dietary intervention was able to maintain body weight and food intake. Iron deficiency anemia and vitamin D deficiency improved with iron and vitamine D supplements. No deterioration was observed in psychological assessment or quality of life. Studies with larger numbers of patients are needed to assess the efficacy of this intervention. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  2. Interstitial Lung disease in Systemic Sclerosis

    International Nuclear Information System (INIS)

    Ooi, G.C.; Mok, M.Y.; Tsang, K.W.T.; Khong, P.L.; Fung, P.C.W.; Chan, S.; Tse, H.F.; Wong, R.W.S.; Lam, W.K.; Lau, C.S.; Wong, Y.

    2003-01-01

    Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. Material and Methods: : 45 SSc patients (40 women, 48.5±13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively

  3. L-selectin and skin damage in systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    James V Dunne

    Full Text Available L-selectin ligands are induced on the endothelium of inflammatory sites. L-selectin expression on neutrophils and monocytes may mediate the primary adhesion of these cells at sites of inflammation by mediating the leukocyte-leukocyte interactions that facilitate their recruitment. L-selectin retains functional activity in its soluble form. Levels of soluble L-selectin have been reported as both elevated and lowered in patients with systemic sclerosis (SSc. This preliminary study seeks to discern amongst these disparate results and to discover whether there is an association between L-selectin concentrations in plasma and skin damage in SSc patients.Nineteen cases with limited systemic sclerosis (lSSc and 11 cases with diffuse systemic sclerosis (dSSc were compared on a pairwise basis to age- and sex-matched controls. Criteria of the American College of Rheumatology were used to diagnose SSc. Skin involvement was assessed using the modified Rodnan skin score (mRSS. We find no association between mRSS and plasma L-selectin concentration in lSSc cases (p = 0.9944 but a statistically significant negative correlation in dSSc cases (R(2 = 73.11 per cent, p = 0.0008. The interpretation of the slope for dSSc cases is that for each increase of 100 ng/ml in soluble L-selectin concentration, the mRSS drops 4.22 (95 per cent CI: 2.29, 6.16. There was also a highly statistically significant negative correlation between sL-selectin and disease activity (p = 0.0007 and severity (p = 0.0007 in dSSc cases but not in lSSc cases (p = 0.2596, p = 0.7575, respectively.No effective treatments exist for skin damage in SSc patients. Nor is there a laboratory alternative to the modified Rodnan skin score as is the case for other organs within the body. Modulation of circulating L-selectin is a promising target for reducing skin damage in dSSc patients. Plasma levels of soluble L-selectin could serve as an outcome measure for dSSc patients in

  4. A gender gap in primary and secondary heart dysfunctions in systemic sclerosis

    DEFF Research Database (Denmark)

    Elhai, Muriel; Avouac, Jérôme; Walker, Ulrich A

    2016-01-01

    OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed...

  5. Impaired quality of life in patients with systemic sclerosis compared to the general population and chronic dermatoses

    OpenAIRE

    Bretterklieber, Agnes; Painsi, Clemens; Avian, Alexander; Wutte, Nora; Aberer, Elisabeth

    2014-01-01

    Background Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the ...

  6. Association of diffuse idiopathic skeletal hyperostosis and aortic valve sclerosis

    Directory of Open Access Journals (Sweden)

    Alberto O. Orden

    2014-06-01

    Full Text Available The principal objective of this investigation was to analyze the association between diffuse idiopathic skeletal hyperostosis (DISH and the presence of aortic valve sclerosis (AVS. For this study we used results from 1000 consecutive outpatients (473 males, older than 50 years of age (average 67.6 years, that had been examined with Doppler echocardiogram and anterior and lateral chest radiographs. Overall, 195 patients (19.5% were diagnosed with DISH and 283 (28.3% with AVS. DISH was more prevalent than AVS in males (66.7% vs. 42.6%, p< 0.0001 and in older patients (73.6 ± 9 years vs. 66.1 ± 9 years, p < 0.0001. Furthermore, 55.4% of patients with dorsal DISH presented aortic sclerosis calcification vs. 21.7% of patients free of DISH (OR = 4.47; 95% CI = 3.22-6.21. The adjusted odds ratio (OR was calculated by sex and age resulting in 3.04 (95% CI = 2.12-4.36; p < .0001. A statistically significant association was found between DISH and AVS in accordance to age and sex. The biological plausibility of this association is based on similar risk factors, pathogenic mechanisms and vascular complications.

  7. Correlation between pretreatment or follow-up CT findings and therapeutic effect of autologous peripheral blood stem cell transplantation for interstitial pneumonia associated with systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Yabuuchi, Hidetake, E-mail: yabuuchi@shs.kyushu-u.ac.jp [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsuo, Yoshio [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsukamoto, Hiroshi [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sunami, Shunya; Kamitani, Takeshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sakai, Shuji [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hatakenaka, Masamitsu [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Nagafuji, Koji; Horiuchi, Takahiko; Harada, Mine; Akashi, Koichi [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2011-08-15

    Purpose: To evaluate what is useful among various parameters including CT findings, laboratory parameters (%VC, %DLco, KL-6), patients related data (age, sex, duration of disease) to discriminate between responder and non-responder in patients who received autologous peripheral blood stem cell transplantation (auto-PBSCT) for interstitial pneumonia (IP) with systemic sclerosis (SSc). Method: Auto-PBSCT and follow-up of at least one year by chest CT, serum KL-6, %VC, and %DLco were performed in 15 patients for IP with SSc. Analyzed CT findings included extent of ground-glass opacity (GGO), intralobular reticular opacity, number of segments that showed traction bronchiectasis, and presence of honeycombing. We regarded the therapeutic response of patients as responders when TLC or VC increase over 10% or DLco increase more than 15%, otherwise we have classified as non-responder. We applied univariate and multivariate analyses to find the significant indicators to discriminate responders from non-responders. P < 0.05 was considered statistically significant. Results: Univariate and multivariate analyses showed that the significant parameter to discriminate responders from non-responders were pretreatment KL-6, presence of honeycombing, extent of GGO, and early change in extent of GGO. Among them, extent of GGO and early change in extent of GGO were the strongest discriminators between responders and non-responders (P = 0.001, 0.001, respectively). Conclusion: Several CT findings and pretreatment KL-6 may be useful to discriminate between responder and non-responder in patients who received auto-PBSCT for IP with SSc.

  8. Optical Elastography of Systemic Sclerosis Skin

    Science.gov (United States)

    2017-09-01

    ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of Houston, 4800 Calhoun Road, Houston, TX The University of Texas Health Science ...o What was the impact on society beyond science and technology? Nothing to Report. 5.CHANGES/PROBLEMS: o Changes in approach and reasons for...Sclerosis Patient-Derived Data Role: PI Time Commitment: 0.24 calendar mos Supporting Agency: Momenta Pharmaceuticals , Inc Name and Address of the

  9. High resolution computed tomography in patients with various forms of systemic sclerosis

    International Nuclear Information System (INIS)

    Lewszuk, A.; Rozycki, J.; Tarasow, E.; Kowal-Bielecka, O.

    2008-01-01

    Pulmonary lesions are, besides renal and cardiac complications, one of the main causes of mortality among patients with systemic sclerosis (scleroderma). Pathologic changes in the respiratory system take the form of interstitial fibrosis clinically manifested by progressive exertion dyspnea and abnormalities of respiratory restriction type in functional tests. The aim of the study was systematization of pulmonary lesion symptomatology in conventional chest radiography and high resolution computed tomography (HRCT) in patients with various forms of scleroderma, as well as determination of the frequency and localization of the particular lesion types. The study was carried out in a group of 49 patients with systemic sclerosis (47 women and 2 men), who underwent conventional radiography and high resolution computed tomography of the chest. In patients with systemic sclerosis, HRCT revealed most frequently interstitial changes of ground glass type, as well as linear and reticular opacities, whereas bronchiectasis and honeycombing type lesions were less frequent. Pulmonary lesions were seen with increasing frequency towards the lung base and were localized mainly in the posterior, inferior and peripheral parts of the lungs. Comparison of the patients with limited and diffuse scleroderma demonstrated that the diffuse form is associated with more frequent involvement of the respiratory system and more advanced pulmonary lesions. The observed characteristics of pulmonary lesions show similarity between interstitial lung disease in the course of systemic sclerosis and nonspecific interstitial pneumonia (NSIP), which supports classification of interstitial lung disease associated with scleroderma as belonging to that group of interstitial inflammations. (author)

  10. Temporal lobe sclerosis associated with hippocampal sclerosis in temporal lobe epilepsy: neuropathological features.

    Science.gov (United States)

    Thom, Maria; Eriksson, Sofia; Martinian, Lillian; Caboclo, Luis O; McEvoy, Andrew W; Duncan, John S; Sisodiya, Sanjay M

    2009-08-01

    Widespread changes involving neocortical and mesial temporal lobe structures can be present in patients with temporal lobe epilepsy and hippocampal sclerosis. The incidence, pathology, and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 of 272 surgically treated cases of hippocampal sclerosis. Temporal lobe sclerosis was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, that is, abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases, there was a gradient of TLS with more severe involvement toward the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared with 36% without TLS; no other clinical differences between TLS and non-TLS cases were identified. Temporal lobe sclerosis was not evident preoperatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2-year follow-up. In conclusion, approximately 11% of surgically treated hippocampal sclerosis is accompanied by TLS. Temporal lobe sclerosis is likely an acquired process with accompanying reorganizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity.

  11. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    NARCIS (Netherlands)

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, Jose Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Terue, Maria; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; Lopez-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Angel Gonzalez-Gay, Miguel; Zhernakova, Alexandra; Padyukov, Leonid; Aarcon-Riquelme, Marta; Wijmenga, Cisca; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jorg H. W.; Voskuy, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airo, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic

  12. Clinical risk assessment of organ manifestations in systemic sclerosis

    DEFF Research Database (Denmark)

    Walker, U A; Tyndall, A; Czirják, L

    2007-01-01

    Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its tre...... treatment, the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004....

  13. Treatment outcome in early diffuse cutaneous systemic sclerosis

    DEFF Research Database (Denmark)

    Herrick, Ariane L; Pan, Xiaoyan; Peytrignet, Sébastien

    2017-01-01

    OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study...

  14. Association of copeptin and cortisol in newly diagnosed multiple sclerosis patients.

    Science.gov (United States)

    Baranowska-Bik, Agnieszka; Kochanowski, Jan; Uchman, Dorota; Litwiniuk, Anna; Kalisz, Malgorzata; Martynska, Lidia; Wolinska-Witort, Ewa; Baranowska, Boguslawa; Bik, Wojciech

    2015-05-15

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Obesity may increase the risk of developing MS. The aim of this study was to evaluate copeptin and cortisol plasma levels in newly diagnosed untreated MS patients and to determine whether copeptin and cortisol are related to the patients' clinical statuses. We report that copeptin and cortisol were higher in overweight/obese MS patients. Positive correlations were observed between the two parameters. We conclude that alterations of copeptin and cortisol levels in multiple sclerosis patients may be related to adiposity. An increase in cortisol may also be associated with copeptin secretion. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Cannabinoids in the management of spasticity associated with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Anna Maria Malfitano

    2008-08-01

    Full Text Available Anna Maria Malfitano, Maria Chiara Proto, Maurizio BifulcoDipartimento di Scienze Farmaceutiche, Università degli Studi di SalernoAbstract: The endocannabinoid system and cannabinoid-based treatments have been involved in a wide number of diseases. In particular, several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis (MS. In this study we highlight the main findings reported in literature about the relevance of cannabinoid drugs in the management and treatment of MS. An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of MS, including spasticity and pain. In this report we focus on the effects of cannabinoids in the relief of spasticity describing the main findings in vivo, in the mouse experimental allergic encephalomyelitis model of MS. We report on the current treatments used to control MS symptoms and the most recent clinical studies based on cannabinoid treatments, although long-term studies are required to establish whether cannabinoids may have a role beyond symptom amelioration in MS.Keywords: cannabinoids, multiple sclerosis, spasticity

  16. Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies

    NARCIS (Netherlands)

    López-Isac, Elena; Martín, Jose Ezequiel; Assassi, Shervin; Simeón, Carmen P.; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J.; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M.; González-Gay, Miguel A.; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg H W; Riekemasten, Gabriella; van der Helm-van Mil, Annette H.; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E.; Vonk, Madelon C.; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby P C; Denton, Christopher P.; Fonseca, Carmen; Radstake, Timothy R D J; Worthington, Jane; Mayes, Maureen D.; Martín, Javier; Ríos, Raquel; Callejas, Jose Luis; Hitos, José Antonio Vargas; Portales, Rosa García; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; García-Hernández, Francisco José; Castillo, Ma Jesús; Ángeles Aguirre, Ma; Gómez-Gracia, Inmaculada; Rodríguez-Rodríguez, Luis; Peña, Paloma García de la; Vicente, Esther; Andreu, José Luis; de Castro, Mónica Fernández; López-Longo, Francisco Javier; Martínez, Lina; Fonollosa, Vicente; Guillén, Alfredo; Castellví, Iván; Espinosa, Gerard; Tolosa, Carlos; Pros, Anna; Carballeira, Mónica Rodríguez; Narváez, Francisco Javier; Rivas, Manel Rubio; Ortiz-Santamaría, Vera; Madroñero, Ana Belén; Díaz, Bernardino; Trapiella, Luis; Sousa, Adrián; Egurbide, María Victoria; Mateo, Patricia Fanlo; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma; Román-Ivorra, José Andrés; Grau, Elena; Alegre-Sancho, Juan José; Blanco García, Francisco J.; Oreiro, Natividad

    2016-01-01

    Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new

  17. Fatigue Perceived by Multiple Sclerosis Patients Is Associated With Muscle Fatigue

    NARCIS (Netherlands)

    Steens, Anneke; de Vries, Astrid; Hemmen, Jolien; Heersema, Thea; Heerings, Marco; Maurits, Natasha; Zijdewind, Inge

    Background. Fatigue is a debilitating symptom in multiple sclerosis (MS). Previous studies showed no association between fatigue as perceived by the patient and physiological measures of fatigability. Objective. The authors investigated associations between perceived fatigue and measures of

  18. [The treatment of skin ulcers in patients with systemic sclerosis].

    Science.gov (United States)

    Fiori, G; Amanzi, L; Moggi Pignone, A; Braschi, F; Matucci-Cerinic, M

    2004-01-01

    Systemic Sclerosis (Ssc) is a complex disease of the connective tissue, characterized by progressive thickening and fibrosis of the skin and the internal organs and by diffused damage of the microvascular system. The fibrosis ones of the skin associated to the characteristic vascular alterations lead to the genesis of ulcers, more or less extended, often multiple, peripheral localization, chronic course, painful, able to influence patient's quality of life. Indeed, immunity reactivity, the thinning and the loss of elasticity of the skin, the peripheral neurological damage and the eventual drug assumption that can reduce regenerative/reparative abilities, can easily make an ulcer chronic and become infected complicating still more the patient disease, rendering more difficult the cure often, ulcer evolves to gangrene, and in some cases, in amputation too. For all these reasons, we have begun to study ulcers therapy (local and systemic), considering this activity it leave integrating of the charitable distance of the sclerodermic patient, putting to point on strategy both diagnostic and therapeutic, but above all with the primary scope, if possible, is to prevent ulcers, in contrary case, to alleviate the pain and to render the quality of the life of the patient better.

  19. The treatment of skin ulcers in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    M. Matucci- Cerinic

    2011-09-01

    Full Text Available Systemic Sclerosis (Ssc is a complex disease of the connective tissue, characterized by progressive thickening and fibrosis of the skin and the internal organs and by diffused damage of the microvascular system. The fibrosis ones of the skin associated to the characteristic vascular alterations lead to the genesis of ulcers, more or less extended, often multiple, peripheral localization, chronic course, painful, able to influence patient’s quality of life. Indeed, immunity reactivity, the thinning and the loss of elasticity of the skin, the peripheral neurological damage and the eventual drug assumption that can reduce regenerative/reparative abilities, can easy chronicizzate an ulcer and become infected complicating still more the patient disease, rendering more difficult the cure often, ulcer evolves to gangrene, and in some cases, in amputation too. For all these reasons, we have begun to study ulcers therapy (local and systemic, considering this activity it leave integrating of the charitable distance of the sclerodermico patient, putting to point on strategy both diagnostic and therapeutic, but above all with the primary scope, if possible, is to prevent ulcers, in contrary case, to alleviate the pain and to render the quality of the life of the patient better.

  20. Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

    Science.gov (United States)

    Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

    2010-11-01

    Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

  1. Association between macronutrient intake and amyotrophic lateral sclerosis prognosis.

    Science.gov (United States)

    Kim, Boeun; Jin, Youri; Kim, Seung Hyun; Park, Yongsoon

    2018-04-24

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and the nutritional state of ALS patients is associated with survival. The purpose of the present study was to investigate whether macronutrient intake at early stage of the disease was positively associated with survival and duration from symptom onset to death, tracheostomy, or non-invasive ventilation (NIV) in ALS. ALS patients diagnosed according to EI Escorial criteria were recruited from 2011 to 2016 and followed up until 2017, when they reached the endpoint of death, tracheostomy, or NIV use. Dietary intake was estimated based on a 24-hour recall conducted less than 2 years from symptom onset, and the survival time was defined as the duration from symptom onset to the endpoint. ALS patients were categorized as short-term group (n=79) and long-term group (n=69) according to the mean survival time (33.03±14.01 months). Short-term survival was negatively associated with fat, protein, and meat intake, and positively associated with carbohydrate intake after adjustment for confounders. In addition, the survival time was positively associated with fat, protein, and meat intake but was not associated with carbohydrate intake. The present study suggested that higher intake of fat and protein, particularly from meat at early stage of the disease, could prolong the survival of ALS patients. However, further clinical trials are necessary to confirm the beneficial effects of higher fat and protein intake on mortality in ALS patients.

  2. Systemic Sclerosis and the Gastrointestinal Tract-Clinical Approach.

    Science.gov (United States)

    Braun-Moscovici, Yolanda; Brun, Rita; Braun, Marius

    2016-10-31

    Systemic sclerosis (SSc) is a multisystem disease characterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs, immune system activation, and autoimmunity. The gastrointestinal tract is involved in nearly all patients and is a source of significant morbidity and even mortality. The aim of this review is to summarize the pathogenesis and to provide a clinical approach to these patients.

  3. Tuberous sclerosis

    Directory of Open Access Journals (Sweden)

    Krishnan S

    1996-01-01

    Full Text Available Although tuberous sclerosis has been described with a diagnostic triad, it is not present consistently in all cases. Variety of skin manifestations were reported in tuberous sclerosis. This studay was undertaken to assess the frequency of various skin changes in tuberous sclerosis. Ten consecutive cases of tuberous sclerosis were studied. Angiofibroma was the commonest cutaneous manifestation. Atypical fibroxanthoma, dermatofibroma and neurofibroma were also noticed as interesting associations.

  4. The role of platelets in the pathogenesis of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Giuseppe A. eRamirez

    2012-06-01

    Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

  5. Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Tracy M. Frech

    2016-01-01

    Full Text Available The gastrointestinal tract (GIT is the most common extracutaneous organ system damaged in systemic sclerosis (SSc and is the presenting feature in 10% of patients. The esophagus as the portion of the GIT is the most commonly affected and there is an association of gastroesophageal reflux (GER with SSc interstitial lung disease (ILD. Thus, an aggressive treatment for GER is recommended in all SSc patients with ILD; however, it is recognized that a long-term benefit to this treatment is needed to understand its impact. In this case report we discuss the presence of eosinophilic esophagitis (EoE in two SSc patients and discuss the role for early EGD in SSc patients with moderate-severe GER symptoms for tissue study. Assessment of esophageal biopsy specimens for the presence of eosinophils and possibly ANA can help elucidate disease pathogenesis and direct therapy, as the presence of EoE in SSc has important management considerations, particularly with regards to dietary modification strategies.

  6. Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Maddern, G.J.; Horowitz, M.; Jamieson, G.G.; Chatterton, B.E.; Collins, P.J.; Roberts-Thomson, P.

    1984-01-01

    Gastric and esophageal emptying were assessed using scintigraphic techniques in 12 patients with progressive systemic sclerosis and 22 normal volunteers. Esophageal emptying was significantly delayed in the patient group, with 7 of the 12 patients beyond the normal range. Gastric emptying was slower in patients than in controls, with 9 patients being outside the normal range for solid emptying and 7 patients outside the normal range for liquid emptying. Findings from gastric and esophageal emptying tests generally correlated well with symptoms of dysphagia and gastroesophageal reflux. However, 2 patients with normal emptying studies had symptomatic heartburn, and 2 patients with delay of both solid and liquid gastric emptying gave no history of gastroesophageal reflux. Delayed gastric emptying may be an important factor in the development of upper gastrointestinal symptoms in patients with progressive systemic sclerosis

  7. Systemic Sclerosis Sine Scleroderma in Mexican Patients. Case Reports.

    Science.gov (United States)

    Vera-Lastra, Olga; Sauceda-Casas, Christian Alexis; Domínguez, María Del Pilar Cruz; Alvarez, Sergio Alberto Mendoza; Sepulceda-Delgado, Jesús

    2017-01-03

    Systemic sclerosis sine scleroderma (ssSSc) is a form of systemic sclerosis that is characterized by Raynaud's phenomenon (RP), visceral involvement without thickening of skin and anticentromere antibodies (ACA). We studied 10 ssSsc patients with a prevalence of 2%. The clinical signs were: RP 9/10, esophageal manifestations 8/10, pulmonary arterial hypertension 4/10, interstitial lung disease 4/10, cardiac signs 3/10 and ACA 8/10. In patients with RP, esophageal dysmotility, interstitial lung disease and pulmonary arterial hypertension should be tested for ACA in order to establish a prompt diagnosis and treatment of ssSSc. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  8. Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Maddern, G.J.; Horowitz, M.; Jamieson, G.G.; Chatterton, B.E.; Collins, P.J.; Roberts-Thomson, P.

    1984-10-01

    Gastric and esophageal emptying were assessed using scintigraphic techniques in 12 patients with progressive systemic sclerosis and 22 normal volunteers. Esophageal emptying was significantly delayed in the patient group, with 7 of the 12 patients beyond the normal range. Gastric emptying was slower in patients than in controls, with 9 patients being outside the normal range for solid emptying and 7 patients outside the normal range for liquid emptying. Findings from gastric and esophageal emptying tests generally correlated well with symptoms of dysphagia and gastroesophageal reflux. However, 2 patients with normal emptying studies had symptomatic heartburn, and 2 patients with delay of both solid and liquid gastric emptying gave no history of gastroesophageal reflux. Delayed gastric emptying may be an important factor in the development of upper gastrointestinal symptoms in patients with progressive systemic sclerosis.

  9. The Role of PPAR Gamma in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Andréa Tavares Dantas

    2015-01-01

    Full Text Available Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc, an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.

  10. Lymphatic microangiopathy of the skin in systemic sclerosis.

    Science.gov (United States)

    Leu, A J; Gretener, S B; Enderlin, S; Brühlmann, P; Michel, B A; Kowal-Bielecka, O; Hoffmann, U; Franzeck, U K

    1999-03-01

    The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

  11. Environmental Mycobiome Modifiers of Inflammation and Fibrosis in Systemic Sclerosis

    Science.gov (United States)

    2016-09-01

    shown that PBMCs and macrophages from SSc patients (monocytes isolated from peripheral blood of SSc patients that are differentiated in autologous...systemic sclerosis, pulmonary fibrosis and pulmonary arterial hypertension ” Scleroderma Research Foundation Annual Workshop, San Francisco, CA 2/16...Cruz), and patient sera for 1 h at room temperature. Secondary antibodies (anti-goat-Cy3, anti-mouse-Cy2, and anti-human-Cy5) were purchased from

  12. Small intestinal bacterial overgrowth in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Saara Rawn

    2017-01-01

    Full Text Available Small intestinal bacterial overgrowth (SIBO is common in patients with systemic sclerosis (SSc yet often goes underrecognized in clinical practice. In patients with SSc, untreated SIBO may result in marked morbidity and possible mortality. The pathogenesis of SIBO is multifactorial and relates to immune dysregulation, vasculopathy, and dysmotility. This article reviews various diagnostic approaches and therapeutic options for SIBO. Treatment modalities mainly include prokinetics, probiotics, and antibiotics.

  13. 131I albumin of patients carrying progressive systemic sclerosis study

    International Nuclear Information System (INIS)

    Cossermelli, W.; Carvalho, N.; Papaleo Netto, M.

    1974-01-01

    131 I albumin metabolic changes were studied in 14 female patients with progressive systemic sclerosis. A statistical study of the gathered data disclosed increased distribution and turnover half-life and diminished turnover rate of radioactive substance. Since T/2 of turnover and turnover rate are the result produced by the albumin synthesis and degradation, they are probably lowered during active disease causing hypoalbuminemia. The aminoacids also are probably absorbed by other protein like the gammaglobuline synthesis [pt

  14. Circulating angiostatin serum level in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zofia Gerlicz-Kowalczuk

    2017-12-01

    Full Text Available Introduction : Systemic sclerosis (SSc is achronic connective tissue disease characterized by microangiopathy with inadequate angiogenesis. Angiostatin (AS is a potent antiangiogenic factor specifically inhibiting proliferation and inducing apoptosis of vascular endothelial cells. Aim : To evaluate the level of angiostatin in the serum of patients with SSc. Material and methods : Serum levels of AS were measured in 20 SSc patients and 12 healthy controls. Results : A statistically significant difference in the serum levels of AS in SSc patients was observed compared to the control group (636.51 vs. 869.20 ng/ml; p = 0.012. Significant correlations between limited and disseminated SSc (lSSc/dSSc were not found, however, a difference between lSSc and the control group was demonstrated (620.00 vs. 869.20 ng/ml; p = 0.011. The serum level of AS was not associated positively with organ changes caused by SSc. However, a statistically significant lower serum level of AS was observed in patients with SSc and no esophageal (p = 0.008 or pulmonary changes (p = 0.007 compared to the control group. Conclusions : Our results reveal significant differences in AS level in SSc patients compared to the healthy controls, and suggest that a low level of AS may occur as a result of impaired angiogenesis.

  15. Radiological evaluation of swallowing and clinical patterns of systemic sclerosis

    International Nuclear Information System (INIS)

    Montesi, A.; Pesaresi, A.; Cavalli, M.L.; Serri, L.; Salmistraro, D.; Candela, M.; Gabrielli, A.

    1990-01-01

    Fifty-one patients with systemic sclerosis (scleroderma) were studied by means of videofluoroscopy in order to evaluate the abnormalities in the oral-pharyngeal and esophageal phases of deglutition and to correlate the radiological patterns with the clinical features of the disease. Thirteen patients (25.5%) exhibited swallowing disorders such as oral leakage, retention, penetration, mild or moderate aspiration and abnormal upper esophageal sphincter behavior. These dysfunctions were more evident in patients with esophageal motility abnormalities. A normal radiological pattern in the esophagus was not associated with swallowing alterations. Remarkably, patients with oral-pharyngeal disorders had a higher incidence of lung diseases. Forty-five patients (88%) exhibited disorders of the esophageal phase of deglutition, such as mild or severe motility abnormalities or hiatal hernia, gastro-esophageal reflux, reflux esophagitis, and stricture. Radiological findings in the esophagus can be abnormal in the early stages of the disease. On the other hand, the radiological pattern of esophageal motility can be occasionally negative in advanced or extensive disease. This indicates a discrepancy between clinical symptoms and radiological picture of the esophagus. The radiological examination of the oral-pharyngeal and esophageal phases of deglutition is important in patients with scleroderma in order to evaluate visceral involvement, motility disorders, and risk of aspiration. Such radiological information can be useful in preventing esophagitis and pulmonary complications

  16. Solvent oriented hobbies and the risk of systemic sclerosis.

    Science.gov (United States)

    Nietert, P J; Sutherland, S E; Silver, R M; Pandey, J P; Dosemeci, M

    1999-11-01

    To examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Scl70 antibody. Patients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Scl70. Solvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Scl70 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9). While patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Scl70 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc.

  17. Relationship between disease characteristics and orofacial manifestations in systemic sclerosis: Canadian Systemic Sclerosis Oral Health Study III.

    Science.gov (United States)

    Baron, Murray; Hudson, Marie; Tatibouet, Solène; Steele, Russell; Lo, Ernest; Gravel, Sabrina; Gyger, Geneviève; El Sayegh, Tarek; Pope, Janet; Fontaine, Audrey; Masetto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira, Getulio; Robinson, David; Fritzler, Marvin; Gornitsky, Mervyn

    2015-05-01

    Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities. Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined. One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren's syndrome-related autoantibodies (β = -43.32; 95% confidence interval [95% CI] -80.89, -5.75), but not with disease severity (β = -2.51; 95% CI -8.75, 3.73). Decreased interincisal distance was related to disease severity (β = -1.02; 95% CI -1.63, -0.42) and the modified Rodnan skin thickness score (β = -0.38; 95% CI -0.53, -0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease. In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren's syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear. © 2015, American College of Rheumatology.

  18. Gastric antral vascular ectasia--a cause of refractory anaemia in systemic sclerosis.

    LENUS (Irish Health Repository)

    Busteed, S

    2012-02-03

    Recurrent gastrointestinal haemorrhage is an uncommon manifestation of systemic sclerosis. We report a case of gastrointestinal bleeding due to gastric antral vascular ectasia (GAVE) in a patient with systemic sclerosis. Failure to recognise the condition as a cause of gastrointestinal bleeding may delay the instigation of appropriate treatment. GAVE should be considered in the differential diagnosis of anaemia in patients with autoimmune conditions such as systemic sclerosis and primary biliary cirrhosis.

  19. Radiographic changes of the distal phalangeal tuft of the hands in subjects with systemic sclerosis. Systematic review.

    Science.gov (United States)

    Izquierdo, Yojhan Edilberto; Calvo Páramo, Enrique; Castañeda, Luisa María; Gómez, Sandra Viviana; Zambrano, Fernán Santiago

    To determine abnormal plain radiograph findings of the distal phalanx tuft of the hand (DPTH) associated with systemic sclerosis in adults. A systematic review was developed following the parameters of the PRISMA guidelines in databases: MEDLINE, EMBASE, BIREME, Scielo, Google Scholar and others including as primary outcomes alterations of DPTH (erosions, resorption, sclerosis and proliferation) detected by simple radiography in subjects with systemic sclerosis. The prevalence of radiographic findings was synthesized using the fixed effects model. The statistical associations were expressed in terms of relative risk or odds ratio with their respective confidence intervals and p values. Twenty-two observational studies were included; the prevalence of DPTH resorption was 28.3% (95% CI: 0.256-0.312; p < .001); I 2 =80.4%, the prevalence of calcinosis was 15.6% (95% CI: 0.113-0.210; p < .001); I 2 =0%. No study reported proliferation or erosions and only one study described sclerosis of DPTH in 5 individuals. Resorption and calcinosis of DPTH are the characteristic radiographic findings in patients with systemic sclerosis. However, new studies with greater methodological strength are needed to establish associations between these phenomena and their presence in other connective tissue diseases. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  20. HLA DRB5*01 Association Survey with Multiple Sclerosis in Khuzestan Province of Iran

    Directory of Open Access Journals (Sweden)

    Tahereh Latifi Pakdehi

    2017-08-01

    Full Text Available Background Multiple sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system (CNS. Although the cause of MS is currently unknown, both genetic and environmental factors have been shown to contribute to the pathogenesis of MS. The human leukocyte antigen (HLA class II alleles DRB1*1501, DRB5*0101, DQA1*0102, DQB1*0602 may have an important genetic effect. However, this is controversial in different population studies. Objectives The aim of this study was to investigate the correlation of HLA DRB5*01 with MS in Khuzestan province. Methods The present case-control study focused on HLA DRB5*01 association in 202 MS patients from Khuzestan. Seventy four point two five percent (74.25% of patients classified as relapsing-remitting and other patients were as primary-progressive, secondary progressive and progressive-relapsing MS. One hundred eighty seven persons that have no any inflammatory diseases investigated as control group. Polymerase chain reaction amplification method was performed to determine the type of HLA with sequence-specific primers (PCR-SSP. The frequencies of the mentioned allele were compared between the patients and control group using SPSS 21 statistical software and the chi square test. Results Twenty- seven point seven two percent (27.72% of patients and 21.39% from the control group were positive with this type of HLA. Conclusions This is the first study that investigate HLA DRB5*01 association with multiple sclerosis patients in Khuzestan. We found that there is no association between HLA DRB5*01 with multiple sclerosis in Khuzestan province (P = 0.148.

  1. Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

    2017-07-01

    The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

  2. Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Marija Vavlukis

    2015-11-01

    CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis.

  3. Correlation between serum E-selectin levels and panoramic nailfold capillaroscopy in systemic sclerosis.

    Science.gov (United States)

    Valim, V; Assis, L S S; Simões, M F J; Trevisani, V F M; Pucinelli, M L C; Andrade, L E C

    2004-09-01

    E-selectin is expressed by the activated endothelium and its plasma levels are increased in patients with systemic sclerosis. Eighteen patients fulfilling the American Rheumatism Association criteria for systemic sclerosis, 15 females and 3 males, 42-70 years old, 9 with diffuse and 9 with limited forms, were sequentially recruited for this study. Serum E-selectin levels were determined by commercially available ELISA and their association with nailfold capillaroscopic abnormalities was investigated. Nailfold capillaries were analyzed by 16X magnification wide-field capillaroscopy. Two parameters on capillaroscopy were used to correlate to serum E-selectin: deletion and ectasia. Data were analyzed statistically by the Student t-test and Spearman correlation. Two-tailed P values below 0.05 were considered significant. E-selectin range was 38 to 200 ng/ml (80 +/- 39.94). There was a correlation between serum E-selectin levels and the deletion capillaroscopic score (r = 0.50, P capillaroscopy. The stronger correlation of deletion score in capillaroscopy in early disease suggests that serum E-selectin levels might be a useful biochemical marker of disease activity in systemic sclerosis.

  4. Cutaneous Adverse Events Associated with Interferon-β Treatment of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Annette Kolb-Mäurer

    2015-07-01

    Full Text Available Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

  5. Brain MRI screening showing evidences of early central nervous system involvement in patients with systemic sclerosis.

    Science.gov (United States)

    Mohammed, Reem Hamdy A; Sabry, Yousriah Y; Nasef, Amr A

    2011-05-01

    Systemic sclerosis is a multisystem autoimmune collagen disease where structural and functional abnormalities of small blood vessels prevail. Transient ischemic attacks, ischemic stroke, and hemorrhage have been reported as primary consequence of vascular central nervous system affection in systemic sclerosis. Magnetic resonance imaging is considered to be the most sensitive diagnostic technique for detecting symptomatic and asymptomatic lesions in the brain in cases of multifocal diseases. The objective of this study is to detect subclinical as well as clinically manifest cerebral vasculopathy in patients with systemic sclerosis using magnetic resonance imaging. As much as 30 female patients with systemic sclerosis aged 27-61 years old, with disease duration of 1-9 years and with no history of other systemic disease or cerebrovascular accidents, were enrolled. Age-matched female control group of 30 clinically normal subjects, underwent brain magnetic resonance examination. Central nervous system (CNS) involvement in the form of white matter hyperintense foci of variable sizes were found in significantly abundant forms in systemic sclerosis patients on magnetic resonance evaluation than in age-related control group, signifying a form of CNS vasculopathy. Such foci showed significant correlation to clinical features of organic CNS lesion including headaches, fainting attacks and organic depression as well as to the severity of peripheral vascular disease with insignificant correlation with disease duration. In conclusion, subclinical as well as clinically manifest CNS ischemic vasculopathy is not uncommon in systemic sclerosis patients and magnetic resonance imaging is considered a sensitive noninvasive screening tool for early detection of CNS involvement in patients with systemic sclerosis.

  6. Gastric involvement in systemic sclerosis: a prospective study.

    Science.gov (United States)

    Marie, I; Levesque, H; Ducrotté, P; Denis, P; Hellot, M F; Benichou, J; Cailleux, N; Courtois, H

    2001-01-01

    This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances. Fasting and postprandial gastric electrical activity was studied in 22 consecutive patients with SSc (17 with and 5 without clinical gastric manifestations) and 22 age- and sex-matched healthy subjects. Gastric emptying of radiopaque pellets and gastroscopy were also performed in SSc patients. The prevalence of EGG disturbances was as high as 81.82% in SSc patients. SSc patients exhibited, compared with controls, higher median percentage of dominant frequency in bradygastria during the fasting period and lower median values for postprandial electrical power and postprandial to fasting ratio for electrical power. Gastric emptying of radiopaque pellets was delayed in 11 SSc patients, and gastroscopy demonstrated "watermelon stomach" in 3 SSc patients. No correlation was found between the severity of gastric impairment and clinical presentation, SSc duration and subsets, and esophageal manometric impairment. Our study underlines the high frequency of gastric dysfunction in SSc patients. It suggests the usefulness of EGG in SSc in noninvasively detecting disorders of gastric electrical activity at an early stage and symptomatic patients with gastroparesis (because there was a correlation between values of postprandial to fasting ratio for electrical power of watermelon stomach diagnosis should be excluded in SSc patients presenting with gastrointestinal hemorrhage or with anemia related to iron deficiency.

  7. Central Hemodynamics and Arterial Stiffness in Systemic Sclerosis.

    Science.gov (United States)

    Bartoloni, Elena; Pucci, Giacomo; Cannarile, Francesca; Battista, Francesca; Alunno, Alessia; Giuliani, Marco; Cafaro, Giacomo; Gerli, Roberto; Schillaci, Giuseppe

    2016-12-01

    Although microvascular disease is a hallmark of systemic sclerosis (SSc), a higher prevalence of macrovascular disease and a poorer related prognosis have been reported in SSc than in the general population. The simultaneous assessment of prognostically relevant functional properties of larger and smaller arteries, and their effects on central hemodynamics, has never been performed in SSc using the state-of-the-art techniques. Thirty-four women with SSc (aged 61±15 years, disease duration 17±12 years, and blood pressure 123/70±18/11 mm Hg) and 34 healthy women individually matched by age and mean arterial pressure underwent the determination of carotid-femoral (aortic) and carotid-radial (upper limb) pulse wave velocity (a direct measure of arterial stiffness), aortic augmentation (a measure of the contribution of reflected wave to central pulse pressure), and aortobrachial pulse pressure amplification (brachial/aortic pulse pressure) through applanation tonometry (SphygmoCor). Patients and controls did not differ by carotid-femoral or carotid-radial pulse wave velocity. Aortic augmentation index corrected for a heart rate of 75 bpm (AIx@75) was higher in women with SSc (30.9±16% versus 22.2±12%; P=0.012). Patients also had a lower aortobrachial amplification of pulse pressure (1.22±0.18 versus 1.33±0.25; P=0.041). SSc was an independent predictor of AIx@75 (direct) and pulse pressure amplification (inverse). Among patients, age, mean arterial pressure, and C-reactive protein independently predicted carotid-femoral pulse wave velocity. Age and mean arterial pressure were the only predictors of AIx@75. Women with SSc have increased aortic augmentation and decreased pulse pressure amplification (both measures of the contribution of reflected wave to central waveform) but no changes in aortic or upper limb arterial stiffness. Microvascular involvement occurs earlier than large artery stiffening in SSc. © 2016 American Heart Association, Inc.

  8. Evaluation of the extent of ground-glass opacity on high-resolution CT in patients with interstitial pneumonia associated with systemic sclerosis: Comparison between quantitative and qualitative analysis

    International Nuclear Information System (INIS)

    Yabuuchi, H.; Matsuo, Y.; Tsukamoto, H.; Horiuchi, T.; Sunami, S.; Kamitani, T.; Jinnouchi, M.; Nagao, M.; Akashi, K.; Honda, H.

    2014-01-01

    Aim: To verify whether quantitative analysis of the extent of ground-glass opacity (GGO) on high-resolution computed tomography (HRCT) could show a stronger correlation with the therapeutic response of interstitial pneumonia (IP) associated with systemic sclerosis (SSc) compared with qualitative analysis. Materials and methods: Seventeen patients with IP associated with SSc received autologous peripheral blood stem cell transplantation (auto-PBSCT) and were followed up using HRCT and pulmonary function tests. Two thoracic radiologists assessed the extent of GGO on HRCT using a workstation. Therapeutic effect was assessed using the change of vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLco) before and 12 months after PBSCT. Interobserver agreement was assessed using Spearman's rank correlation coefficient and the Bland–Altman method. Correlation with the therapeutic response between quantitative and qualitative analysis was assessed with Pearson's correlation coefficients. Results: Spearman's rank correlation coefficient showed good agreement, but Bland–Altman plots showed that proportional error could be suspected. Quantitative analysis showed stronger correlation than the qualitative analysis based on the relationships between the change in extent of GGO and VC, and change in extent of GGO and DLco. Conclusion: Quantitative analysis of the change in extent of GGO showed stronger correlation with the therapeutic response of IP with SSc after auto-PBSCT than with the qualitative analysis. - Highlights: • Quantitative analysis of GGO in IP showed strong correlation with therapeutic effect. • Qualitative analysis might be limited by interobserver variance. • Other parameters including reticular opacities remain in a future investigation

  9. The role of information system in multiple sclerosis management.

    Science.gov (United States)

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-12-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management.

  10. Surgical management of gastroesophageal reflux disease in patients with systemic sclerosis.

    Science.gov (United States)

    Yan, Jingliang; Strong, Andrew T; Sharma, Gautam; Gabbard, Scott; Thota, Prashanti; Rodriguez, John; Kroh, Matthew

    2018-02-12

    Systemic sclerosis (scleroderma) is frequently associated with both gastroesophageal reflux disease (GERD) and simultaneous esophageal dysmotility. Anti-reflux procedures in this patient population must account for the existing physiology of each patient and likely disease progression. We aim to compare perioperative and intermediate outcomes of fundoplication versus gastric bypass for the treatment of GERD. After IRB approval, patients with systemic sclerosis undergoing fundoplication or gastric bypass for the treatment of GERD from 2004 to 2016 were identified. Demographics, perioperative data, immediate complications, and symptom improvement were retrieved and analyzed. Fourteen patients with systemic sclerosis underwent surgical treatment of GERD during the defined study period. Average body mass index was 26 kg/m 2 . Seven fundoplications (2 Nissens, 4 Toupets, and 1 Dor) and 7 Roux-en-Y gastric bypasses (RYGB) were performed. No 30-day mortality was observed in either group. Median follow-up was 97 months for the fundoplication group (range 28-204 months), and 19 months for the RYGB group (range 1-164 months). Preoperatively, dysphagia, heartburn, and regurgitation were present in 71% (n = 10), 86% (n = 12), and 64% (n = 9) of patients, respectively. Eleven patients had pH study prior to surgical intervention, and 91% of them had abnormal acid exposure. Esophagitis was evident in 85% (n = 11) of patients during preoperative upper endoscopy, and two patients had Barrett's esophagus. Impaired esophageal motility was present in all RYGB patients and 71% of fundoplication patients. Of the patients who had assessment of their GERD symptoms at follow-up, all five patients in the RYGB group and only 3 (50%) patients in the fundoplication group reported symptom improvement or resolution. Laparoscopic RYGB as an anti-reflux procedure is safe and may provide an alternative to fundoplication in the treatment of GERD for systemic sclerosis patients

  11. Radiological changes of the hands of systemic sclerosis

    International Nuclear Information System (INIS)

    Brun, B.; Serup, J.; Hagdrup, H.

    1983-01-01

    Radiological examination of the hands was performed in 41 patients with systemic sclerosis. Pathological changes were found in 39 patients. Eighteen patients had subcutaneous calcifications and 11 had atrophy of the finger pulps. Bone resorption of ungual tufts was found in 11 patients. Juxta-articular osteoporosis was seen in 9 patients and periarticular bone erosions in 8 patients indicating erosive arthropathy. Osteoarthritis and generalized osteoporosis were seen in 10 and 7 patients, respectively. Radiological examination of the hands is recommended during treatment. (Authors)

  12. 67Gallium lung scans in progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Baron, M.; Feiglin, D.; Hyland, R.; Urowitz, M.B.; Shiff, B.

    1983-01-01

    67 Gallium lung scans were performed in 19 patients with progressive systemic sclerosis (scleroderma). Results were expressed quantitatively as the 67 Gallium Uptake Index. The mean total pulmonary 67 Gallium Uptake Index in patients was significantly higher than that in controls (41 versus 25), and 4 patients (21%) fell outside the normal range. There were no clinical or laboratory variables that correlated with the 56 Gallium uptake. Increased pulmonary 67 Gallium uptake in scleroderma may prove useful as an index of pulmonary disease activity

  13. Radiology of the hand in progressive systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Scutellari, P N; Orzincolo, C; Delli Gatti, I. and others

    1986-01-01

    Radiographs and xerographs of the hands of 35 patients with progressive systematic sclerosis (PSS), as defined by the ARA, were reviewed. Patients with ''overlap'' syndromes (i.e., mixed connective tissue disease, systemic lupus erythematosus or rheumatoid arthritis) have been excluded. Soft tissue changes included atrophy (hidebound skin), and dystrophic calcifications, particularly in CREST patients (calcinosis, Raynaud phenomenon, esophageal dysmobility, sclerodactily and telangectasia). The most common bony change is resorption of distal phalanges; diffuse osteoporosis is also frequent; the distal interphalangeal and first carpometacarpal joints involvement appear as a distinctive feature of this e....

  14. Systematic approach to understanding the pathogenesis of systemic sclerosis.

    Science.gov (United States)

    Zuo, Xiaoxia; Zhang, Lihua; Luo, Hui; Li, Yisha; Zhu, Honglin

    2017-10-01

    Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc. This review aims to provide important information for disease identification, therapeutic targets and potential biomarkers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cardio-pulmonary involvement in systemic sclerosis: A study at a tertiary care center

    Directory of Open Access Journals (Sweden)

    Geetakiran Arakkal

    2017-01-01

    Conclusions: In our patients, pulmonary involvement was more common than cardiac involvement. Interstitial lung disease and cardiac involvement were more commonly seen in diffuse systemic sclerosis whereas pulmonary hypertension was more frequent in limited systemic sclerosis. Hence, it is important to screen the patients for cardiopulmonary involvement for early diagnosis and treatment and a better prognostic outcome.

  16. Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

    NARCIS (Netherlands)

    Denton, Christopher P.; Krieg, Thomas; Guillevin, Loic; Schwierin, Barbara; Rosenberg, Daniel; Silkey, Mariabeth; Zultak, Maurice; Matucci-Cerinic, Marco; Stetter, M.; Lackner, K.; Tomi, N.; Hafner, F.; Brodmann, M.; Kuen-Spiegel, M.; Kolle, H.; Raffier, B.; Hamberger, N.; Metz, S.; Siebel, C.; Trummer, M.; Thonhofer, R.; Illmer, X.; Trautinger, F.; Schmidt, P.; Rintelen, B.; Sautner, J.; Willfort-Ehringer, A.; Margeta, C.; Monshi, B.; Pirkhammer, D.; Richter, L.; Holzer, G.; Minmair, G.; Broll, H.; Takacs, M.; Hirschl, M.; Mesaric, P.; Feldmann, R.; Semmelweis, K.; Hundstorfer, M.; Reinhart, V.; Maurer, B.; Verner, D.; Distler, O.; Schmidt-Bosshard, R.; Bohmova, J.; Prochazkova, L.; Nemec, P.; Fojtik, Z.; Soukup, T.; Smrzova, A.; Suchy, D.; Zemanova, I.; Becvar, R.; Gawlik, A.; Koch, M.; Rauen, T.; Voss, B.; Kurthen, R.; Unholzer, A.; Starz, H.; Welzel, J.; Plaumann, K.; Merk, B.; Bloching, H. H.; Moosig, F.; Frey, P.; Kahl, S.; Schleenbecker, H.; Storck-Mueller, K.; Schwarting, A.; Hazenbiller, A.; Nichelmann, V.; Flaig, W.; Rumbaur, C.; Boesenberg, I.; Schmeiser, T.; Marx, J.; Mayer, L.; Stein, T.; Ochs, W.; Rasche, C.; Worm, M.; Riemekasten, G.; Deuschle, K.; Becker, M.; Kleiner, H. J.; Schulze, K.; Tiggers, C.; Peters, J.; Kirschke, J.; Schaefer, C.; Monshausen, M.; Mengden, T.; Sadeghlar, F.; Seidel, M.; Hillebrecht, C.; Andresen, J.; Reemtsen, R.; Stoeckl, F.; Sperling, S.; Podda, M.; Wagner, N.; Guenzel, J.; Wuerzburg, I.; Luethke, K.; Enderlein, M.; Kayser, M.; Gerber, A.; Haust, M.; Hoff, N. P.; Mota, R.; Akanay-Diesel, S.; Jahnke, K.; Mettler, S.; Toeller, S.; Zwenger, S.; Klein, E.; Hahn, K.; Beyer, C.; Distler, J.; Katzemich, A.; Erfurt-berge, C.; Sticherling, M.; Schuch, F.; Rapp, P.; Mitchell, A.; Freundlieb, C.; Rushentsova, U.; Himsel, A.; Henkemeier, U.; Eilbacher, P.; Ullrich-Guenther, C.; Neul, S.; Oelsner, M.; Hermanns, G.; Fiene, M.; Gause, A.; Mensing, C.; Klings, D.; Mensing, H.; Messall, J.; Zuper, R.; May, D.; Bruckner, L.; Sheikh, N.; Aries, P.; Kirchberg, S.; Funkert, A.; Blank, N.; Lupaschko, S.; Schwuerzer-Voit, M.; Meier, L.; Herr, U.; Meier, U.; Neek, G.; Wernitzsch, H.; Pfoehler, C.; Assmann, G.; Vosswinkel, J.; Krog, B.; Wollersdorfer, E.; Oltmann-Schroeder, J.; Zeuner, R.; Uhlig, S.; Barth, S.; Huegel, R.; Glaeser, R.; Rabe, B.; Schuster, J.; Scholz, J.; Kremer, K.; Robakidze-Torbahn, M.; Moinzadeh, P.; Mittag, M.; Dohse, A.; Muhlack, A.; Schultz, L.; Schult, S.; Frambach, Y.; Kettenbach, A.; Fell, I.; Schweda, K.; Steinbrink, K.; Podobinska, M.; Harmuth, W.; Nielen, C.; Kaczmarczyk, A.; Kellner, C.; von Oelhafen, J.; von Bildering, P. B.; Kunze, S.; Niedermeier, A.; Messer, G.; Sardy, M.; Bekou, V.; Belloni, B.; Huettig, B.; Ziai, M.; Hein, R.; Hallecker, A.; Gaubitz, M.; Hallermann, C.; Schmidt, K.; Herrgott, I.; Hildebrandt, B.; Eiden, E.; Guertler, I.; Gernot Scheibl, E.; Brand, H.; Kaeding, U.; Weiss, E.; Reischel, N.; Kern, S.; Baumann, C.; Hellmich, B.; Loeffler, C.; Pflugfelder, J.; Karaenke, P.; Ruchenburg, J.; Blume, J.; Zabel, M.; Deppermann, N.; Chromik, S.; Metzler, C.; Krupp, E.; Rumpel, H.; Krause Rostock, J.-O.; Kneitz, C.; Federow, I.; Schneider, K.; Semmler, M.; Hapke, S.; Barnd, A.; Linke, M.; Kampe-Juzak, E.; Knoebel, K.; Niefanger, K.; Wilhelm, H. U.; Lauterwein, B.; Fierlbeck, G.; Schanz, S.; Pfeiffer, C.; Hassel, R.; Wahn, H.; Schildt, K.; von Elling, A.; Boro, D.; Ebel, J.; Ahmadi, K.; Moritz, D.; Dietl, S.; Dyballa, J.; Alsheimer, B.; Schuetz, N.; Schuart, T.; Mueglich, C.; Tony, H. P.; Marina, P.; Deininger, F.; Hartmann, F.; Olsen, A. B.; Sondergaard, K. H.; Naderi, Y.; Iversen, L. V.; Karlsmark, T.; Knudsen, J. B.; Gil, J. G.; Lopez, J. C. F.; Tasende, J. A. P.; Gonzales, M. F.; Sandoval, A. A.; del Carmen Torres Martin, M.; Corteguera, M.; Barca, B. A.; Montes, I. C.; de la Torre, R. G.; Victoria Egurbide, M.; Pros, A.; Munoz, J.; Simeon, C. P.; Espinosa, G.; Espinposa, G.; Rodriguez, M. A. P.; Castellvi, I.; Mascaro, J. M.; Bellido, D.; Manzanedo, V. S.; Huertas, M. P.; Sanchez, M. D. M.; Trenado, M. S. S.; Garcia, P. V.; Gines Martinez, F.; Angeles Aquirre, M.; del Rio, A. H.; Vazquez, J. L. G.; Coleman, J. V.; Lopez, M. R.; Sanchez, P. S.; Aizpuru, E. M. F.; Mateo, F. J. N.; Callejas, J. L.; Ortego, N.; Santo, M. P.; Rubio, M.; Martin, I.; Cruz, A.; Crespo, M.; Ramos, P. C.; Fernandez, A. S.-A.; Filloy, J. A. M.; Rodriguez, T. R. V.; Marhuenda, A. R.; Blanco, J. J. R.; Hernan, M. G. B.; Mendoza, A. Z.; de la Puente, C.; Rabaneda, E. V.; de Vicuna, R. G.; del Mar Ripoll Macias, M.; del la Pena Lefebvre, P. G.; de Ramon, E.; Camps, M. T.; Fernandez, C.; Miguelez, R.; Uson, J.; Delgado, E. G.; Villaverde, V.; Maceiras, F.; Cruz, J.; Mosquera, J. A.; Mera, A.; Pampin, E. P.; Blanco, J. S.; Maneiro, J. R.; Diaz, J. J.; Losada, L.; Caamano, M.; Fernandez, S.; Insua, S. A.; Laurin, C. U.; Sanchez, J.; Fernandez, N. C.; Becerra, N. D.; Garcia, A.; Nicolas, G. M.; del Carmen Ortega de la O, M.; Rueda, A.; Calvo, J.; Roman Ivorra, J.; Sancho Alegre, J. J.; Barbado, J.; Montes, J.; Saez, L.; Kaarto, A.; Makinen, H.; Madaule, S.; Dadban, A.; Lok, C.; Ferrandiz, D.; Moiton, M. P.; Magy-Bertrand, N.; Taieb, A.; Droitcourt, C.; Belin, E.; Balquiere, S.; Prey, S.; Boulon, C.; Constans, J.; Richez, C.; Sassolas, B.; Misery, L.; Greco, M.; collet, E.; Berthier, S.; Leguy-Seguin, V.; Imbert, B.; Carpentier, P.; Blaise, S.; Maillard, H.; Beneton, N.; Launay, D.; Hachulla, E.; Woijtasik, G.; Charlanne, H.; Lambert, M.; Jourdain, N.; Hatron, P. Y.; Morell, S.; Spars, A.; Couraud, A.; Doeffel-hantz, V.; Fauchais, A. L.; Vidal, E.; Goudran, G.; Bezanahary, H.; Boussely, N.; Manea, P.; Dumonteil, S.; Loustaud-ratti, V.; Hot, A.; Coppere, B.; Desmurs-Clavel, H.; Ninet, J.; Girard-Madoux, M. H.; Granel, B.; Keynote, A.; Khau van Kien, A.; Rullier, P.; Le Quellec, A.; Riviere, S.; Bessis, D.; Cohen, J. D.; Farcas, C.; Granel-brocard, F.; Agard, C.; Durant, C.; Fuzibet, J. G.; Queyrel, V.; Berezne, A.; Guillevin, L.; Mouthon, L.; Frances, C.; Toledano, C.; Cabane, J.; Tiev, K.; Farge, D.; Keshtmand, H.; Lazareth, I.; Priollet, P.; Michon-Pasturel, U.; Wipff, J.; Assous, N.; Cartry, O.; Kostrzwewa, E.; Doutre, M. S.; Blum, L.; Reguiai, Z.; Letremy, A.; Perlat, A.; Cazalets-lacoste, C.; Decaux, O.; Jego, P.; Duval-modeste, A. B.; Deboves, O.; Sordet, C.; Chatelus, E.; Chiffot, H.; Sibillia, J.; Couret, B.; Moulis, G.; Sailler, L.; Adoue, D.; Gaches, F.; Diot, E.; Skowron, F.; Zenone, T.; Quemeneur, T.; Kyndt, X.; Wahl, D.; Zuily, S.; Moline, T.; Bravetti, V.; Galanopoulos, N.; Vasilopoulos, D.; Vlachoyannopoulos, P.; Kritikos, I.; Tsifetaki, N.; Koutroumbas, A.; Garyfallos, A.; Athanassiou, P.; Aslanidis, S.; Kamali, S.; Dimitroulas, T.; Galanopoulo, V.; Elezoglou, A.; Grier, A.; Murray, M.; O'Rourke, M.; Gabrielli, A.; Lapadula, G.; Serafino, L.; Terlizzi, N.; Bellissimo, S.; Stisi, S.; Malavolta, N.; Airo, P.; Vacca, A.; Battaglia, E.; Foti, R.; Mazzuca, S.; Bortoluzzi, A.; Trotta, F.; Galluccio, F.; Marucci, A.; Cantatore, F.; Bucci, R.; Puppo, F.; de Angeli, R.; Grassi, W.; Cipriani, P.; Mazzone, A.; Faggioli, P.; Severino, A.; Scorza, R.; Belloli, L.; Ughi, N.; Antivalle, M.; del Papa, N.; Maglione, W.; Zeni, S.; Ferri, C.; Colaci, M.; Varcasia, G.; Cuomo, G.; Cozzi, F.; Triolo, G.; Gatti, S.; Montecucco, C. M.; Doveri, M.; Nigro, A.; Olivieri, I.; Bajoochi, G.; Rosato, E.; Salsano, F.; Faustini, F.; Ferraccioli, G.; Colonna, L.; Pallotta, S.; Riccieri, V.; Mussi, A.; Bellisai, F.; Galeazzi, M.; Fusaro, E.; Saracco, M.; Pellerito, R.; Masolini, P.; de Vita, S.; Lombardi, S.; Lunardi, C.; Moolenburgh, J. D.; Heurkens, A. H. M.; Voskuyl, A.; Hak, A. E.; Stroes, E. S. K.; Remans, J.; Gerdes, V.; van Woerkom, J. M.; de Long, A. J. L.; Kaasjager, H. A. H.; Visser, H.; Janssen, M.; van Guldener, C.; van Neer, F.; Vos, P.; Peters, A. J.; Hulsmans, H.; Ronday, K.; Goekoop, R.; Ewals, J.; Valentijn, R.; de Bois, M.; Westedt, M. L.; Siewertsz van Reesema, D.; Knifjj-Dutmer, E.; Stolk, J. N.; Willems, H.; Kuiper-geertsma, D. G.; Baudaoin, P.; Fretter, P.; Westra, R.; Sonnaville, P. B. J.; Smit, A.; Bootsma, H.; Brouwer, L.; Bijl, M.; Molders, N.; Lebrun, C.; van der Veen, M. J.; Noordzij, M.; Houben, H.; Landewe, R. M. B.; Vercoutere, W.; Jahangier de Veen, Z. N.; Zijlstra, T. R.; Ubels, F.; Bruyn, G.; Jansen, P.; Schuerwegh, A.; Huizinga, T. W. J.; Paassen, P.; Hurkens, T.; Geurts, M.; van den Hoogen, F.; Vonk, M.; Jacobs, P. J. C.; Groenendael, J. H. L. M.; Seys, P.; van Zeben, D.; van Paassen, H.; Groenendael, J.; Han, K. H.; Wlarvens, M.; van Hagen, M.; van Daele, P.; Dolhain, R.; Gerards, A. H.; van der Lubbe, P.; Kanter, M. D. E.; Muller, W. H.; Ton, E.; van Krugten, M.; van Gameren, I.; Lanting, P.; den Hengst, C.; Gjessdal, C. G.; Hjertaker, S. L.; Madland, T. M.; Bendvold, A.; Bitter, H.; Hoffmann-Vold, A. M.; Midtvedt, O.; Bakland, G.; Aslkaksen, H. K.; Seip, M.; Kalstad, S.; Koldingsnes, W.; Grandauent, B.; Nordvag, B. Y.; Stran, E. K.; Skomsvoll, J.; Andersen, M.; Thomsen, R. S.; Pedersen, T.; Bakkeheim, V.; Cordeiro, A.; Alves, J.; Oliveira, S.; Coelho, P.; Resende, C.; Ponte, C.; Almeida, I.; Silva, I.; Santos, C.; Camara, I.; Costa, J.; Hellstrom, H.; Mohammad, A.; Lind, I.; Lind, K.; Bracin, T.; Liljequist, E.; Vingren, T.; Ostenson, A.; Hermansson, E.; Thorsson, C.; Soderlin, M.; Nordin, A.; Waldheim, E.; Vengemyr, K.; Albertsson, K.; Karlsson, M. L.; Rydvald, Y.; Rizk, M.; Dolnicar, A. S.; Lukac, J.; James, J.; McHugh, N.; Cole, S.; Brown, S.; Hamilton, A.; Faizal, A.; Hall, F.; Murphy, K.; Skingle, S.; Harris, H.; Madhok, F.; Hampson, R.; Baguley, E.; Ogunbambi G, O.; Lamb, J.; Anderson, M.; Moots, R.; White-Alao, B.; Morrison, C.; Dobson, J.; Gordon, P.; Salerno, R.; Denton, C.; Parker, L.; Ochiel, R.; Vincent, R.; Zimba, S.; Ngcozana, T.; Xu, Y.; D'Cruz, D.; Choong, L. M.; Herrick, A.; Wragg, E.; Manning, J.; Moore, T.; Kelsey, C.; Chakravarty, K.; Skyes, H.; Athiveer, P.

    2012-01-01

    The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). The DUO Registry is a European, prospective, multicentre, observational, registry of SSc

  17. Nailfold video-capillaroscopy in systemic sclerosis.

    Science.gov (United States)

    Cutolo, M; Pizzorni, C; Sulli, A

    2004-12-01

    The Raynaud's phenomenon (RP) is the most common and significant clinical condition supporting microvascular analysis as soon as possible. Microvascular involvement is a key feature of RP, and several rheumatic diseases are characterized by the presence of the RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, noninvasive and inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been described mainly in scleroderma (SSc) patients complaining of a secondary RP. The peripheral microvascular damage in SSc is characterized by increasing structural alterations of the capillaries (giant capillaries and microhemorrhages) with progressive decrease of their density. The detection of the scleroderma NCV allows early differentiation between primary RP (functional, not disease associated), and secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NCV and the clinical symptoms, severity of the disease and the laboratory findings. Further clinical and epidemiological studies, as well as a standardized and computerized quantitation of the observed damages are required.

  18. Aortic pulse wave velocity measurement in systemic sclerosis patients

    Directory of Open Access Journals (Sweden)

    M. Sebastiani

    2012-12-01

    Full Text Available Background. Systemic sclerosis (SSc is characterized by endothelial dysfunction and widespread microangiopathy. However, a macrovascular damage could be also associated. Aortic pulse wave velocity (aPWV is known to be a reliable indicator of arterial stiffness and a useful prognostic predictor of cardiovascular events. Moreover, aPWV may be easily measured by non-invasive, user-friendly tool. Aim of our study was to evaluate aPWV alterations in a series of SSc patients. Methods. The aPWV was evaluated in 35 consecutive female SSc patients and 26 sex- and age-matched healthy controls. aPWV alterations were correlated with cardiopulmonary involvement. Results. A significant increase of aPWV was observed in SSc patients compared to controls (9.4±3.2 m/s vs 7.3±1 m/s; P=0.002. In particular, 14/35 (40% SSc patients and only 1/26 (4% controls (P=0.0009 showed increased aPWV (>9 m/s cut-off value. Moreover, echocardiography evaluation showed an increased prevalence of right atrial and ventricular dilatation (atrial volume: 23.6±6.2 mL vs 20.3±4.3 mL, P=0.026; ventricular diameter 19.5±4.9 mm vs 15.9±1.6 mm; P=0.001 associated to higher values of pulmonary arterial systolic pressure (PAPs in SSc patients (31.5±10.4 mmHg vs 21.6±2.9 mmHg; P50 years old. Furthermore, altered aPWV was more frequently associated with limited cutaneous pattern, longer disease duration (≥5 years, and/or presence of anticentromere antibody (ACA. Conclusions. A significantly higher prevalence of abnormally increased aPWV was evidenced in SSc patients compared to healthy controls. The possibility of more pronounced and diffuse vascular damage in a particular SSc subset (ACA-positive subjects with limited cutaneous scleroderma and longer disease duration might be raised.

  19. Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Polona Lavtar

    Full Text Available Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized that this fact might be partially associated with the influence of latitude on circadian rhythm and consequently that genetic variability of key circadian rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian patients and 1024 healthy controls were compared for genetic signature at 8 SNPs, 4 for each of both genes. We found a statistically significant difference in genotype (ARNTL rs3789327, P = 7.5·10-5; CLOCK rs6811520 P = 0.02 distributions in patients and controls. The ARNTL rs3789327 CC genotype was associated with higher risk for multiple sclerosis at an OR of 1.67 (95% CI 1.35-2.07, P = 0.0001 and the CLOCK rs6811520 genotype CC at an OR of 1.40 (95% CI 1.13-1.73, P = 0.002. The results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis.

  20. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    NARCIS (Netherlands)

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  1. Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis

    DEFF Research Database (Denmark)

    Wirz, Elina G; Jaeger, Veronika K; Allanore, Yannick

    2016-01-01

    OBJECTIVES: To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. METHODS...

  2. Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Necla Keskin

    2013-08-01

    Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

  3. Multiple Sclerosis: associated cardiometabolic risks and impact of exercise therapy

    OpenAIRE

    Jacobs, Jasper

    2016-01-01

    Multiple sclerosis (MS) is characterized by complex heterogeneous symptoms, which often leads to a more sedentary lifestyle. This lifestyle increases the likelihood to develop secondary health problems, like cardiometabolic risk (CMR) profile. However, in other population these secondary health problems can be, partly, reversed by exercise therapy. We hypothesized that MS affects the CMR profile, but the outcome can be reversed following exercise therapy. Persons with MS and matched healthy c...

  4. Esclerose sistêmica e níveis séricos elevados de organoclorado: uma associação possível? Systemic sclerosis and elevated organochlorine blood levels: a possible association?

    Directory of Open Access Journals (Sweden)

    Odirlei André Monticielo

    2008-02-01

    Full Text Available A patogênese da esclerose sistêmica (ES é complexa e pouco conhecida. Há a participação de ativação imune, dano vascular e excessiva produção de matriz extracelular com deposição de colágeno estruturalmente normal. Fatores genéticos e ambientais contribuem para a expressão da doença nos pacientes. Dentre os fatores ambientais, diversos agentes químicos já foram associados à doença. Descrevemos o caso de uma adolescente de 16 anos, com história prévia de hepatite criptogênica e câncer de lábio, que desenvolveu quadro atípico e rapidamente progressivo de esclerose sistêmica. Inicialmente o quadro era compatível com esclerodermia em placas, porém rapidamente evoluiu para uma forma sistêmica com grave acometimento cardiopulmonar e óbito. Durante a investigação de possíveis fatores etiológicos que pudessem estar relacionados, foram encontrados níveis séricos extremamente elevados de oxiclordano, um agrotóxico organoclorado. Uma possível correlação entre a intoxicação por esse agente químico e o surgimento de ES foi aventada.The pathogenesis of systemic sclerosis (SS is complex and not completely understood. Autoimmune mechanisms, vascular damage, and excessive extracelular matrix with collagen deposition play a significant role. Genetic and environmental factors also are decisive to the disease expression. Among environmental factors many chemical agents have been associated with the development of SS. A 16-year-old white woman, with previous history of cryptogenic hepatitis and cancer of the lips, developed an atypical and rapidly progressive form of SS. Initial sclerodermatous plaques progressed to a systemic form with severe cardiopulmonary involvement and death. Diagnostic workup revealed extremely high blood levels of oxychlordane. A possible association of organochlorine intoxication and SS is proposed.

  5. Pneumatosis Intestinalis as the Initial Presentation of Systemic Sclerosis: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Farshid Ejtehadi

    2012-01-01

    Full Text Available Introduction. Pneumatosis intestinalis (PI is an uncommon pathology characterised by the presence of gas within the intestinal wall. It has been associated with various conditions, including connective tissue diseases. This is the first report of PI being the initial presentation of systemic sclerosis. Case Presentation. The patient, a 75-year-old female, presented with an 8-month history of worsening dysphagia and epigastric pain, as well as other nonspecific symptoms. Initial investigations with an oesophagogastroduodenoscopy diagnosed Candida oesophagitis and also identified an extrinsic compression of the gastric antrum. Subsequently a CT scan of the abdomen and pelvis showed moderately dilated small bowel loops and PI. Due to the patient’s stability, non-critical clinical condition, conservative management was instituted. More detailed investigations confirmed the diagnosis of systemic sclerosis with positive anticentromeric and antinuclear antibodies. The patient improved on methotrexate and was discharged with appropriate outpatient follow-up. Discussion. PI is a rare but well-documented pathology associated with connective tissue diseases, such as systemic sclerosis. In most cases, conservative management is preferable to surgical intervention, depending on the patient’s clinical presentation and progress. This is the first report of PI being the initial presentation of a patient with systemic sclerosis responsive to conservative management.

  6. Associations of Systemic Diseases with Intermediate Uveitis.

    Science.gov (United States)

    Shoughy, Samir S; Kozak, Igor; Tabbara, Khalid F

    2016-01-01

    To determine the associations of systemic diseases with intermediate uveitis. The medical records of 50 consecutive cases with intermediate uveitis referred to The Eye Center in Riyadh, Saudi Arabia, were reviewed. Age- and sex-matched patients without uveitis served as controls. Patients had complete ophthalmic and medical examinations. There were 27 male and 23 female patients. Mean age was 29 years with a range of 5-62 years. Overall, 21 cases (42%) had systemic disorders associated with intermediate uveitis and 29 cases (58%) had no associated systemic disease. A total of 11 patients (22%) had asthma, 4 (8%) had multiple sclerosis, 3 (6%) had presumed ocular tuberculosis, 1 (2%) had inflammatory bowel disease, 1 (2%) had non-Hodgkin lymphoma and 1 (2%) had sarcoidosis. Evidence of systemic disease was found in 50 (5%) of the 1,000 control subjects. Bronchial asthma was found in 37 patients (3.7 %), multiple sclerosis in 9 patients (0.9%), inflammatory bowel disease in 3 patients (0.3%), and tuberculosis in 1 patient (0.1%). None of the control patients had sarcoidosis or lymphoma. There were statistically significant associations between intermediate uveitis and bronchial asthma (p = 0.0001), multiple sclerosis (p = 0.003) and tuberculosis (p = 0.0005). Bronchial asthma and multiple sclerosis were the most frequently encountered systemic diseases associated with intermediate uveitis in our patient population. Patients with intermediate uveitis should undergo careful history-taking and investigations to rule out associated systemic illness.

  7. Somatosensory impairment and its association with balance limitation in people with multiple sclerosis.

    Science.gov (United States)

    Jamali, Akram; Sadeghi-Demneh, Ebrahim; Fereshtenajad, Niloufar; Hillier, Susan

    2017-09-01

    Somatosensory impairments are common in multiple sclerosis. However, little data are available to characterize the nature and frequency of these problems in people with multiple sclerosis. To investigate the frequency of somatosensory impairments and identify any association with balance limitations in people with multiple sclerosis. The design was a prospective cross-sectional study, involving 82 people with multiple sclerosis and 30 healthy controls. Tactile and proprioceptive sensory acuity were measured using the Rivermead Assessment of Somatosensory Performance. Vibration duration was assessed using a tuning fork. Duration for the Timed Up and Go Test and reaching distance of the Functional Reach Test were measured to assess balance limitations. The normative range of sensory modalities was defined using cut-off points in the healthy participants. The multivariate linear regression was used to identify the significant predictors of balance in people with multiple sclerosis. Proprioceptive impairments (66.7%) were more common than tactile (60.8%) and vibration impairments (44.9%). Somatosensory impairments were more frequent in the lower limb (78.2%) than the upper limb (64.1%). All sensory modalities were significantly associated with the Timed Up and Go and Functional Reach tests (plimitation. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The Gas6/TAM System and Multiple Sclerosis.

    Science.gov (United States)

    Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

    2016-10-28

    Growth arrest specific 6 (Gas6) is a multimodular circulating protein, the biological actions of which are mediated by the interaction with three transmembrane tyrosine kinase receptors: Tyro3, Axl, and MerTK, collectively named TAM. Over the last few decades, many progresses have been done in the understanding of the biological activities of this highly pleiotropic system, which plays a role in the regulation of immune response, inflammation, coagulation, cell growth, and clearance of apoptotic bodies. Recent findings have further related Gas6 and TAM receptors to neuroinflammation in general and, specifically, to multiple sclerosis (MS). In this paper, we review the biology of the Gas6/TAM system and the current evidence supporting its potential role in the pathogenesis of MS.

  9. Correlation between serum E-selectin levels and panoramic nailfold capillaroscopy in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Valim V.

    2004-01-01

    Full Text Available E-selectin is expressed by the activated endothelium and its plasma levels are increased in patients with systemic sclerosis. Eighteen patients fulfilling the American Rheumatism Association criteria for systemic sclerosis, 15 females and 3 males, 42-70 years old, 9 with diffuse and 9 with limited forms, were sequentially recruited for this study. Serum E-selectin levels were determined by commercially available ELISA and their association with nailfold capillaroscopic abnormalities was investigated. Nailfold capillaries were analyzed by 16X magnification wide-field capillaroscopy. Two parameters on capillaroscopy were used to correlate to serum E-selectin: deletion and ectasia. Data were analyzed statistically by the Student t-test and Spearman correlation. Two-tailed P values below 0.05 were considered significant. E-selectin range was 38 to 200 ng/ml (80 ± 39.94. There was a correlation between serum E-selectin levels and the deletion capillaroscopic score (r = 0.50, P < 0.035. This correlation was even stronger within the first 48 months of diagnosis (r = 0.63, P < 0.048. On the other hand, no association was observed between selectin and ectasia. Patients with diffuse disease presented higher serum E-selectin levels than patients with limited disease, although the difference was not statistically significant (96.44 ± 48.04 vs 63.56 ± 21.77 ng/dl; P = 0.08. The present study is the first showing a correlation between soluble serum E-selectin levels and alterations in capillaroscopy. The stronger correlation of deletion score in capillaroscopy in early disease suggests that serum E-selectin levels might be a useful biochemical marker of disease activity in systemic sclerosis.

  10. Correlation between serum E-selectin levels and panoramic nailfold capillaroscopy in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    V. Valim

    2004-09-01

    Full Text Available E-selectin is expressed by the activated endothelium and its plasma levels are increased in patients with systemic sclerosis. Eighteen patients fulfilling the American Rheumatism Association criteria for systemic sclerosis, 15 females and 3 males, 42-70 years old, 9 with diffuse and 9 with limited forms, were sequentially recruited for this study. Serum E-selectin levels were determined by commercially available ELISA and their association with nailfold capillaroscopic abnormalities was investigated. Nailfold capillaries were analyzed by 16X magnification wide-field capillaroscopy. Two parameters on capillaroscopy were used to correlate to serum E-selectin: deletion and ectasia. Data were analyzed statistically by the Student t-test and Spearman correlation. Two-tailed P values below 0.05 were considered significant. E-selectin range was 38 to 200 ng/ml (80 ± 39.94. There was a correlation between serum E-selectin levels and the deletion capillaroscopic score (r = 0.50, P < 0.035. This correlation was even stronger within the first 48 months of diagnosis (r = 0.63, P < 0.048. On the other hand, no association was observed between selectin and ectasia. Patients with diffuse disease presented higher serum E-selectin levels than patients with limited disease, although the difference was not statistically significant (96.44 ± 48.04 vs 63.56 ± 21.77 ng/dl; P = 0.08. The present study is the first showing a correlation between soluble serum E-selectin levels and alterations in capillaroscopy. The stronger correlation of deletion score in capillaroscopy in early disease suggests that serum E-selectin levels might be a useful biochemical marker of disease activity in systemic sclerosis.

  11. Coexistence of systemic lupus erythematosus and multiple sclerosis. A case report and literature review.

    Science.gov (United States)

    Jácome Sánchez, Elisa Carolina; García Castillo, María Ariana; González, Victor Paredes; Guillén López, Fernando; Correa Díaz, Edgar Patricio

    2018-01-01

    Multiple sclerosis (MS) and systemic lupus erythematous (SLE) are autoimmune diseases, the coexistence of which is uncommon in patients. Owing to the rarity of this condition, the distinction between MS and SLE is a diagnostic challenge for neurologists. We present a case report in which MS and SLE were present in the same patient. There are few case reports in the world on the association between MS and SLE. The following case report is the first of its kind in which both MS and SLE are present in a patient from a country with low prevalence of MS such as Ecuador.

  12. Bilateral vocal fold immobility in a patient with overlap syndrome rheumatoid arthritis/systemic sclerosis.

    Science.gov (United States)

    Ingegnoli, Francesca; Galbiati, Valentina; Bacciu, Andrea; Zeni, Silvana; Fantini, Flavio

    2007-10-01

    Bilateral vocal fold immobility (BVFI) can be the result of a primary disorder or as an iatrogenic complication of surgery or intubation. Laryngeal involvement can be a rare complication of connective tissue disorders and it usually occurs in association with other symptoms and signs that indicate active disease. We present a case of BVFI in a patient with an overlap syndrome rheumatoid arthritis/systemic sclerosis, referred to our division because of dysphonia and dyspnea. The video-laryngostroboscopy showed the presence of BVFI. Physical examination, blood tests, lung and neck high resolution computed tomography scans did not demonstrate significant abnormalities. She was treated with pulses of intravenous methylprednisolone with slow improvement.

  13. CUTANEOUS MYXOID CYST ON THE SCLEROTIC FINGER IN A PATIENT WITH DIFFUSE SYSTEMIC SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Taeko Nakamura-Wakatsuki

    2013-10-01

    Full Text Available Skin tumors occurring on the scleroderma fingers are rarely seen. Swollen fingers are hallmarks of systemic sclerosis, and mucin deposition in the lesional skin is a constant feature in systemic sclerosis. Here we describe a case of cutaneous myxoid cyst on the flexor aspect of the sclerotic fingers in a patient with severe diffuse cutaneous systemic sclerosis. Cutaneous myxoid cyst is a relatively common benign tumor; however, cases of cutaneous myxoid cysts developing on the scleroderma fingers have not been reported to date. Mucin deposition in the sclerotic skin may be a predisposing factor in the induction of myxoid cyst on the scleroderma finger in our patient.

  14. Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report.

    Science.gov (United States)

    Tokman, S; Hays, S R; Leard, L E; Bush, E L; Kukreja, J; Kleinhenz, M E; Golden, J A; Singer, J P

    2015-12-01

    Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Registry Evaluation of Digital Ulcers in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Felice Galluccio

    2010-01-01

    Full Text Available Digital ulcers are a very frequent complication of systemic sclerosis affecting about half of the SSc patients, and about 75% of the affected patients have their first DU episode within 5 years from their first non-Raynaud symptom. The lack of adequate classification criteria as well as the lack of knowledge of the development of DU have contributed to the opening of specific registries to better understand the natural history of these lesions. For these reason, specific disease registries play a fundamental role in this field of research. Thanks to the systematic collection of data and their subsequent analysis and comparison between different cohorts, it is possible to improve understanding of the underlying trigger mechanisms of DU development and to determine temporal trends. In the future, the development of recommendations for the management of DU remains of pivotal importance to prevent DU development and obtain rapid healing as well as reduction of pain and disability.

  16. Determinants of mortality in systemic sclerosis: a focused review.

    Science.gov (United States)

    Poudel, Dilli Ram; Jayakumar, Divya; Danve, Abhijeet; Sehra, Shiv Tej; Derk, Chris T

    2017-11-07

    Scleroderma (systemic sclerosis) is an autoimmune rheumatic disorder that is characterized by fibrosis, vascular dysfunction, and autoantibody production that involves most visceral organs. It is characterized by a high morbidity and mortality rate, mainly due to disease-related complications. Epidemiological data describing mortality and survival in this population have been based on both population and observational studies. Multiple clinical and non-clinical factors have been found to predict higher likelihood of death among thepatients. Here, we do an extensive review of the available literature, utilizing the PubMed database, to describe scleroderma and non-scleroderma related determinants of mortality in this population. We found that even though the mortality among the general population has declined, scleroderma continues to carry a very high morbidity and mortality rate, however we have made some slow progress in improving the mortality among scleroderma patients over the last few decades.

  17. From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution.

    Science.gov (United States)

    Dilia, Giuggioli; Michele, Colaci; Emanuele, Cocchiara; Amelia, Spinella; Federica, Lumetti; Clodoveo, Ferri

    2018-01-01

    Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0-156) months. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset.

  18. Cardiac tamponade preceding skin involvement in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    L. Bozzola

    2011-09-01

    Full Text Available The frequency of pericardial involvement in Systemic Sclerosis (SSc is high on autoptic or echocardiographic studies, but the clinical recognition of pericarditis with or without effusion is rare. We describe a case of a 71-year-old female with no previous history of heart disease, who presented with a large pericardial effusion and tamponade that required pericardial drain. She had suffered from Raynaud’s phenomenon since 25 years. Six weeks after hospital discharge she complained of skin hardening on left leg. Pericardial tamponade is a very rare manifestation of SSc and occurs both early or late in the course of the disease, but in our case it preceded the recognition of scleroderma. We have only identified two other cases of pericardial effusion preceding cutaneous involvement in scleroderma.

  19. Comprehensive approach to systemic sclerosis patients during pregnancy.

    Science.gov (United States)

    Rueda de León Aguirre, Alexandra; Ramírez Calvo, José Antonio; Rodríguez Reyna, Tatiana Sofía

    2015-01-01

    Systemic sclerosis (SSc) is a connective tissue disease that usually affects women, with a male:female ratio of 1:4-10. It was thought that there was a prohibitive risk of fatal complications in the pregnancies of patients with SSc. It is now known that the majority of these women undergo a normal progression of pregnancy if the right time is chosen and a close obstetric care is delivered. The obstetric risk will depend on the subtype and clinical stage of the disease, and the presence and severity of the internal organ involvement during the pregnancy. The management of these pregnancies should be provided in a specialized center, with a multidisciplinary team capable of identifying and promptly treating complications. Treatment should be limited to drugs with no teratogenic potential, except when renal crises or severe cardiovascular complications develop. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Kahan, A.; Devaux, J.Y.; Amor, B.

    1986-01-01

    Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined

  1. 'Chronic cerebrospinal venous insufficiency' in multiple sclerosis. Is multiple sclerosis a disease of the cerebrospinal venous outflow system?

    International Nuclear Information System (INIS)

    Wattjes, M.P.; Doepp, F.; Bendszus, M.; Fiehler, J.

    2011-01-01

    Chronic impaired venous outflow from the central nervous system has recently been claimed to be associated with multiple sclerosis (MS) pathology. This resulted in the term chronic cerebrospinal venous insufficiency (CCSVI) in MS. The concept of CCSVI is based on sonography studies showing that impaired venous outflow leading to pathological reflux is almost exclusively present in MS patients but not in healthy controls. Based on these findings, a new pathophysiological concept has been introduced suggesting that chronic venous outflow obstruction and venous reflux in the CNS result in pathological iron depositions leading to inflammation and neurodegeneration. The theory of CCSVI in MS has rapidly generated tremendous interest in the media and among patients and the scientific community. In particular, the potential shift in treatment concepts possibly leading to an interventional treatment approach including balloon angioplasty and venous stent placement is currently being debated. However, results from recent studies involving several imaging modalities have raised substantial concerns regarding the CCSVI concept in MS. In this review article, we explain the concept of CCSVI in MS and discuss this hypothesis in the context of MS pathophysiology and imaging studies which have tried to reproduce or refute this theory. In addition, we draw some major conclusions focusing in particular on the crucial question as to whether interventional treatment options are expedient. In conclusion, the present conclusive data confuting the theory of CCSVI in MS should lead to reluctance with respect to the interventional treatment of possible venous anomalies in MS patients. (orig.)

  2. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  3. Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, M. B.; Haentjens, P.; Nagels, G.; Garmyn, M.; De Keyser, J.

    Background: Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS). Objective: We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS. Methods: We conducted a survey among persons with MS, registered by the Flemish MS

  4. Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles

    DEFF Research Database (Denmark)

    Mero, Inger-Lise; Gustavsen, Marte W; Sæther, Hanne S

    2013-01-01

    The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS). We applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating...

  5. Associations of alcohol consumption with clinical and MRI measures in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, Marie B.; De Keyser, Jacques

    Evaluation of: Foster M, Zivadinov R, Weinstock-Guttman B et al. Associations of alcohol consumption with clinical and MRI measures in multiple sclerosis. J. Neuroimmunol. 243(1-2), 61-68 (2012). While the harmful effects of alcohol abuse are well documented, experimental and clinical data support a

  6. A survey of endogenous retrovirus (ERV) sequences in the vicinity of multiple sclerosis (MS)-associated single nucleotide polymorphisms (SNPs).

    Science.gov (United States)

    Brütting, Christine; Emmer, Alexander; Kornhuber, Malte; Staege, Martin S

    2016-08-01

    Although multiple sclerosis (MS) is one of the most common central nervous system diseases in young adults, little is known about its etiology. Several human endogenous retroviruses (ERVs) are considered to play a role in MS. We are interested in which ERVs can be identified in the vicinity of MS associated genetic marker to find potential initiators of MS. We analysed the chromosomal regions surrounding 58 single nucleotide polymorphisms (SNPs) that are associated with MS identified in one of the last major genome wide association studies. We scanned these regions for putative endogenous retrovirus sequences with large open reading frames (ORFs). We observed that more retrovirus-related putative ORFs exist in the relatively close vicinity of SNP marker indices in multiple sclerosis compared to control SNPs. We found very high homologies to HERV-K, HCML-ARV, XMRV, Galidia ERV, HERV-H/env62 and XMRV-like mouse endogenous retrovirus mERV-XL. The associated genes (CYP27B1, CD6, CD58, MPV17L2, IL12RB1, CXCR5, PTGER4, TAGAP, TYK2, ICAM3, CD86, GALC, GPR65 as well as the HLA DRB1*1501) are mainly involved in the immune system, but also in vitamin D regulation. The most frequently detected ERV sequences are related to the multiple sclerosis-associated retrovirus, the human immunodeficiency virus 1, HERV-K, and the Simian foamy virus. Our data shows that there is a relation between MS associated SNPs and the number of retroviral elements compared to control. Our data identifies new ERV sequences that have not been associated with MS, so far.

  7. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Oey, P.L.; Vos, P.E.; Wieneke, G.H.; Wokke, J.H.J.; Blankestijn, P.J.; Karemaker, J.M.

    2002-01-01

    The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

  8. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Oey, P. Liam; Vos, Pieter E.; Wieneke, George H.; Wokke, John H. J.; Blankestijn, Peter J.; Karemaker, John M.

    2002-01-01

    The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

  9. A system out of breath: how hypoxia possibly contributes to the pathogenesis of systemic sclerosis.

    NARCIS (Netherlands)

    Hal, T.W. van; Bon, L. van; Radstake, T.R.D.J.

    2011-01-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially

  10. Designing an Electronic Patient Management System for Multiple Sclerosis: Building a Next Generation Multiple Sclerosis Documentation System.

    Science.gov (United States)

    Kern, Raimar; Haase, Rocco; Eisele, Judith Christina; Thomas, Katja; Ziemssen, Tjalf

    2016-01-08

    Technologies like electronic health records or telemedicine devices support the rapid mediation of health information and clinical data independent of time and location between patients and their physicians as well as among health care professionals. Today, every part of the treatment process from diagnosis, treatment selection, and application to patient education and long-term care may be enhanced by a quality-assured implementation of health information technology (HIT) that also takes data security standards and concerns into account. In order to increase the level of effectively realized benefits of eHealth services, a user-driven needs assessment should ensure the inclusion of health care professional perspectives into the process of technology development as we did in the development process of the Multiple Sclerosis Documentation System 3D. After analyzing the use of information technology by patients suffering from multiple sclerosis, we focused on the needs of neurological health care professionals and their handling of health information technology. Therefore, we researched the status quo of eHealth adoption in neurological practices and clinics as well as health care professional opinions about potential benefits and requirements of eHealth services in the field of multiple sclerosis. We conducted a paper-and-pencil-based mail survey in 2013 by sending our questionnaire to 600 randomly chosen neurological practices in Germany. The questionnaire consisted of 24 items covering characteristics of participating neurological practices (4 items), the current use of network technology and the Internet in such neurological practices (5 items), physicians' attitudes toward the general and MS-related usefulness of eHealth systems (8 items) and toward the clinical documentation via electronic health records (4 items), and physicians' knowledge about the Multiple Sclerosis Documentation System (3 items). From 600 mailed surveys, 74 completed surveys were returned

  11. Incidence and prevalence of systemic sclerosis in Campo Grande, State of Mato Grosso do Sul, Brazil.

    Science.gov (United States)

    Horimoto, Alex Magno Coelho; Matos, Erica Naomi Naka; Costa, Márcio Reis da; Takahashi, Fernanda; Rezende, Marcelo Cruz; Kanomata, Letícia Barrios; Locatelli, Elisangela Possebon Pradebon; Finotti, Leandro Tavares; Maegawa, Flávia Kamy Maciel; Rondon, Rosa Maria Ribeiro; Machado, Natália Pereira; Couto, Flávia Midori Arakaki Ayres Tavares do; Figueiredo, Túlia Peixoto Alves de; Ovidio, Raphael Antonio; Costa, Izaias Pereira da

    Systemic sclerosis is an autoimmune disease which shows extreme heterogeneity in its clinical presentation and that follows a variable and unpredictable course. Although some discrepancies in the incidence and prevalence rates between geographical regions may reflect methodological differences in the definition and verification of cases, they may also reflect true local differences. To determine the prevalence and incidence of systemic sclerosis in the city of Campo Grande, state capital of Mato Grosso do Sul (MS), Brazil, during the period from January to December 2014. All health care services of the city of Campo Grande - MS with attending in the specialty of Rheumatology were invited to participate in the study through a standardized form of clinical and socio-demographic assessment. Physicians of any specialty could report a suspected case of systemic sclerosis, but necessarily the definitive diagnosis should be established by a rheumatologist, in order to warrant the standardization of diagnostic criteria and exclusion of other diseases resembling systemic sclerosis. At the end of the study, 15 rheumatologists reported that they attended patients with systemic sclerosis and sent the completed forms containing epidemiological data of patients. The incidence rate of systemic sclerosis in Campo Grande for the year 2014 was 11.9 per million inhabitants and the prevalence rate was 105.6 per million inhabitants. Systemic sclerosis patients were mostly women, white, with a mean age of 50.58 years, showing the limited form of the disease with a mean duration of the disease of 8.19 years. Regarding laboratory tests, 94.4% were positive for antinuclear antibody, 41.6% for anti-centromere antibody and 19.1% for anti-Scl70; anti-RNA Polymerase III was performed in 37 patients, with 16.2% positive. The city of Campo Grande, the state capital of MS, presented a lower incidence/prevalence of systemic sclerosis in comparison with those numbers found in US studies and close

  12. Mortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma)

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Halberg, P; Ullman, S

    1998-01-01

    To determine survival, mortality and causes of death in Danish patients with systemic sclerosis (scleroderma), and to analyse how these parameters are influenced by demographic variables and the extent of skin involvement.......To determine survival, mortality and causes of death in Danish patients with systemic sclerosis (scleroderma), and to analyse how these parameters are influenced by demographic variables and the extent of skin involvement....

  13. Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors.

    Science.gov (United States)

    Gargiulo Monachelli, G; Meyer, M; Rodríguez, G E; Garay, L I; Sica, R E P; De Nicola, A F; González Deniselle, M C

    2011-01-01

    Negative prognostic factors in amyotrophic lateral sclerosis include advanced age, shorter time from disease onset to diagnosis, bulbar onset and rapid progression rate. To compare progesterone (PROG) and cortisol serum levels in patients and controls and ascertain its relationship to prognostic factors and survival. We assessed serum hormonal levels in 27 patients and 21 controls. Both hormones were 1.4-fold higher in patients. PROG showed a negative correlation with age, positive correlation with survival and positive trend with time to diagnosis. Increased PROG was observed in spinal onset and slow progression patients. No correlation was demonstrated with cortisol. Increased hormonal levels in patients are probably due to hypothalamic-pituitary-adrenal axis activation. Nevertheless, in this preliminary report only PROG correlated positively with factors predicting better prognosis and survival. We hypothesize endogenous PROG and cortisol may be engaged in differential roles, the former possibly involved in a neuroprotective response. © 2010 John Wiley & Sons A/S.

  14. Environmental Pollution by Benzene and PM10 and Clinical Manifestations of Systemic Sclerosis: A Correlation Study.

    Science.gov (United States)

    Borghini, Alice; Poscia, Andrea; Bosello, Silvia; Teleman, Adele Anna; Bocci, Mario; Iodice, Lanfranco; Ferraccioli, Gianfranco; La Milìa, Daniele Ignazio; Moscato, Umberto

    2017-10-26

    Atmospheric air pollution has been associated with a range of adverse health effects. The environment plays a causative role in the development of Systemic Sclerosis (SSc). The aim of the present study is to explore the association between particulate (PM 10 ) and benzene (B) exposure in Italian patients with systemic sclerosis and their clinical characteristics of the disease. A correlation study was conducted by enrolling 88 patients who suffer from SSc at the Fondazione Policlinico "A. Gemelli" in Rome (Italy) in the period from January 2013 to January 2014. The average mean concentrations of B (in 11 monitoring sites) and PM 10 (in 14 sites) were calculated using data from the Regional Environmental Protection Agency's monitoring stations located throughout the Lazio region (Italy) and then correlated with the clinical characteristics of the SSc patients. Of the study sample, 92.5% were female. The mean age was 55 ± 12.9 years old and the mean disease duration from the onset of Raynaud's phenomenon was 13.0 ± 9.4 years. The Spearman's correlation showed that concentrations of B correlate directly with the skin score (R = 0.3; p ≤ 0.05) and inversely with Diffusing Lung Carbon Monoxide (DLCO) results (R = -0.36; p = 0.04). This study suggests a possible role of B in the development of diffuse skin disease and in a worse progression of the lung manifestations of SSc.

  15. Variants of ST8SIA1 are associated with risk of developing multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Seema Husain

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the central nervous system of unknown etiology with both genetic and environmental factors playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the major histocompatibility complex on chromosome 6p, is the strongest genetic risk factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have been identified as risk factors for MS with small effect. Here we present two independent studies supporting an allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1. The initial association was made in a single three-generation family where a single-nucleotide polymorphism (SNP rs4762896, was segregating together with HLA DR15/DQ6 in MS patients. A study of 274 family trios (affected child and both unaffected parents from Australia validated the association of ST8SIA1 in individuals with MS, showing transmission disequilibrium of the paternal alleles for three additional SNPs, namely rs704219, rs2041906, and rs1558793, with p = 0.001, p = 0.01 and p = 0.01 respectively. These findings implicate ST8SIA1 as a possible novel susceptibility gene for MS.

  16. Targeted assessment of lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Devine, Matthew S; Ballard, Emma; O'Rourke, Peter; Kiernan, Matthew C; Mccombe, Pamela A; Henderson, Robert D

    2016-01-01

    Estimating survival in amyotrophic lateral sclerosis (ALS) is challenging due to heterogeneity in clinical features of disease and a lack of suitable markers that predict survival. Our aim was to determine whether scoring of upper or lower motor neuron weakness is associated with survival. With this objective, 161 ALS subjects were recruited from two tertiary referral centres. Scoring of upper (UMN) and lower motor neuron (LMN) signs was performed, in addition to a brief questionnaire. Subjects were then followed until the censorship date. Univariate analysis was performed to identify variables associated with survival to either non-invasive ventilation (NIV) or death, which were then further characterized using Cox regression. Results showed that factors associated with reduced survival included older age, bulbar and respiratory involvement and shorter diagnostic delay (all p NIV or death (p ≤0.001) whereas UMN scores were poorly associated with survival. In conclusion, our results suggest that, early in disease assessment and in the context of other factors (age, bulbar, respiratory status), the burden of LMN weakness provides an accurate estimate of outcome. Such a scoring system could predict prognosis, and thereby aid in selection of patients for clinical trials.

  17. Matrix metalloproteinases: a review of their structure and role in systemic sclerosis.

    Science.gov (United States)

    Peng, Wen-jia; Yan, Jun-wei; Wan, Ya-nan; Wang, Bing-xiang; Tao, Jin-hui; Yang, Guo-jun; Pan, Hai-feng; Wang, Jing

    2012-12-01

    Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

  18. Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis.

    Science.gov (United States)

    Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik

    2017-06-01

    To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

  19. Plasma D-dimer concentration in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Montagnana Martina

    2006-01-01

    Full Text Available Abstract Background Systemic sclerosis (SSc is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. Methods To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. Results and discussion When compared to healthy controls, geometric mean and 95% confidence interval (IC95% of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361–363 ng/mL vs 229 ng/mL, IC95%: 228–231 ng/mL, p = 0.005. After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. Conclusion We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications.

  20. Serum osteopontin and vitronectin levels in systemic sclerosis.

    Science.gov (United States)

    Gundogdu, Baris; Yolbas, Servet; Yilmaz, Musa; Aydin, Suleyman; Koca, Sulayman Serdar

    2017-11-01

    Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a multifunctional glycoprotein. The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc). Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-β levels were analyzed. Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both). These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.

  1. Resource utilization in children with tuberous sclerosis complex and associated seizures: a retrospective chart review study.

    Science.gov (United States)

    Lennert, Barb; Farrelly, Eileen; Sacco, Patricia; Pira, Geraldine; Frost, Michael

    2013-04-01

    Seizures are a hallmark manifestation of tuberous sclerosis complex, yet data characterizing resource utilization are lacking. This retrospective chart review was performed to assess the economic burden of tuberous sclerosis complex with neurologic manifestations. Demographic and resource utilization data were collected for 95 patients for up to 5 years after tuberous sclerosis complex diagnosis. Mean age at diagnosis was 3.1 years, with complex partial and infantile spasms as the most common seizure types. In the first 5 years post-diagnosis, 83.2% required hospitalization, 30.5% underwent surgery, and the majority of patients (90.5%) underwent ≥3 testing procedures. In 79 patients with a full 5 years of data, hospitalizations, intensive care unit stays, diagnostic testing, and rehabilitation services decreased over the 5-year period. Resource utilization is cost-intensive in children with tuberous sclerosis complex and associated seizures during the first few years following diagnosis. Improving seizure control and reducing health care costs in this population remain unmet needs.

  2. Transcription factor Fos-Related Antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis

    OpenAIRE

    Maurer, B; Busch, N; Jüngel, A; Pileckyte, M; Gay, R E; Michel, B A; Schett, G; Gay, S; Distler, J; Distler, O

    2009-01-01

    BACKGROUND: -Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Methods and Results-Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endo...

  3. Corpora amylacea in temporal lobe epilepsy associated with hippocampal sclerosis

    Directory of Open Access Journals (Sweden)

    Ribeiro Marlise de Castro

    2003-01-01

    Full Text Available Hippocampal sclerosis (HS is the commonest pathology in epileptic patients undergoing temporal lobe epilepsy surgery. Beside, there are an increased density of corpora amylacea (CA founded in 6 to 63% of those cases. OBJECTIVE: verify the presence of CA and the clinical correlates of their occurrence in a consective series of patients undergoing temporal surgery with diagnosis of HS. METHOD: We reviewed 72 hippocampus specimens from January 1997 to July 2000. Student's t test for independent, samples, ANOVA and Tukey test were performed for statistical analysis. RESULTS: CA were found in 35 patients (49%, whose mean epilepsy duration (28.7 years was significantly longer than that group of patients without CA (19.5 years, p= 0.001. Besides, when CA were found, duration was also significantly correlated with distribution within hippocampus: 28.7 years with diffuse distribution of CA, 15.4 with exclusively subpial and 17.4 years with distribution subpial plus perivascular (p= 0.001. CONCLUSION: Our findings corroborate the presence of CA in patients with HS and suggest that a longer duration of epilepsy correlate with a more distribution of CA in hippocampus.

  4. Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease.

    Science.gov (United States)

    Caron, Melissa; Hoa, Sabrina; Hudson, Marie; Schwartzman, Kevin; Steele, Russell

    2018-06-30

    Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression ( i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD ( i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide ( D LCO ) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted D LCO Only five studies specifically aimed to validate the PFTs: two concluded that D LCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that D LCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression. Copyright ©ERS 2018.

  5. Acro-osteolysis as an indicator of severity in systemic sclerosis.

    Science.gov (United States)

    Arana-Ruiz, Juan Carlos; Amezcua-Guerra, Luis Manuel

    2016-01-01

    Systemic sclerosis is a rare disease that predominantly affects women. The Medsger severity scale has been used to assess the severity, but it requires expensive and poorly accessible studies and it does not include complications such acrosteolysis, calcinosis, pericardial disease or hypothyroidism that occur on a relatively frequent basis in this disease. There is no study that considers if comorbidities, such as primary biliary cirrhosis, are related to gravity. To determine the correlation between severity and the presence of such complications. 40 patients with systemic sclerosis, dividing them into tertiles according to severity were studied. Dichotomous variables were described using percentages, while dimensional by averages+SD. Statistical inference was performed using chi square test or Kruskal-Wallis test with Dunn post-test, as appropriate. A significance at P<.05 was set. Of all the complications studied there were only differences in severity with acrosteolysis. Within comorbidities, primary biliary cirrhosis is not associated with gravity. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  7. Screening for pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry

    2009-09-01

    Full Text Available The onset and progression of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc can be particularly aggressive; however, effective treatments are available. Therefore, early identification of patients with suspected PAH, confirmation of diagnosis, and intervention is essential. PAH may be challenging to diagnose in its earliest stages, particularly in populations that have multiple causes of breathlessness, and, therefore, screening is required. The optimal screening tools and methodology are, as yet, unknown, and this is confounded by a lack of consensus over which patients to screen. Current practice favours annual screening of all SSc patients using Doppler echocardiography to detect elevated right heart pressures. This will typically identify most patients with the various forms of pulmonary hypertension found in SSc. The optimum thresholds for Doppler echocardiography are still subject to investigation, especially for patients with mild pulmonary hypertension, and this technique may, therefore, yield a significant number of false-positives and a currently unknown number of false-negatives. Confirmatory right heart catheterisation remains necessary in all suspected cases. Further research is needed to identify the optimal tools and the screening approach with greatest specificity and selectivity.

  8. Evaluation and management of esophageal manifestations in systemic sclerosis.

    Science.gov (United States)

    Denaxas, Konstantinos; Ladas, Spyros D; Karamanolis, George P

    2018-01-01

    Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

  9. Penile involvement in Systemic Sclerosis: New Diagnostic and Therapeutic Aspects

    Directory of Open Access Journals (Sweden)

    Antonio Aversa

    2010-01-01

    Full Text Available Systemic Sclerosis (SSc is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ‘‘sclerodermic penis’’. Once-daily phosphodiesterase type-5 (PDE5 inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.

  10. Use of tocilizumab in systemic sclerosis: A brief literature review.

    Science.gov (United States)

    Fernández-Codina, A; Fernández-Fernández, J; Fernández-Pantiga, A

    2018-03-27

    The available treatments for systemic sclerosis (SS) have limited effectiveness. Treatment with tocilizumab (TCZ), a biological drug that inhibits interleukin 6 (IL-6), has recently been proposed. In this study, we conducted a literature review to assess the safety and efficacy of TCZ in SS. We found 52 articles, 10 of which we selected after evaluating the articles. In a randomised clinical trial, TCZ showed a nonsignificant improvement in the degree of skin induration, while another observational study showed neutral results. In this same clinical trial, the functional respiratory parameters showed a certain degree of stabilization. The safety profile of TCZ is acceptable; however, the current evidence regarding treatment of SS with TCZ is highly limited, although the drug could have a beneficial effect in skin disorder. New clinical trials are needed to determine the usefulness of TCZ in SS. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  11. Elephantiasis nostras verrucosa in a patient with systemic sclerosis.

    Science.gov (United States)

    Chatterjee, S; Karai, L J

    2009-12-01

    Elephantiasis nostras verrucosa (ENV) is an unusual skin condition characterized by dermal fibrosis and hyperkeratotic verrucous lesions resulting from chronic nonfilarial lymphoedema. The condition is similar to 'elephantiasis tropica', in which elephantiasis develops secondary to filariasis. Lymphatic obstruction can be primary or due to various causes such as surgery, tumour, radiation, congestive heart failure or obesity. Recurrent attacks of cellulitis lead to further impairment of lymphatic drainage, causing permanent swelling, dermal fibrosis and epidermal thickening. We report a case of a 56-year-old man with systemic sclerosis (SS), who presented with painful lesions on both legs, consistent with ENV. He developed extensive, fungating, papillomatous lesions on the skin of the legs, toes and dorsa of the feet over a period of 3 years. Histology revealed dense dermal fibrosis, oedema of the papillary dermis and extensive pseudo-epitheliomatous changes. To our knowledge, this is the first report of ENV in which SS was considered to be the primary cause for the impairment of lymphatic flow.

  12. Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

    Science.gov (United States)

    Marie, I; Antonietti, M; Houivet, E; Hachulla, E; Maunoury, V; Bienvenu, B; Viennot, S; Smail, A; Duhaut, P; Dupas, J-L; Dominique, S; Hatron, P-Y; Levesque, H; Benichou, J; Ducrotté, P

    2014-07-01

    To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions. © 2014 John Wiley & Sons Ltd.

  13. Esophageal hypomotility in systemic sclerosis. Close relationship with pulmonary involvement

    International Nuclear Information System (INIS)

    Kinuya, Keiko; Nakajima, Kenichi; Kinuya, Seigo; Michigishi, Takatoshi; Tonami, Norihisa; Takehara, Kazuhiko

    2001-01-01

    Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with extent of scleroderma, duration of disease, index of anti-topoisomerase I antibody (topo I), and pulmonary involvement. A multiple-swallow test was performed in 47 patients with SSc in the supine position with 99m Tc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p CO ) had higher RRs than those with normal %DL CO (40.5% vs. 19.6%; p=0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p<0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p<0.00005). Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis. (author)

  14. Esophageal hypomotility in systemic sclerosis. Close relationship with pulmonary involvement

    Energy Technology Data Exchange (ETDEWEB)

    Kinuya, Keiko [Tonami General Hospital, Toyama (Japan); Nakajima, Kenichi; Kinuya, Seigo; Michigishi, Takatoshi; Tonami, Norihisa; Takehara, Kazuhiko

    2001-04-01

    Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with extent of scleroderma, duration of disease, index of anti-topoisomerase I antibody (topo I), and pulmonary involvement. A multiple-swallow test was performed in 47 patients with SSc in the supine position with {sup 99m}Tc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p<0.05). There was no correlation between the RRs and the duration of disease. Patients with positive topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p<0.05). Patients with reduced % diffusion capacity for carbon monoxide (%DL{sub CO}) had higher RRs than those with normal %DL{sub CO} (40.5% vs. 19.6%; p=0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p<0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p<0.00005). Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis. (author)

  15. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  16. Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis.

    NARCIS (Netherlands)

    Minier, T.; Guiducci, S.; Bellando-Randone, S.; Bruni, C.; Lepri, G.; Czirjak, L.; Distler, O.; Walker, U.A.; Fransen, J.; Allanore, Y.; Denton, C.; Cutolo, M.; Tyndall, A.; Muller-Ladner, U.; Matucci-Cerinic, M.

    2014-01-01

    OBJECTIVES: The EULAR (European League Against Rheumatism) Scleroderma Trials and Research Group (EUSTAR) has identified preliminary criteria for very early diagnosis of systemic sclerosis (SSc). Our aim was to assess the prevalence of each proposed diagnostic item in a large observational patient

  17. Association of UV radiation with multiple sclerosis prevalence and sex ratio in France.

    Science.gov (United States)

    Orton, S-M; Wald, L; Confavreux, C; Vukusic, S; Krohn, J P; Ramagopalan, S V; Herrera, B M; Sadovnick, A D; Ebers, G C

    2011-02-01

    French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor. Mean annual and winter (December-March) UVB irradiation values were systematically compared to MS prevalence rates in corresponding regions of France. UVB data were obtained from the solar radiation database (SoDa) service and prevalence rates from previously published data on 2,667 MS cases registered with the national farmer health insurance system, Mutualité Sociale Agricole (MSA). Pearson correlation was used to examine the relationship of annual and winter UVB values with MS prevalence. Male and female prevalence were also analyzed separately. Linear regression was used to test for interaction of annual and winter UVB with sex in predicting MS prevalence. There was a strong association between MS prevalence and annual mean UVB irradiation (r = -0.80, p role for gender-specific effects of UVB exposure.

  18. Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

    2015-01-01

    Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for......-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.......Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used...... for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels...

  19. A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis

    DEFF Research Database (Denmark)

    Mechelli, Rosella; Umeton, Renato; Policano, Claudia

    2013-01-01

    of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge......, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate...... immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated...

  20. Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review.

    Science.gov (United States)

    Baptista, Rui; Serra, Sara; Martins, Rui; Teixeira, Rogério; Castro, Graça; Salvador, Maria João; Pereira da Silva, José António; Santos, Lèlita; Monteiro, Pedro; Pêgo, Mariano

    2016-07-02

    Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 ± 2.9 mmHg at rest and 43.0 ± 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP ≥40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate

  1. Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

    Science.gov (United States)

    Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

    2016-01-01

    Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  2. Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Coppedè, Fabio; Mancuso, Michelangelo; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Rocchi, Anna; Petrozzi, Lucia; Nesti, Claudia; Micheli, Dario; Bacci, Andrea; Migliore, Lucia; Murri, Luigi; Siciliano, Gabriele

    2007-06-13

    Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems. Particularly, increased levels of 8-oxoguanine and impairments of the DNA base excision repair system have been observed in neurons of ALS patients. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated with a reduced DNA repair activity. To evaluate the role of the hOGG1 Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136 patients and 129 matched controls. In the total population, we observed association between both the Cys326 allele (p=0.02) and the combined Ser326Cys+Cys326Cys genotype (OR=1.65, 95% CI=1.06-2.88) and increased risk of disease. After stratification by gender, the Cys326 allele (p=0.01), both the Ser326Cys genotype (OR=2.14, 95% CI=1.09-4.19) and the combined Ser326Cys+Cys326Cys genotype (OR=2.15, 95% CI=1.16-4.01) were associated with sALS risk only in males. No significant association between the Ser326Cys polymorphism and disease phenotype, including age and site of onset and disease progression, was observed. Present results suggest a possible involvement of the hOGG1 Ser326Cys polymorphism in sALS pathogenesis.

  3. Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

    Directory of Open Access Journals (Sweden)

    Audrey Dooley

    2012-01-01

    Full Text Available Systemic sclerosis (scleroderma: SSc is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO, a key mediator of oxidative stress, can profoundly influence the early microvasculopathy, and possibly the ensuing fibrogenic response. Animal models and human studies have also identified dietary antioxidants, such as epigallocatechin-3-gallate (EGCG, to function as a protective system against oxidative stress and fibrosis. Hence, targeting EGCG may prove a possible candidate for therapeutic treatment aimed at reducing both oxidant stress and the fibrotic effects associated with SSc.

  4. A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

    OpenAIRE

    van Hal, T. W.; van Bon, L.; Radstake, T. R. D. J.

    2011-01-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we pro...

  5. Multiple Sclerosis After Infectious Mononucleosis

    DEFF Research Database (Denmark)

    Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk

    2007-01-01

    BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis......, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish...... Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul...

  6. RARE CASE OF SYSTEMIC SCLEROSIS IN A CHILD AGED 4 MONTHS

    Directory of Open Access Journals (Sweden)

    S.S. Postnikov

    2007-01-01

    Full Text Available The article provides a clinical and morphologic description of a rare case of systemic sclerosis along with the beginning of the diseases during the infancy. In the clinical picture, the researchers identified occurrences of the systemic vasculitis: abundant cyanotic and red spotty rash with atrophy in the middle, thick edemas of legs and ankles, necrosis of the nail bone of the left little finger, banti's syndrome. In the histological picture, most characteristic peculiarities were: 3 stages of systemic sclerosis process development — inflammation, hardening and atrophy; disorganization of collagenous corium fibers; nidi of calcification along the borderline of corium and hypoderm; multiple ulcers of small and large intestines, perforation of one of which caused peritonitis and fatal outcome of the patient.Key words: infants, vasculitis, systemic sclerosis.

  7. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bruzzone, Santina, E-mail: santina.bruzzone@unige.it [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Battaglia, Florinda [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Mannino, Elena [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Parodi, Alessia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Fruscione, Floriana [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Basile, Giovanna [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Salis, Annalisa; Sturla, Laura [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Negrini, Simone; Kalli, Francesca; Stringara, Silvia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Filaci, Gilberto [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Department of Internal Medicine, Viale Benedetto XV 6, 16132 Genova (Italy); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer ABA is an endogenous hormone in humans, regulating different cell responses. Black-Right-Pointing-Pointer ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. Black-Right-Pointing-Pointer UV-B irradiation increases ABA content in SSc cultures. Black-Right-Pointing-Pointer SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-{beta} (TGF-{beta}). Conversely, migration toward ABA, but not toward TGF-{beta}, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.

  8. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

    International Nuclear Information System (INIS)

    Bruzzone, Santina; Battaglia, Florinda; Mannino, Elena; Parodi, Alessia; Fruscione, Floriana; Basile, Giovanna; Salis, Annalisa; Sturla, Laura; Negrini, Simone; Kalli, Francesca; Stringara, Silvia; Filaci, Gilberto

    2012-01-01

    Highlights: ► ABA is an endogenous hormone in humans, regulating different cell responses. ► ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. ► UV-B irradiation increases ABA content in SSc cultures. ► SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-β (TGF-β). Conversely, migration toward ABA, but not toward TGF-β, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.

  9. Hand and wrist involvement in systemic sclerosis: US features.

    Science.gov (United States)

    Freire, Véronique; Bazeli, Ramin; Elhai, Muriel; Campagna, Raphaël; Pessis, Éric; Avouac, Jérôme; Allanore, Yannick; Drapé, Jean-Luc; Guérini, Henri

    2013-12-01

    To characterize ultrasonographic (US) features in the hand of patients with systemic sclerosis (SSc) and to evaluate the sensitivity of US in the detection of calcinosis and acroosteolysis. The local ethics committee approved this study, and oral informed consent was obtained. A total of 44 consecutive patients with SSc (34 women; mean age, 56.1 years ± 12.1 [standard deviation]; 10 men; mean age, 45.0 years ± 14.0) and 30 healthy control subjects (20 women; mean age, 46.3 years ± 12.1; 10 men; mean age, 39.6 years ± 10.8) were included between October 2010 and December 2011. Bilateral US, including Doppler assessment of the wrists, hands, and fingers, was performed, and presence of synovitis, tenosynovitis with or without a layered appearance, calcifications, acroosteolysis, and distal vascularization was recorded. Radiography of both hands was performed to assess for acroosteolysis and calcinosis. Frequency of US features, sensitivity of US for calcinosis and acroosteolysis, and respective confidence intervals were calculated. Synovitis was found in 17 patients (39%). Tenosynovitis was found in 12 patients (27%), and it had a layered pattern in 15 (41%) of 37 cases. Calcinosis was found in 17 patients (39%) with US, with a sensitivity of 89%. Acroosteolysis was found in nine (20%) patients with US and in 10 (23%) patients with radiography, with 90% sensitivity for US. Distal vascularization was detected in 26 patients (59%) and 30 control subjects (100%) and was in contact with the acroosteolysis bed in seven (78%) of nine patients with SSc. US can be used to assess features of SSc, including synovitis, tenosynovitis, calcinosis, acroosteolysis, and distal vascularization and is sensitive for calcinosis and acroosteolysis detection. A layered pattern (similar to the appearance of an artichoke heart) of tenosynovitis was seen commonly. Online supplemental material is available for this article. © RSNA, 2013.

  10. Fertility and pregnancy outcome in women with systemic sclerosis.

    Science.gov (United States)

    Steen, V D; Medsger, T A

    1999-04-01

    To determine fertility and pregnancy outcome in women with systemic sclerosis (SSc; scleroderma) who had disease onset before age 45 years. All living women with scleroderma who had first been evaluated at the University of Pittsburgh Scleroderma Clinic after January 1, 1972 were sent a detailed self-administered questionnaire in 1986 specifically concerning pregnancy outcomes and infertility. This group was compared with 2 race- and age-matched control groups, one comprising women with rheumatoid arthritis (RA) and one comprising healthy neighborhood women identified by random-digit dialing. We determined the number, history, treatment, and outcome of women who either had never been pregnant or had attempted to become pregnant unsuccessfully for more than 1 year. We also obtained data regarding pregnancy outcomes, including the frequency of miscarriage, premature births, small full-term infants, perinatal deaths, and births of live healthy infants. The study group comprised 214 women with SSc, 167 with RA, and 105 neighborhood controls. There were no significant differences in the overall rates of miscarriage, premature births, small full-term births, or neonatal deaths between the 3 groups. Women with SSc were more likely than those without SSc to have adverse outcomes of pregnancy after the onset of their rheumatic disease, particularly premature births (also seen in RA women after disease onset) and small full-term infants. Although a significantly greater number of women with SSc had never been pregnant, there were no significant differences in the frequency of never having been pregnant or of infertility in the 3 groups after adjustment for contributing factors. This study indicates that women with SSc have acceptable pregnancy outcomes compared with those of women with other rheumatic disease and healthy neighborhood controls. Infertility was not a frequent problem. We believe that there are no excessive pregnancy risks to women with SSc or their infants

  11. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous

  12. Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J

    2010-11-01

    Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis

  13. Higher risk of complications in odynophagia-associated dysphagia in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Karen Fontes Luchesi

    2014-03-01

    Full Text Available Objective This investigation aimed to identify associated factors with dysphagia severity in amyotrophic lateral sclerosis (ALS. Method We performed a cross-sectional study of 49 patients with ALS. All patients underwent fiberoptic endoscopy evaluation of swallowing and answered a verbal questionnaire about swallowing complaints. The patients were divided into groups according to dysphagia severity. Results Among the factors analyzed, only odynophagia was associated with moderate or severe dysphagia. Conclusion Odynophagia was associated with moderate and severe dysphagia in ALS and suggests a high risk of pulmonary and nutritional complications.

  14. Human parvovirus B19 (B19V) infection in systemic sclerosis patients

    DEFF Research Database (Denmark)

    Zakrzewska, K.; Corcioli, F.; Carlsen, Karen Marie

    2009-01-01

    BACKGROUND: Our previous reports suggested a possible association between parvovirus B19 (B19V) infection and systemic sclerosis (SSc), based on higher prevalence of B19V DNA in SSc patients in respect to controls. METHODS: In the present study, to further evaluate the differences in the pattern...... of B19 infection in SSc, skin biopsies and bone marrow samples from patients and controls were analysed for B19V DNA detection, genotyping and viral expression. RESULTS: B19V DNA was detected in skin biopsies from 39/49 SSc patients and from 20/28 controls. Bone marrow showed positive in 17/29 SSc...... in the skin of genotype 1-positive patients and not in control skins. CONCLUSION: The results outline some differences in the rate of persistence of B19V DNA, in the simultaneous persistence of 2 genotypes and in the pattern of viral expression among SSc patients and controls Udgivelsesdato: 2009...

  15. Retinoic acid for treatment of systemic sclerosis and morphea: A literature review.

    Science.gov (United States)

    Thomas, Renee M; Worswick, Scott; Aleshin, Maria

    2017-03-01

    Systemic sclerosis and morphea are connective tissue diseases characterized by tightening, thickening, and hardening of the skin, leading to significant morbidity. Unfortunately, current treatment options have limited efficacy for many patients. Cutaneous manifestations of these diseases arise from excess collagen deposition and fibrosis in the skin, through pathogenic mechanisms which have yet to be extensively detailed at the causal immune and cellular levels. Research elucidating the mechanism of action of retinoic acid on collagen production in the skin and case series highlighting the success of retinoic acid on the skin manifestations of systemic sclerosis and on morphea demonstrate its promise as a treatment. Herein they will briefly review the treatment options for both systemic sclerosis and morphea, and will discuss the potential of retinoic acid as a therapy and the supporting evidence from the literature, highlighting the previously published basic science and clinical studies investigating the role of retinoic acid in the treatment of sclerotic skin diseases. © 2016 Wiley Periodicals, Inc.

  16. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate) : a phase 2, randomised, controlled trial

    NARCIS (Netherlands)

    Khanna, Dinesh; Denton, Christopher P.; Jahreis, Angelika; van Laar, Jacob M.; Frech, Tracy M.; Anderson, Marina E.; Baron, Murray; Chung, Lorinda; Fierlbeck, Gerhard; Lakshminarayanan, Santhanam; Allanore, Yannick; Pope, Janet E.; Riemekasten, Gabriela; Steen, Virginia; Müller-Ladner, Ulf; Lafyatis, Robert; Stifano, Giuseppina; Spotswood, Helen; Chen-Harris, Haiyin; Dziadek, Sebastian; Morimoto, Alyssa; Sornasse, Thierry; Siegel, Jeffrey; Furst, Daniel E.

    2016-01-01

    Background Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis. Methods We did this double-blind,

  17. Associations between proprioceptive neural pathway structural connectivity and balance in people with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Brett W Fling

    2014-10-01

    Full Text Available Mobility and balance impairments are a hallmark of multiple sclerosis (MS, affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to 1 map the cortical proprioceptive pathway in-vivo using diffusion weighted imaging and 2 assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls. Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere’s proprioceptive pathway was significantly correlated with overall balance performance in healthy controls, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon 1 cerebellar-regulated proprioceptive control, 2 the vestibular system, and/or 3 the visual system.

  18. Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis

    DEFF Research Database (Denmark)

    Iversen, Line V; Ullman, Susanne; Østergaard, Ole

    2015-01-01

    BACKGROUND: Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ invol...

  19. Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Bălănescu, Paul; Lădaru, Anca; Bălănescu, Eugenia; Băicuş, Cristian; Dan, Gheorghe Andrei

    2014-08-01

    Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. Medline and Embase databases were searched in February 2014. Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

  20. A Case with Systemic Sclerosis Following Exposure To Silica and Vibration

    Directory of Open Access Journals (Sweden)

    Aslı Ürkmez

    2012-06-01

    Full Text Available Systemic sclerosis is an autoimmune disease characterized by inflammatory, vascular and sclerotic changes in the internal organs. Although the etiology is not known with certainty; silica dust, which is one of the environmental risk factors, can lead to scleroderma by some immunological changes. In this case, a mine worker, who worked in a mercury mine during a 15-year period, developed systemic sclerosis due to exposure to chronic silica and vibration, is presented. (Turk J Dermatol 2012; 6: 45-7

  1. Balloon cells associated with granule cell dispersion in the dentate gyrus in hippocampal sclerosis.

    Science.gov (United States)

    Thom, M; Martinian, L; Caboclo, L O; McEvoy, A W; Sisodiya, S M

    2008-06-01

    Granule cell dispersion (GCD) is a common finding in hippocampal sclerosis in patients with intractable focal epilepsy. It is considered to be an acquired, post-developmental rather than a pre-existing abnormality, involving dispersion of either mature or newborn neurones, but the precise factors regulating it and its relationship to seizures are unknown. We present two cases of GCD with associated CD34-immunopositive balloon cells, a cell phenotype associated with focal cortical dysplasia type IIB, considered to be a developmental cortical lesion promoting epilepsy. This observation opens up the debate regarding the origin of balloon cells and CD34 expression and their temporal relationship to seizures.

  2. A wireless body measurement system to study fatigue in multiple sclerosis

    NARCIS (Netherlands)

    Yu, F.; Bilberg, A.; Stenager, E.; Rabotti, C.; Zhang, B.; Mischi, M.

    2012-01-01

    Fatigue is reported as the most common symptom by patients with multiple sclerosis (MS). The physiological and functional parameters related to fatigue in MS patients are currently not well established. A new wearable wireless body measurement system, named Fatigue Monitoring System (FAMOS), was

  3. Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Kishore Malyavantham

    Full Text Available To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC, relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression.The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS, 128 secondary progressive MS (SP-MS, 33 primary progressive MS (PP-MS and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed.The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b, respectively. Antibodies against CSF114(Glc, KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies.Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.

  4. Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis.

    Science.gov (United States)

    Braun-Moscovici, Yolanda; Furst, Daniel E; Markovits, Doron; Rozin, Alexander; Clements, Philip J; Nahir, Abraham Menahem; Balbir-Gurman, Alexandra

    2008-11-01

    .Sclerodactyly with acroosteolysis (AO) and calcinosis are prominent features of systemic sclerosis (SSc), but the pathogenesis of these findings is poorly understood. Vitamin D and parathyroid hormone (PTH) have a crucial role in bone metabolism and resorption and may affect AO and calcinosis. We assessed vitamin D and PTH in patients with SSc. Medical records of 134 consecutive patients with SSc (American College of Rheumatology criteria) followed at the rheumatology department during the years 2003-2006 were reviewed for clinical assessment, laboratory evaluation [including 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, PTH, creatinine, and albumin]; imaging data confirming AO and/or calcinosis. Patients followed routinely at least once a year were included (81 patients). Of these, 60 patients' medical records were found to have complete, relevant clinical, laboratory, and radiographic imaging. Thirteen patients had diffuse disease and 47 limited disease - 51 women and 9 men, 44 Jews and 16 Arabs; mean age 55 +/- 14 years; disease duration 8 +/- 6 years. AO with or without calcinosis was observed in 42 patients (70%). Vitamin D deficiency was found in 46% of patients (16 out of 44 Jewish patients, 10 out of 16 Arab patients). PTH was elevated in 21.7% of patients. Significant correlations were observed between acroosteolysis and PTH (p = 0.015), calcinosis (p = 0.009), and disease duration (p = 0.008), and between PTH and vitamin D levels (p = 0.01). All patients had normal serum concentrations of calcium, phosphorus, magnesium, and albumin, and liver and kidney functions. In this group of Mediterranean patients with SSc, the incidence of vitamin D deficiency and secondary hyperparathyroidism was surprisingly high. This finding correlated with the occurrence of AO and calcinosis. Low levels of vitamin D may reflect silent malabsorption and might be a risk factor for secondary hyperparathyroidism and bone resorption. Traditional dress habits and low

  5. Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

    Science.gov (United States)

    Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

    2011-04-01

    Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

  6. Central nervous system involvement in primary Sjogren`s syndrome manifesting as multiple sclerosis.

    Science.gov (United States)

    Liu, Jing-Yao; Zhao, Teng; Zhou, Chun-Kui

    2014-04-01

    Central nervous system symptoms in patients with primary Sjogren`s syndrome are rare. They can present as extraglandular manifestations and require a differential diagnosis from multiple sclerosis. Due to a variety of presentations, Sjogren`s syndrome with neurologic involvement may be difficult to diagnose. Here, we report a case of a 75-year-old woman who was first diagnosed with multiple sclerosis in 2010, but who was subsequently diagnosed with primary Sjogren`s syndrome 2 years later after showing signs of atypical neurologic manifestations. Therefore, primary Sjogren`s syndrome should be suspected in patients who present with atypical clinical and radiologic neurologic manifestations.

  7. Light therapy for multiple sclerosis-associated fatigue: Study protocol for a randomized controlled trial.

    Science.gov (United States)

    Mateen, Farrah J; Manalo, Natalie C; Grundy, Sara J; Houghton, Melissa A; Hotan, Gladia C; Erickson, Hans; Videnovic, Aleksandar

    2017-09-01

    Fatigue is the most commonly reported symptom among multiple sclerosis (MS) patients, more than a quarter of whom consider fatigue to be their most disabling symptom. However, there are few effective treatment options for fatigue. We aim to investigate whether supplemental exposure to bright white light will reduce MS-associated fatigue. Eligible participants will have clinically confirmed multiple sclerosis based on the revised McDonald criteria (2010) and a score ≥36 on the Fatigue Severity Scale (FSS). Participants will be randomized 1:1 to bright white light (10,000 lux; active condition) or dim red light (treatment period, and a 4-week washout period. Participants will record their sleep duration, exercise, caffeine, and medication intake daily. Participants will record their fatigue using the Visual Analogue Fatigue Scale (VAFS) 4 times every third day, providing snapshots of their fatigue level at different times of day. Participants will self-report their fatigue severity using FSS on 3 separate visits: at baseline (week 0), following completion of the treatment phase (week 6), and at study completion (week 10). The primary outcome will be the change in the average FSS score after light therapy. We will perform an intention-to-treat analysis, comparing the active and control groups to assess the postintervention difference in fatigue levels reported on FSS. Secondary outcome measures include change in global VAFS scores during the light therapy and self-reported quality of life in the Multiple Sclerosis Quality of Life-54. We present a study design and rationale for randomizing a nonpharmacological intervention for MS-associated fatigue, using bright light therapy. The study limitations relate to the logistical issues of a self-administered intervention requiring frequent participant self-report in a relapsing condition. Ultimately, light therapy for the treatment of MS-associated fatigue may provide a low-cost, noninvasive, self-administered treatment

  8. [User Associations and Multiple Sclerosis: Impact of Neoliberalism in France on the trajectory of life].

    Science.gov (United States)

    Colinet, Séverine

    Multiple sclerosis is a neurological disease that induces limitation of bodily performance. It has a major impact on the work and social life of affected persons because the patient's disability, often in the absence of visible symptoms, is o source of incomprehension in a society marked by the neoliberal dogma of performance. Patient associations often provide support for patients in their trajectory. The aim of this research was to identify how the principles of neoliberalism manifest themselves in the discourse of multiple sclerosis subjects, to understand the effects of neoliberal integration, and to clarify the role played by the association involvement in the trajectories of life. This qualitative study was based on 30 individual interviews and 4 group interviews with patients, as well as 23 observations of patient group meetings and focus groups. Ten people met in interviews also kept a mini-diary, in order to record their daily involvement in a patient association. Data were analysed thematically, initially independently then by cross-linked AtlasTi software. The association constitutes two forms, practical and ideological, an illustration of the resistance to neoliberalism, particularly in the form of individual and collective responsibilities. However, to a certain extent, it also recreates performance spaces. From a practical point of view, this research re-affirms the need to create collective activities to accompany people with chronic illness.

  9. Association of Aortic Valve Sclerosis with Previous Coronary Artery Disease and Risk Factors

    Directory of Open Access Journals (Sweden)

    Filipe Carvalho Marmelo

    2014-11-01

    Full Text Available Background: Aortic valve sclerosis (AVS is characterized by increased thickness, calcification and stiffness of the aortic leaflets without fusion of the commissures. Several studies show an association between AVS and presence of coronary artery disease. Objective: The aim of this study is to investigate the association between presence of AVS with occurrence of previous coronary artery disease and classical risk factors. Methods: The sample was composed of 2,493 individuals who underwent transthoracic echocardiography between August 2011 and December 2012. The mean age of the cohort was 67.5 ± 15.9 years, and 50.7% were female. Results: The most frequent clinical indication for Doppler echocardiography was the presence of stroke (28.8%, and the most common risk factor was hypertension (60.8%. The most prevalent pathological findings on Doppler echocardiography were mitral valve sclerosis (37.1% and AVS (36.7%. There was a statistically significant association between AVS with hypertension (p < 0.001, myocardial infarction (p = 0.007, diabetes (p = 0.006 and compromised left ventricular systolic function (p < 0.001. Conclusion: Patients with AVS have higher prevalences of hypertension, stroke, hypercholesterolemia, myocardial infarction, diabetes and compromised left ventricular systolic function when compared with patients without AVS. We conclude that there is an association between presence of AVS with previous coronary artery disease and classical risk factors.

  10. The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis

    International Nuclear Information System (INIS)

    Kahan, A.; Devaux, J.Y.; Amor, B.; Menkes, C.J.; Weber, S.; Venot, A.; Strauch, G.

    1990-01-01

    In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long-term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (+/- SD) number of segments with thallium 201 myocardial perfusion defects (6.5 +/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment with captopril; p less than 0.02) and increased the mean global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/- 2.1 after captopril; p less than 0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease

  11. Metallothionein expression in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Ortega-Aznar, A

    2003-01-01

    Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS...

  12. Molecular and cellular profiling of systemic sclerosis and its preclinical stages

    NARCIS (Netherlands)

    Cossu, Marta

    2017-01-01

    The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is preceded by vascular and immune modifications. On the basis of SSc-specific autoantibodies and nailfold capillary lesions it is possible to

  13. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Tani, M; Jensen, J

    1999-01-01

    Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether...

  14. Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

    NARCIS (Netherlands)

    Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.J.M. de; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and

  15. Influence of TYK2 in systemic sclerosis susceptibility : a new locus in the IL-12 pathway

    NARCIS (Netherlands)

    López-Isac, Elena; Campillo-Davo, Diana; Bossini-Castillo, Lara; Guerra, Sandra G; Assassi, Shervin; Simeón, Carmen Pilar; Carreira, Patricia; Ortego-Centeno, Norberto; García de la Peña, Paloma; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg Hw; Voskuyl, Alexandre E; de Vries-Bouwstra, Jeska; Herrick, Ariane; Worthington, Jane; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy Rdj; Mayes, Maureen D; Martín, Javier

    OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus

  16. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    NARCIS (Netherlands)

    Rueda, B.; Broen, J.; Simeon, C.; Hesselstrand, R.; Diaz, B.; Suarez, H.; Ortego-Centeno, N.; Riemekasten, G.; Fonollosa, V.; Vonk, M.C.; Hoogen, F.H.J. van den; Sanchez-Roman, J.; Aguirre-Zamorano, M.A.; Garcia-Portales, R.; Pros, A.; Camps, M.T.; Gonzalez-Gay, M.A.; Coenen, M.J.H.; Airo, P.; Beretta, L.; Scorza, R.; Laar, J. van; Gonzalez-Escribano, M.F.; Nelson, J.L.; Radstake, T.R.D.J.; Martin, J.

    2009-01-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy

  17. [Management of symptoms associated with spasticity in patients with multiple sclerosis].

    Science.gov (United States)

    Fernández-Pablos, María Asunción; Costa-Frossard, Lucienne; García-Hernández, Carlos; García-Montes, Inmaculada; Escutia-Roig, Matilde

    To describe the role of nurses in the management of symptoms related to spasticity in patients with multiple sclerosis (MS). A descriptive study was developed based on a questionnaire on spasticity in MS patients. The questionnarie was completed through an anonymous tele-voting system at a national meeting with nurses involved in the management of these patients. Apart from fatigue, according to the opinion of the participants, the spasticity symptom associated with MS most notified by patients was difficulty in walking, followed by spasms and pain. Participants thought that it is important that nursing takes: 1) a role in identifying these symptoms, 2) should focus on the detection of the triggering or aggravating factors, and 3) on providing support in the assessment of the level of spasticity. It is important to inform about the correct use of anti-spasticity drugs, how to adjust the dosage and side effects of treatments, including cannabinoids via an oromucosal spray, titrating its doses according to each patient, and monitoring its tolerability, efficacy and adherence. Although there are usually resources to follow up these patients, there are still important gaps, including the lack of a specific follow-up protocol. Although all the participants are experts in the management of patients with MS, there is still diversity in the functions they perform, and the available resources they have in their hospitals. Nurses act as a key element in the process of identification of symptoms, training and monitoring of these patients with spasticity in EM. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. The role of nailfold capillary dropout on mortality in systemic sclerosis.

    Science.gov (United States)

    Tieu, Joanna; Hakendorf, Paul; Woodman, Richard J; Patterson, Karen; Walker, Jenny; Roberts-Thomson, Peter

    2018-05-01

    Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P dropout scores (log-rank χ 2 = 8.75, P = 0.003) and antibody status (log-rank χ 2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P dropout attenuated the impact of autoantibody group on survival. Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality. © 2018 Royal Australasian College of Physicians.

  19. STAT4 is a genetic risk factor for systemic sclerosis in a Chinese population.

    Science.gov (United States)

    Yi, L; Wang, J C; Guo, X J; Gu, Y H; Tu, W Z; Guo, G; Yang, L; Xiao, R; Yu, L; Mayes, M D; Assassi, S; Jin, L; Zou, H J; Zhou, X D

    2013-01-01

    Systemic sclerosis (SSc) is an immune-mediated and complex genetic disease. An association of single-nucleotide polymorphisms (SNPs) in the STAT4 gene with SSc has been reported in European Caucasians, North Americans and Japanese. We undertook the current study to examine whether the STAT4 SNPs are also associated with susceptibility to SSc and SSc subsets in a Han Chinese population. A total of 453 Han Chinese patients with SSc and 534 healthy controls were examined in the study. The SNPs rs7574865, rs10168266 and rs3821236 of the STAT4 gene were examined with SNP TaqMan assays. The T-allele carriers of rs7574865 and rs10168266 were strongly associated with the presence of anti-topoisomerase I (ATA) and pulmonary fibrosis in SSc patients, as well as with diffuse cutaneous SSc (dcSSc). The presence of anti-centromere (ACA) and limited cutaneous SSc (lcSSc) did not show significant association with any of the examined SNPs. The results were consistent with previous reports in other ethnic populations in supporting the notion that polymorphisms of STAT4 may play an important role in susceptibility to SSc. It also revealed different genetic aspects of SSc subsets in a Han Chinese population.

  20. Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis

    NARCIS (Netherlands)

    Smolders, J; Peelen, Evelyn; Thewissen, Mariëlle; Menheere, Paul; Damoiseaux, Jan; Hupperts, Raymond

    BACKGROUND: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). OBJECTIVES: The purpose of this study was to explore whether there is an association between MS and DBP. METHODS: We compared DBP

  1. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  2. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R.; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H. P.; Koppers, Max; Blokhuis, Anna M.; Sproviero, William; Jones, Ashley R.; Kenna, Kevin P.; van Eijk, Kristel R.; Harschnitz, Oliver; Schellevis, Raymond D.; Brands, William J.; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A.; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, A. Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W.; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M.; van der Kooi, Anneke J.; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; del Bo, Roberto; Comi, Giacomo P.; D'alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P.; Fifita, Jennifer A.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Grosskreutz, Julian; Witte, Otto W.; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A.; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Franke, Lude; Pers, Tune H.; Brown, Robert H.; Glass, Jonathan D.; Landers, John E.; Hardiman, Orla; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R.; Visscher, Peter M.; de Bakker, Paul I. W.; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan H.

    2016-01-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  3. Substantial adverse association of visual and vascular comorbidities on visual disability in multiple sclerosis.

    Science.gov (United States)

    Marrie, Ruth Ann; Cutter, Gary; Tyry, Tuula

    2011-12-01

    Visual comorbidities are common in multiple sclerosis (MS) but the impact of visual comorbidities on visual disability is unknown. We assessed the impact of visual and vascular comorbidities on severity of visual disability in MS. In 2006, we queried participants of the North American Research Committee on Multiple Sclerosis (NARCOMS) about cataracts, glaucoma, uveitis, hypertension, hypercholesterolemia, heart disease, diabetes and peripheral vascular disease. We assessed visual disability using the Vision subscale of Performance Scales. Using Cox regression, we investigated whether visual or vascular comorbidities affected the time between MS symptom onset and the development of mild, moderate and severe visual disability. Of 8983 respondents, 1415 (15.9%) reported a visual comorbidity while 4745 (52.8%) reported a vascular comorbidity. The median (interquartile range) visual score was 1 (0-2). In a multivariable Cox model the risk of mild visual disability was higher among participants with vascular (hazard ratio [HR] 1.45; 95% confidence interval [CI]: 1.39-1.51) and visual comorbidities (HR 1.47; 95% CI: 1.37-1.59). Vascular and visual comorbidities were similarly associated with increased risks of moderate and severe visual disability. Visual and vascular comorbidities are associated with progression of visual disability in MS. Clinicians hearing reports of worsening visual symptoms in MS patients should consider visual comorbidities as contributing factors. Further study of these issues using objective, systematic neuro-ophthalmologic evaluations is warranted.

  4. Multiple sclerosis and employment: Associations of psychological factors and work instability.

    Science.gov (United States)

    Wicks, Charlotte Rose; Ward, Karl; Stroud, Amanda; Tennant, Alan; Ford, Helen L

    2016-10-12

    People with multiple sclerosis often stop working earlier than expected. Psychological factors may have an impact on job retention. Investigation may inform interventions to help people stay in work. To investigate the associations between psychological factors and work instability in people with multiple sclerosis. A multi-method, 2-phased study. Focus groups were held to identify key themes. Questionnaire packs using validated scales of the key themes were completed at baseline and at 8-month follow-up. Four key psychological themes emerged. Out of 208 study subjects 57.2% reported medium/high risk of job loss, with marginal changes at 8 months. Some psychological variables fluctuated significantly, e.g. depression fell from 24.6% to 14.5%. Work instability and anxiety and depression were strongly correlated (χ2 p work instability, and baseline depression levels also predicted later work instability (Hosmer-Lemeshow test 0.899; Nagelkerke R Square 0.579). Psychological factors fluctuated over the 8-month follow-up period. Some psychological variables, including anxiety and depression, were significantly associated with, and predictive of, work instability. Longitudinal analysis should further identify how these psychological attributes impact on work instability and potential job loss in the longer term.

  5. Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database.

    Science.gov (United States)

    Ingegnoli, Francesca; Ardoino, Ilaria; Boracchi, Patrizia; Cutolo, Maurizio

    2013-09-01

    The aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. Data collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. 62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The "early" and "active" scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the "late" scleroderma pattern was found more frequently in the more severe forms of the disease. These data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases

    Directory of Open Access Journals (Sweden)

    Asako Otomo

    2012-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a heterogeneous group of incurable motor neuron diseases (MNDs characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative genes for ALS/MNDs have been identified and their underlying pathogenesis, including oxidative stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction, neural inflammation, protein misfolding and accumulation, dysfunctional intracellular trafficking, abnormal RNA processing, and noncell-autonomous damage, has begun to emerge. It is currently believed that a complex interplay of multiple toxicity pathways is implicated in disease onset and progression. Among such mechanisms, ones that are associated with disturbances of protein homeostasis, the ubiquitin-proteasome system and autophagy, have recently been highlighted. Although it remains to be determined whether disease-associated protein aggregates have a toxic or protective role in the pathogenesis, the formation of them results from the imbalance between generation and degradation of misfolded proteins within neuronal cells. In this paper, we focus on the autophagy-lysosomal and endocytic degradation systems and implication of their dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway could be a major target for the development of therapeutic agents for ALS/MNDs.

  7. New insights into the gene expression associated to amyotrophic lateral sclerosis.

    Science.gov (United States)

    Recabarren-Leiva, Daniela; Alarcón, Marcelo

    2018-01-15

    Amyotrophic lateral sclerosis (ALS) is the most prevalent neuromuscular disease worldwide. It is a lethal and progressive neurodegenerative disease, principally affecting motor neurons; patient clinical characteristics are muscle weakness, dysphagia and respiratory failure. The mean age is related to family history (40years, familial ALS or FALS) or with no family history (50years), but it is more common in people aged 60-69years. The cause of ALS is not known and it is not known yet why it affects some people and not others. However expert consensus is that molecular alterations in different cells are involved in the development and progression of the disease. For example, motor neuron death is caused by a variety of cellular defects, including the processing of RNA molecules, water channels, and calcium levels, increasing evidence that these alterations of cells in the nervous system play an important role in ALS. Here we will systematically examine different genes (AQP1, SLC14A1, MT1X, DSCR1L1, PCP4, UCHL1, GABRA1, EGR1, OLFM1 and VSNL1) that are "up or down" regulated in the motor cortex and spinal cord and their association with ALS risk. These could be novel biomarkers associated with ALS risk. We built an interaction Network with Cytoscape, this was used to identify pathways, miRNA and drugs associated to ALS. The most important affected pathway is PI3K-Akt signaling. Thirteen microRNAs (miRNA-19B1, miRNA-107, miRNA-124-1, miRNA-124-2, miRNA-9-2, miRNA-29A, miRNA-9-3, miRNA-328, miRNA-19B2, miRNA-29B2, miRNA-124-3, miRNA-15A and miRNA-9-1) and four drugs (Estradiol, Acetaminophen, Progesterone and resveratrol) for new possible treatments were identified. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Serum Endoglin Levels in Patients Suffering from Systemic Sclerosis and Elevated Systolic Pulmonary Arterial Pressure

    Directory of Open Access Journals (Sweden)

    Paola Ximena Coral-Alvarado

    2010-01-01

    Full Text Available Background. Pulmonary arterial hypertension (PAH is the main cause of morbimortality in systemic sclerosis (SSc. Increased Eng expression has been demonstrated in SSc patients. Objective. Ascertaining serum levels of Eng in SSc patients with and without elevated systolic pulmonary arterial pressure (sPAP and comparing them with that of healthy volunteers. Methods. A cross-sectional study was carried out. A commercial ELISA kit was used for measuring serum concentrations of Eng in 60 subjects: 40 patients with SSc with and without elevated sPAP, compared to 20 healthy control subjects. Elevated sPAP was detected by echocardiogram. Results. No association between positive Eng and elevated sPAP was found when compared to the SSc without elevated sPAP group (OR=2.85; 0.65–12.88 95% CI; P=.11; however, an association was found between positive Eng and elevated sPAP compared to healthy controls (OR=23.22; 2.46–1050.33 95% CI; P=.001, and weak association was found between the positive Eng with SSc without elevated sPAP group compared to healthy controls (OR=8.14, 0.8–393.74 95% CI; P=.046. Conclusion. Raised serum levels of Eng in SSc patients compared to healthy controls were found, suggesting a role for Eng in SSc vasculopathy and not just in elevated sPAP. However, prospective studies are needed to verify such observations.

  9. Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

    Science.gov (United States)

    Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

    2015-01-01

    Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid

  10. Recovery from severe dysphagia in systemic sclerosis - myositis ...

    African Journals Online (AJOL)

    Background: Dysphagia is common in inflammatory myopathies and usually responds to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic gastrostomy is associated with significant morbidity and high mortality. Clinical case: A 56-year old African Black woman initially presented with systemic ...

  11. The circulating cell-free microrna profile in systemic sclerosis is distinct from both healthy controls and Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Steen, S. O.; Iversen, L. V.; Carlsen, A. L.

    2015-01-01

    Objective. To evaluate the expression profile of cell-free circulating microRNA (miRNA) in systemic sclerosis (SSc), healthy controls (HC), and systemic lupus erythematosus (SLE). Methods. Total RNA was purified from plasma and 45 different, mature miRNA were measured using quantitative PCR assays...

  12. Reversible Pulmonary Arterial Hypertension Associated with Interferon-Beta Treatment for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    E Gibbons

    2015-01-01

    Full Text Available Interferon (IFN therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH, and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months.

  13. International Differences in Multiple Sclerosis Health Outcomes and Associated Factors in a Cross-sectional Survey

    Directory of Open Access Journals (Sweden)

    Grace D. Reilly

    2017-05-01

    Full Text Available Multiple sclerosis (MS is a major cause of disability and poor quality of life (QOL. Previous studies have shown differences in MS health outcomes between countries. This study aimed to examine the associations between international regions and health outcomes in people with MS. Self-reported data were taken from the Health Outcomes and Lifestyle In a Sample of people with Multiple Sclerosis online survey collected in 2012. The 2,401 participants from 37 countries were categorized into three regions: Australasia, Europe, and North America. Differences were observed between regions in disability, physical and mental health QOL, fatigue, and depression, but most of these disappeared after adjusting for sociodemographic, disease, and lifestyle factors in multivariable regression models. However, adjusted odds for disability were higher in Europe [odds ratio (OR: 2.17, 95% confidence interval (CI: 1.28 to 3.67] and North America (OR: 1.79, 95% CI: 1.28 to 2.51 compared to Australasia. There may be other unmeasured factors that vary between regions, including differences in access and quality of healthcare services, determining disability in MS. When assessing differences in MS health outcomes, lifestyle factors and medication use should be taken into consideration.

  14. Small calcified lesions suggestive of neurocysticercosis are associated with mesial temporal sclerosis

    Directory of Open Access Journals (Sweden)

    Marcos C. B. Oliveira

    2014-07-01

    Full Text Available Recent studies have suggested a possible relationship between temporal lobe epilepsy with mesial temporal sclerosis (MTS and neurocysticercosis (NC. We performed a case-control study to evaluate the association of NC and MTS. Method: We randomly selected patients with different epilepsy types, including: MTS, primary generalized epilepsy (PGE and focal symptomatic epilepsy (FSE. Patients underwent a structured interview, followed by head computed tomography (CT. A neuroradiologist evaluated the scan for presence of calcified lesions suggestive of NC. CT results were matched with patients’ data. Results: More patients in the MTS group displayed calcified lesions suggestive of NC than patients in the other groups (p=0.002. On multivariate analysis, MTS was found to be an independent predictor of one or more calcified NC lesions (p=0.033. Conclusion: After controlling for confounding factors, we found an independent association between NC calcified lesions and MTS.

  15. Cardiac transplant in young female patient diagnosed with diffuse systemic sclerosis.

    Science.gov (United States)

    Bennasar, Guillermo; Carlevaris, Leandro; Secco, Anastasia; Romanini, Felix; Mamani, Marta

    2016-01-01

    Systemic sclerosis (SS) in a multifactorial and systemic, chronic, autoimmune disease that affects the connective tissue. We present this clinical case given the low prevalence of diffuse SS with early and progressive cardiac compromise in a young patient, and treatment with cardiac transplantation. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

    2001-01-01

    Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis. Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5...

  17. Nailfold capillaroscopy abnormalities as predictors of mortality in patients with systemic sclerosis.

    Science.gov (United States)

    Kayser, Cristiane; Sekiyama, Juliana Y; Próspero, Lucas C; Camargo, Cintia Z; Andrade, Luis E C

    2013-01-01

    Peripheral microangiopathy is a hallmark of systemic sclerosis (SSc) and can be early detected by nailfold capillaroscopy (NFC). This study aimed to examine whether more severe peripheral microangiopathy at NFC are predictive factor for death in SSc patients. 135 SSc patients who performed NFC between June 2001 and July 2009 were included. The following NFC parameters were evaluated: number of capillary loops/mm, avascular score (scored from 0 to 3), and number of enlarged and giant capillary loops. Univariate and multivariate regression models were used to analyse the association of mortality with NFC and clinical parameters. At the time of the analysis (August 2010), 123 patients were alive, and 12 were dead. By univariate analysis, male gender, forced vital capacity 1.5 on NFC were associated with a significantly increase risk of death. By multivariate analysis, an avascular score >1.5 was the only independent predictor of death (hazard ratio 2.265). Survival rates from diagnosis at 1, 5 and 10 years were lower in patients with avascular score >1.5 (97%, 86%, and 59%, respectively) compared with those with avascular score ≤1.5 (97%, 97%, and 91% respectively) (p=0.009 by log rank test). Avascular scores higher than 1.5 at NFC was an independent predictor of death in SSc, suggesting that NFC can be useful for predicting SSc outcome.

  18. Dipyridamole thallium imaging for detecting cardiac involvement in patients with systemic sclerosis (scleroderma)

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Yoshio; Matsubara, Noboru; Tani, Akihiro; Morozumi, Takakazu; Hori, Masatsugu; Kitabatake, Akira; Kamada, Takenobu; Kimura, Kazufumi; Kozuka, Takahiro (Osaka Univ. (Japan). Faculty of Medicine)

    1990-02-01

    Dipyridamole thallium-201 imaging was carried out in 21 patients with progressive systemic sclerosis (PSS) to assess its value in detecting impaired myocardium and coronary microcirculation associated with PSS. Depending upon the degree of cardiac function, the patients were classified as having either ejection fraction of 50% or more (Group I, n=17) or less than 50% (Group II, n=4). In Group I, four patients had transient defect in which perfusion defects were seen on early images but not seen on delayed images; three had reverse redistribution in which defects were not seen on early images but seen on delayed images; and three had persistent defects which were seen on both early and delayed images. A decreased washout of thallium-201 was seen in 9 patients. In an analysis of both perfusion defects and washout rate, 13 patients (76%) in Group I were found to have abnormal findings. This suggests that disturbed coronary microcirculation or impaired myocardium may frequently develop even when EF is normal. All of the patients categorized as having a decreased cardiac function (Group II) had perfusion defect, suggesting the presence of myocardial fibrosis. In PSS, deterioration of cardiac function seemed to be associated with progression of myocardial fibrosis. Dipyridamole thallium imaging may be a sensitive method for detecting cardiac lesions in PSS. It also has the potential for detecting decreased coronary flow reserve or slightly impaired myocardium even without decreased EF. (N.K.).

  19. Transcriptional Activity of Nuclear Factor κB Family Genes in Patients with Systemic Sclerosis.

    Science.gov (United States)

    Lis-Święty, Anna; Gola, Joanna; Mazurek, Urszula; Brzezińska-Wcisło, Ligia

    2017-05-01

    Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology and unclear pathogenesis. Evaluation of the activation of nuclear factor κB (NF-κB) family genes IκBα, p50, p52, p65, and c-Rel, potentially involved in the regulation of immunity, inflammation, angiogenesis, and tissue remodeling in SSc, was carried out. The study included 19 patients with limited SSc, 11 patients with early SSc, and 10 healthy persons constituting the control group. Real-time QRT-PCR was used to evaluate the mRNAs in peripheral blood samples. The patients with early SSc showed a decrease in transcriptional activity of IκBα inhibitor and c-Rel subunit. Transcriptional activity decrease in the other patients with limited SSc included genes encoding c-Rel and p50, subunits of NF-κB factor. Deregulation of intracellular signal transduction by NF-κB takes place at the beginning of SSc and in its fibrosis stage. Associations between clinical variables and NF-κB related gene expression as well as the activation of NF-κB family members in SSc patients should be addressed in future studies. © 2017 by the Association of Clinical Scientists, Inc.

  20. Neuropathic pain in Systemic Sclerosis patients: A cross-sectional study.

    Science.gov (United States)

    Sousa-Neves, Joana; Cerqueira, Marcos; Santos-Faria, Daniela; Afonso, Carmo; Teixeira, Filipa

    2018-01-31

    To investigate if patients with Systemic Sclerosis (SSc) show a higher prevalence of neuropathic pain (NP) in comparison with controls. To study the relationship between clinical variables of the disease and NP among SSc patients. 48 patients and 45 controls were included. Presence of NP was assessed applying the DN4 "Douleur Neuropathique en 4 Questions" questionnaire. Different clinical variables were also assessed in patients. Statistical analysis included parametric, nonparametric tests and multivariate logistic regression. NP was significantly higher in SSc patients (56.2% vs 13.3%, p<0.001). Mean Modified Rodnan Skin Score was independently associated with the presence of NP (p<0.05, OR 1.90). Peripheral nervous system involvement in SSc is not well studied and, as far as the authors are aware, this is the first study published evaluating NP in SSc patients and controls. These findings should raise the awareness of the clinician to recognize and address the presence of NP in these patients, especially in those with severe skin involvement. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  1. Pressure and pain In Systemic sclerosis/Scleroderma - an evaluation of a simple intervention (PISCES: randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Alcacer-Pitarch Begonya

    2012-02-01

    Full Text Available Abstract Background Foot problems associated with Systemic Sclerosis (SSc/Scleroderma have been reported to be both common and disabling. There are only limited data describing specifically, the mechanical changes occurring in the foot in SSc. A pilot project conducted in preparation for this trial confirmed the previous reports of foot related impairment and reduced foot function in people with SSc and demonstrated a link to mechanical etiologies. To-date there have been no formal studies of interventions directed at the foot problems experienced by people with Systemic Sclerosis. The primary aim of this trial is to evaluate whether foot pain and foot-related health status in people with Systemic Sclerosis can be improved through the provision of a simple pressure-relieving insole. Methods The proposed trial is a pragmatic, multicenter, randomised controlled clinical trial following a completed pilot study. In four participating centres, 140 consenting patients with SSc and plantar foot pain will be randomised to receive either a commercially available pressure relieving and thermally insulating insole, or a sham insole with no cushioning or thermal properties. The primary end point is a reduction in pain measured using the Foot Function Index Pain subscale, 12 weeks after the start of intervention. Participants will complete the primary outcome measure (Foot Function Index pain sub-scale prior to randomisation and at 12 weeks post randomisation. Secondary outcomes include participant reported pain and disability as derived from the Manchester Foot Pain and Disability Questionnaire and plantar pressures with and without the insoles in situ. Discussion This trial protocol proposes a rigorous and potentially significant evaluation of a simple and readily provided therapeutic approach which, if effective, could be of a great benefit for this group of patients. Trial registration number ISRCTN: ISRCTN02824122

  2. No evidence of association between optic neuritis and secondary LHON mtDNA mutations in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Andalib, Sasan; Talebi, Mahnaz; Sakhinia, Ebrahim

    2017-01-01

    Leber's Hereditary Optic Neuropathy (LHON) shares features with Multiple Sclerosis (MS). Both diseases develop optic lesions. Frequent secondary LHON mutations in MS patients may explain the optic damage. Here, we tested the hypothesis that secondary LHON mutations are associated with optic...

  3. Association between DPP6 polymorphism and the risk of progressive multiple sclerosis in Northern and Southern Europeans

    DEFF Research Database (Denmark)

    Brambilla, Paola; Esposito, Federica; Lindstrom, Eva

    2012-01-01

    In this study, we investigated the role of the dipeptidyl-peptidase-6 (DPP6) gene in the etiopathogenesis of progressive forms of multiple sclerosis (PrMS). This gene emerged as a candidate gene in a genome-wide association study (GWAS) performed in an Italian sample of PrMS and controls in which...

  4. Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

    Directory of Open Access Journals (Sweden)

    Hanysova Sandra

    2017-08-01

    Full Text Available Objective: The aim of our study was to determine the relation of particular genetic variants in selected genes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1; rs10735781 EVI5 to the risk of multiple sclerosis (MS development and find out the possible association with disease disability progression rate. Material and methods: Our study included 202 MS patients and 174 healthy control volunteers. MS patients were divided according to disability progression rate to three groups - slowly progressing, mid-rate progressing and rapidly progressing. All DNA samples were isolated from venous blood. Genotyping was performed by PCR-RFLP and multiplex PCR. Results: Our analysis showed that GSTT1 null genotype (OR 0.56; 95%CI 0.33 -0.95; p=0.04 and GSTM1, GSTT1 double null genotype (OR 0.32; 95%CI 0.14 - 0.74; p=0.006 are potentially protective in relation to MS. We observed similar result in GSTT1 null genotype in association with mid-rate progression (OR 0.48; 95%CI 0.24 - 0.97; p=0.05. Frequency of GSTM1 and GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (OR 0.22; 95%CI 0.05 - 0.98; p=0.05 and middle (OR 0.33; 95%CI 0.11 - 0.99; p=0.045. We did not show any significant association of genetic changes rs1695 in GSTP1 and rs10735781 in EVI5 with MS or rate of disease progression. Conclusions: Genetic basis of multiple sclerosis is still not fully elucidated. Further research may clarify our results and confirm the value of studied factors for clinical practice.

  5. Separate Influences of Birth Order and Gravidity/Parity on the Development of Systemic Sclerosis

    Science.gov (United States)

    COCKRILL, TONYA; del JUNCO, DEBORAH J.; ARNETT, FRANK C.; ASSASSI, SHERVIN; TAN, FILEMON K.; McNEARNEY, TERRY; FISCHBACH, MICHAEL; PERRY, MARILYN; MAYES, MAUREEN D.

    2010-01-01

    Objective Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Methods Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Results Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06–1.50 for birth order 2–5; OR 2.22, 95% CI 1.57–3.15 for birth order 6–9; and OR 3.53, 95% CI 1.68–7.45 for birth order 10–15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Conclusion Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility. PMID:20391489

  6. Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis

    Science.gov (United States)

    Carmona, F David; Gutala, Ramana; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Vicente-Rabaneda, Esther; García-Hernández, Francisco J; de la Peña, Paloma García; Fernández-Castro, Mónica; Martínez-Estupiñán, Lina; Egurbide, María Victoria; Tsao, Betty P; Gourh, Pravitt; Agarwal, Sandeep K; Assassi, Shervin; Mayes, Maureen D; Arnett, Frank C; Tan, Filemon K; Martín, Javier

    2012-01-01

    Objective Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features. Methods Two case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc. Results Four out of five analysed SNPs were Significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: pFDR=6.14 × 10−4, OR=0.78; rs4963128: pFDR=6.14 × 10−4, OR=0.79; rs702966: pFDR=3.83 × 10−3, OR=0.82; and rs2246614: pFDR=3.83 × 10−3, OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant. Conclusions The results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases. PMID:21926187

  7. Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.

    Science.gov (United States)

    Cockrill, Tonya; del Junco, Deborah J; Arnett, Frank C; Assassi, Shervin; Tan, Filemon K; McNearney, Terry; Fischbach, Michael; Perry, Marilyn; Mayes, Maureen D

    2010-03-01

    Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06-1.50 for birth order 2-5; OR 2.22, 95% CI 1.57-3.15 for birth order 6-9; and OR 3.53, 95% CI 1.68-7.45 for birth order 10-15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.

  8. Nailfold Capillaroscopy - Its Role in Diagnosis and Differential Diagnosis of Microvascular Damage in Systemic Sclerosis.

    Science.gov (United States)

    Lambova, Sevdalina; Hermann, W; Muller-Ladner, Ulf

    2013-01-01

    In the nailfold area, specific diagnostic microvascular abnormalities are easily recognized via capillaroscopic examination in systemic sclerosis (SSc). They are termed "scleroderma" type capillaroscopic pattern, which includes presence of dilated, giant capillaries, haemorrhages, avascular areas, and neoangiogenic capillaries and are observed in the majority of SSc patients (in more than 90%). LeRoy and Medsger (2001) proposed criteria for early diagnosis of SSc with inclusion of the abnormal capillaroscopic changes and suggested to prediagnose SSc prior to the development of other manifestations of the disease. It is a new era in the diagnosis of SSc. At present, an international multicenter project is performed. It aims validation of criteria for very early diagnosis of SSc (project VEDOSS (Very Early Diagnosis of Systemic Sclerosis) and is organized by European League Against Rheumatism (EULAR) Scleroderma Trials and Reasearch. Very recently the first results of the VEDOSS project were processed and new EULAR/ACR (American College of Rheumatology) classification criteria have been validated and published (2013), in which the characteristic capillaroscopic changes have been included. Our observations confirm the high frequency of the specific capillaroscopic changes of the fingers in SSc, which have been found in 97.2% of the cases from the studied patient population. We have performed for the first time capillaroscopic examinations of the toes in SSc. Interestingly,"scleroderma type" capillaroscopic pattern was also found at the toes in a high proportion of patients - 66.7%, but it is significantly less frequent as compared with fingers (97.2%, p<0.05). In our opinion, the examination of the toes of SSc patients should be considered as it suggests an additional opportunity for evaluation of the microvascular changes in these patients although the observed changes are in a lower proportion of cases. Thus, capillaroscopic examination is a cornerstone for the very

  9. Ventilation distribution and small airway function in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    B.R.A. Silva

    2017-05-01

    Full Text Available Background: Despite the importance of traditional pulmonary function tests (PFTs in managing systemic sclerosis (SSc, many patients with pulmonary disease diagnosed by computed tomography (CT present with normal PFTs. Objective: To evaluate the efficacy of the nitrogen single-breath washout (N2SBW test in diagnosing SSc and to correlate N2SBW parameters with the PFT indexes used in the follow-up of these patients, clinical data, and CT findings. Methods: Cross-sectional study in which 52 consecutive SSc patients were subjected to spirometry, body plethysmography, analysis of the diffusing capacity for carbon monoxide (DLCO, analysis of respiratory muscle strength, N2SBW testing, and CT analysis. Results: Twenty-eight patients had a forced vital capacity (FVC that was 120% of the predicted value, while 15 patients had a closing volume/vital capacity (CV/VC that was >120% of the predicted value. A significant difference in Phase III slopeN2SBW was observed when the patients with predominant traction bronchiectasis and honeycombing were compared to the patients with other CT patterns (p < 0.0001. The Phase III slopeN2SBW was correlated with FVC (rs = −0.845, p < 0.0001 and DLCO (rs = −0.600, p < 0.0001, and the CV/VC was correlated with FVC (rs = −0.460, p = 0.0006 and residual volume/total lung capacity (rs = 0.328, p = 0.017. Conclusion: Ventilation heterogeneity is a frequent finding in SSc patients that is associated with restrictive damage, changes in pulmonary diffusion, and CT patterns. In addition, approximately one-third of the patients presented with findings that were compatible with small airway disease. Keywords: Systemic sclerosis, Respiratory function tests, Nitrogen single-breath washout test

  10. [Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension].

    Science.gov (United States)

    Navarro, Carmen

    2006-11-01

    Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension Lung disease is present in most of the patients with systemic sclerosis and is now the most important cause of mortality. Interstitial lung disease and pulmonary hypertension are, so far, the main disorders found and both are difficult to detect at the earliest stages. However, diagnostic tools such as immunological test, lung function test, high resolution CT, bronchoalveolar lavage, echocardiography, right-side cardiac catheterization, or lung biopsy are necessary to accurately evaluate the clinical status and allow to improve the management organ-specific ad hoc. Progress in immunological and vascular therapies as well as other emergence drugs offer new expectations to scleroderma patients. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

  11. Association study between XRCC1 gene polymorphisms and sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Coppedè, Fabio; Migheli, Francesca; Lo Gerfo, Annalisa; Fabbrizi, Maria Rita; Carlesi, Cecilia; Mancuso, Michelangelo; Corti, Stefania; Mezzina, Nicoletta; del Bo, Roberto; Comi, Giacomo P; Siciliano, Gabriele; Migliore, Lucia

    2010-01-01

    The aim of the present study was to investigate the possible contribution of three common functional polymorphisms in the DNA repair protein X-ray repair cross-complementing group 1 (XRCC1), namely Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487), to sporadic amyotrophic lateral sclerosis (SALS). We genotyped 206 Italian SALS patients and 203 matched controls for XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms by means of PCR/RFLP technique, searching for association between any of the studied polymorphisms and disease risk, age and site of onset. We observed a statistically significant difference in XRCC1 Gln399 allele frequencies between SALS cases and controls (0.39/0.28; p=0.001). The present study suggests that the XRCC1 Arg399Gln polymorphism might contribute to SALS risk.

  12. Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

    Science.gov (United States)

    Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

    2004-01-01

    Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

  13. No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study

    NARCIS (Netherlands)

    Wattjes, M.P.; van Oosten, B.W.; de Graaf, W.L.; Seewann, A.M.; Bot, J.C.J.; van den Berg, R.; Uitdehaag, B.M.J.; Polman, C.H.; Barkhof, F.

    2011-01-01

    Background: Recent studies using colour-coded Doppler sonography showed that chronic impaired venous drainage from the central nervous system is almost exclusively found in multiple sclerosis (MS) patients. This study aimed to investigate the intracranial and extracranial venous anatomy and the

  14. No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study

    NARCIS (Netherlands)

    Wattjes, Mike P.; van Oosten, Bob W.; de Graaf, Wolter L.; Seewann, Alexandra; Bot, Joseph C. J.; van den Berg, René; Uitdehaag, Bernard M. J.; Polman, Chris H.; Barkhof, Frederik

    2011-01-01

    Recent studies using colour-coded Doppler sonography showed that chronic impaired venous drainage from the central nervous system is almost exclusively found in multiple sclerosis (MS) patients. This study aimed to investigate the intracranial and extracranial venous anatomy and the intracerebral

  15. Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options

    Directory of Open Access Journals (Sweden)

    Wang S

    2014-10-01

    Full Text Available Shelly Wang,1 Aria Fallah2,3 1Department of Neurosurgery, University of Toronto, Toronto, ON, Canada; 2Department of Neurosurgery, Miami Children’s Hospital, Miami, FL, USA; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Abstract: Seizures are clinically significant manifestations associated with 79%–90% of patients with tuberous sclerosis complex. Often occurring within the first year of life in the form of infantile spasms, seizures interfere with neuropsychiatric, social, and cognitive development and carry significant individual and societal consequences. Prompt identification and treatment of seizures is an important focus in the overall management of tuberous sclerosis complex patients. Medical management, either after seizure onset or prophylactically in infants with electroencephalographic abnormalities, is considered first-line therapy. Vigabatrin and adrenocorticotropic hormone have emerged over the past few decades as mainstay pharmacologic modalities. Furthermore, emerging research on mammalian target of rapamycin inhibitors demonstrated promise for the management of seizures and subependymal giant cell astrocytoma. For appropriate surgical candidates with an epileptogenic zone associated with one or more glioneuronal hamartomas, ideally in noneloquent cortex, resective surgery can be considered, which provides a cure in 56% of patients. For medically refractory patients who do not meet criteria for curative surgery, palliative surgical approaches focused on reducing seizure burden, in the form of corpus callosotomy and vagus nerve stimulation, are alternative management options. Lastly, the ketogenic diet, a reemerging therapy based on the anticonvulsant effects of ketone bodies, can be utilized independently or in conjunction with other treatment modalities for the management of difficult-to-treat seizures. Keywords: epilepsy, adrenocorticotropic hormone, vigabatrin, mammalian

  16. /sup 131/I albumin study of patients carrying progressive systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cossermelli, W; Carvalho, N; Papaleo Netto, M [Sao Paulo Univ. (Brazil). Centro de Medicina Nuclear

    1974-05-01

    /sup 131/I albumin metabolic changes were studied in 14 female patients with progressive systemic sclerosis. A statistical study of the gathered data disclosed increased distribution and turnover half-life and diminished turnover rate of radioactive substance. Since T/2 of turnover and turnover rate are the result produced by the albumin synthesis and degradation, they are probably lowered during active disease causing hypoalbuminemia. The aminoacids also are probably absorbed by other protein like the gammaglobuline synthesis.

  17. Evaluation of quatitative scintigraphic method in diagnosis of esophagic involvement of Progressive Systemic Sclerosis

    International Nuclear Information System (INIS)

    Von Muehlen, C.A.

    1985-01-01

    Twenty patients with Progressive Systemic Sclerosis are studied by scintigraphic methodology. The esophageal transit method is used for liquid and solid meals. The results are compared with the ones of a control group, without or not gastrintestinal problems but without autoimmune diasese. 99 sup(m)Tc-sulfurcolloid is used as labelling compound. The studies were done in supine and orthostatical position. (M.A.C.) [pt

  18. A system out of breath: how hypoxia possibly contributes to the pathogenesis of systemic sclerosis.

    Science.gov (United States)

    van Hal, T W; van Bon, L; Radstake, T R D J

    2011-01-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients.

  19. A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    T. W. van Hal

    2011-01-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients.

  20. Prevalence and clinical significance of cathepsin G antibodies in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    M. Favaro

    2011-09-01

    Full Text Available Objectives: To evaluate the prevalence and clinical significance of cathepsin G antibodies in patients affected with systemic sclerosis (SSc, scleroderma. Methods: 115 patients affected by SSc, 55 (47,8% with diffuse scleroderma (dSSc and 60 (52,2% with limited scleroderma (lSSc, were tested for cathepsin G antibodies by ELISA method. Moreover these sera were evaluated by indirect immunofluorescence (IIF on ethanol and formalin fixed human neutrophils. Results: By means of the ELISA method 16 (13,9% patients were found to be sera positive for anti-cathepsin G, 2 (12.5% of which showed a perinuclear fluorescence pattern (P-ANCA and 4 (25% an atypical ANCA staining, while 10 (62,5% were negative on IIF. The IIF on scleroderma sera revealed 5 (4,3% P-ANCA and 18 (15,7% atypical ANCA patterns. The anti-cathepsin G antibodies significantly prevailed in scleroderma sera (p=0.02 when their frequency was compared with that of healthy controls; while they were not significantly associated to any clinical or serological features of SSc patients. Conclusions: The anti-cathepsin G antibodies were significantly frequent in scleroderma sera; however, no clinical correlations were found. Thus, the significance of their presence in SSc still needs to be clarified.

  1. Features of systemic sclerosis-rheumatoid arthritis overlap syndrome (SS-RA overlap syndrome

    Directory of Open Access Journals (Sweden)

    O. V. Desinova

    2007-01-01

    Full Text Available Objective. To reveal clinico-laboratory, immunologic and immunogenetic features of systemic sclerosis-rheumatoid arthritis overlap syndrome (SS-RA.Material and methods. 32 pts with SS-RA (1 male, 31 female aged 22 to 74 years with disease onset at 18 to 69 years and disease duration from 1 to 35 years were included. Complex laboratory and instrumental examination was performed including nailfold capillaroscopy. A part of pts was also evaluated with magnetic resonance imaging of hands. Serum level of rheumatoid factor, antinuclear factor, circulating immune complexes, C-reactive protein, antibodies to cyclic citrullinated peptide (ACCP was evaluated. Genotyping of DRB1 alleles was performed.Results. Characteristic features of SS-RA were prevalence of limited skin damage, less prominent peripheral and visceral symptoms of SS, presence of anti-topoisomerase antibodies and erosive arthritis, high laboratory and immunological activity, more frequent association with DRB1*01.Conclusion. SS-RA possesses its own clinical features and can be considered as a distinct subtype of SS.

  2. Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis.

    Science.gov (United States)

    Bhakuni, Darshan S; Vasdev, Vivek; Garg, M K; Narayanan, Krishanan; Jain, Rahul; Mullick, Gautam

    2012-02-01

    Nailfold capillaroscopy (NFC) is a simple, non-invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement. Twenty-two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30× and 100× magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature. The capillary density was significantly less in all cases of SSc as compared to controls (5.3 ± 1.4 vs. 8.7 ± 1.2; P Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

  3. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers.

    Science.gov (United States)

    Barnes, Jammie; Mayes, Maureen D

    2012-03-01

    To identify the recent data regarding prevalence, incidence, survival, and risk factors for systemic sclerosis (SSc) and to compare these data to previously published findings. SSc disease occurrence data are now available for Argentina, Taiwan, and India and continue to show wide variation across geographic regions. The survival rate is negatively impacted by older age of onset, male sex, scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer, and antitopoisomerase and anti-U1 antibodies. It appears that silica exposure confers an increased risk for developing scleroderma, but this exposure accounts for a very small proportion of male patients. Smoking is not associated with increased SSc susceptibility. Malignancies are reported in scleroderma at an increased rate, but the magnitude of this risk and the type of cancer vary among reports. Prevalence and incidence of SSc appears to be greater in populations of European ancestry and lower in Asian groups. Exposure to silica dust appears to be an environmental trigger, but this only accounts for a small proportion of male cases. Evidence for increased risk of neoplasia is suggestive, but the magnitude of the risk and the types of malignancies vary among reports.

  4. Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report.

    Science.gov (United States)

    Chinniah, Keith J; Mody, Girish M

    2017-06-01

    Dysphagia is common in inflammatory myopathies and usually responds to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic gastrostomy is associated with significant morbidity and high mortality. A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years later she had a myositis flare with severe dysphagia. Her myositis improved after high doses of corticosteroids, azathioprine and two doses of intravenous immunoglobulin (IVIG). As her dysphagia persisted, she was fed via a percutaneous endoscopic gastrostomy (PEG) tube and given a course of rituximab. Her dysphagia gradually resolved and the PEG tube was removed within two months. She received another dose of rituximab six months later and continued low dose prednisone and azathioprine. Her muscle power improved, weight returned to normal and she remained well 20 months after hospital discharge. Our patient with SSC-myositis overlap and severe dysphagia requiring PEG feeding, improved with high dose corticosteroids, azathioprine, two courses of IVIG and rituximab, and remained in remission 20 months after hospital discharge.

  5. The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

    Science.gov (United States)

    Pauling, John D

    2018-05-01

    The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.

  6. Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland.

    Science.gov (United States)

    Herrick, Ariane L; Ennis, Holly; Bhushan, Monica; Silman, Alan J; Baildam, Eileen M

    2010-02-01

    Childhood scleroderma encompasses a rare, poorly understood spectrum of conditions. Our aim was to ascertain the incidence of childhood scleroderma in its different forms in the UK and Ireland, and to describe the age, sex, and ethnicity of the cases. The members of 5 specialist medical associations including pediatricians, dermatologists, and rheumatologists were asked to report all cases of abnormal skin thickening suspected to be localized (including linear) scleroderma or systemic sclerosis (SSc) in children scleroderma and 7 (7%) with SSc. This gave an incidence rate per million children per year of 3.4 (95% confidence interval [95% CI] 2.7-4.1) for localized scleroderma, including an incidence rate of 2.5 (95% CI 1.8-3.1) for linear scleroderma, and 0.27 (95% CI 0.1-0.5) for SSc. Of the 87 localized cases, 62 (71%) had linear disease. Of localized disease cases, 55 (63%) were female, 71 (82%) were classified as white British, and the patients' mean age when first seen in secondary care was 10.4 years. Of the 7 SSc cases, all were female, 6 (86%) were white British, and the mean age when first seen was 12.1 years. The median delay between onset and being first seen was 13.1 months for localized scleroderma and 7.2 months for SSc. These data provide additional estimates of the incidence of this rare disorder and its subforms.

  7. Clinical and laboratory features of systemic sclerosis complicated with localized scleroderma.

    Science.gov (United States)

    Toki, Sayaka; Motegi, Sei-ichiro; Yamada, Kazuya; Uchiyama, Akihiko; Kanai, Sahori; Yamanaka, Masayoshi; Ishikawa, Osamu

    2015-03-01

    Localized scleroderma (LSc) primarily affects skin, whereas systemic sclerosis (SSc) affects skin and various internal organs. LSc and SSc are considered to be basically different diseases, and there is no transition between them. However, LSc and SSc have several common characteristics, including endothelial cell dysfunction, immune activation, and excess fibrosis of the skin, and there exist several SSc cases complicated with LSc during the course of SSc. Clinical and laboratory characteristics of SSc patients with LSc remain unclear. We investigated the clinical and laboratory features of 8 SSc patients with LSc among 220 SSc patients (3.6%). The types of LSc included plaque (5/8), guttate (2/8), and linear type (1/8). All cases were diagnosed as having SSc within 5 years before or after the appearance of LSc. In three cases of SSc with LSc (37.5%), LSc skin lesions preceded clinical symptoms of SSc. Young age, negative antinuclear antibody, and positive anti-RNA polymerase III antibody were significantly prevalent in SSc patients with LSc. The positivity of anticentromere antibody tended to be prevalent in SSc patients without LSc. No significant difference in the frequency of complications, such as interstitial lung disease, reflux esophagitis, and pulmonary artery hypertension, was observed. The awareness of these characteristic of SSc with LSc are essential to establish an early diagnosis and treatment. © 2015 Japanese Dermatological Association.

  8. [Multiple sclerosis management system 3D. Moving from documentation towards management of patients].

    Science.gov (United States)

    Schultheiss, T; Kempcke, R; Kratzsch, F; Eulitz, M; Pette, M; Reichmann, H; Ziemssen, T

    2012-04-01

    The increasing therapeutic options for relapsing-remitting multiple sclerosis require a specific treatment and risk management to recognize the individual response as well as potential side effects. To switch from pure MS documentation to MS management by implementing a new multiple sclerosis management and documentation tool may be of importance. This article presents the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). MSDS 3D allows documentation and visualization of visit schedules and mandatory examinations via defined study modules by integration of data input from patients, attending physicians and MS nurses. It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information is collected via interactive touch screens. A specific module which is part of MSDS 3D's current version allows the monthly monitoring of patients under treatment with natalizumab. A checklist covering clinical signs of progressive multifocal leukoencephalopathy (PML) and a detailed questionnaire about the handling of natalizumab in practice have additionally been added. The MS patient management system MSDS 3D has successfully been implemented and is currently being evaluated in a multi-centre setting. Advanced assessment of patient data may allow improvements in clinical practice and research work. The addition of a checklist and a questionnaire into the natalizumab module may support the recognition of PML during its early, treatable course.

  9. Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90.

    Science.gov (United States)

    Nazari, Banafsheh; Rice, Lisa M; Stifano, Giuseppina; Barron, Alexander M S; Wang, Yu Mei; Korndorf, Tess; Lee, Jungeun; Bhawan, Jag; Lafyatis, Robert; Browning, Jeffrey L

    2016-10-01

    Tissue injury triggers the activation and differentiation of multiple cell types to minimize damage and initiate repair processes. In systemic sclerosis, these repair processes appear to run unchecked, leading to aberrant remodeling and fibrosis of the skin and multiple internal organs, yet the fundamental pathological defect remains unknown. We describe herein a transition wherein the abundant CD34(+) dermal fibroblasts present in healthy human skin disappear in the skin of systemic sclerosis patients, and CD34(-), podoplanin(+), and CD90(+) fibroblasts appear. This transition is limited to the upper dermis in several inflammatory skin diseases, yet in systemic sclerosis, it can occur in all regions of the dermis. In vitro, primary dermal fibroblasts readily express podoplanin in response to the inflammatory stimuli tumor necrosis factor and IL-1β. Furthermore, we show that on acute skin injury in both human and murine settings, this transition occurs quickly, consistent with a response to inflammatory signaling. Transitioned fibroblasts partially resemble the cells that form the reticular networks in organized lymphoid tissues, potentially linking two areas of fibroblast research. These results allow for the visualization and quantification of a basic stage of fibroblast differentiation in inflammatory and fibrotic diseases in the skin. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Proton spectroscopy study of the masseter in patients with systemic sclerosis

    International Nuclear Information System (INIS)

    Marcucci, Marcelo; Abdala, Nitamar

    2009-01-01

    Objective: To evaluate metabolite concentration in the masseter of patients with systemic sclerosis, by analyzing creatine, choline, lipid and lactate levels, and correlating them with the presence of mandibular osteolysis. Materials and methods: The sample included 25 individuals, 15 of them with diagnosis of systemic sclerosis, divided into two groups according to the presence (group I) or absence (group II) of osteolysis, and 10 healthy individuals (group III, control). All of them were submitted to proton magnetic resonance spectroscopy with PRESS sequence and 3D acquisition. Results: Metabolite analysis showed that the creatine and lipid levels were the same for the three groups. Patients in group I presented higher levels of choline when compared with group III. On the other hand, lower lactate levels were observed in groups I and II when compared with the healthy individuals. Creatine/lipid and choline/lactate ratios were the same in the three groups. Conclusion: Lower lactate levels were observed in the patients with systemic sclerosis (groups I and II). Choline levels were increased in the patients with mandibular osteolysis (group I). Creatine/choline, lipid/lactate and choline/lipid ratios were different among the three groups. Further studies are necessary to understand the role played by the masseter in the development of mandibular osteolysis. (author)

  11. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    Science.gov (United States)

    Rueda, B; Broen, J; Simeon, C; Hesselstrand, R; Diaz, B; Suárez, H; Ortego-Centeno, N; Riemekasten, G; Fonollosa, V; Vonk, M C; van den Hoogen, F H J; Sanchez-Román, J; Aguirre-Zamorano, M A; García-Portales, R; Pros, A; Camps, M T; Gonzalez-Gay, M A; Coenen, M J H; Airo, P; Beretta, L; Scorza, R; van Laar, J; Gonzalez-Escribano, M F; Nelson, J L; Radstake, T R D J; Martin, J

    2009-06-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.

  12. Climatic factors associated with amyotrophic lateral sclerosis: a spatial analysis from Taiwan.

    Science.gov (United States)

    Tsai, Ching-Piao; Tzu-Chi Lee, Charles

    2013-11-01

    Few studies have assessed the spatial association of amyotrophic lateral sclerosis (ALS) incidence in the world. The aim of this study was to identify the association of climatic factors and ALS incidence in Taiwan. A total of 1,434 subjects with the primary diagnosis of ALS between years 1997 and 2008 were identified in the national health insurance research database. The diagnosis was also verified by the national health insurance programme, which had issued and providing them with "serious disabling disease (SDD) certificates". Local indicators of spatial association were employed to investigate spatial clustering of age-standardised incidence ratios in the townships of the study area. Spatial regression was utilised to reveal any association of annual average climatic factors and ALS incidence for the 12-year study period. The climatic factors included the annual average time of sunlight exposure, average temperature, maximum temperature, minimum temperature, atmospheric pressure, rainfall, relative humidity and wind speed with spatial autocorrelation controlled. Significant correlations were only found for exposure to sunlight and rainfall and it was similar in both genders. The annual average of the former was found to be negatively correlated with ALS, while the latter was positively correlated with ALS incidence. While accepting that ALS is most probably multifactorial, it was concluded that sunlight deprivation and/or rainfall are associated to some degree with ALS incidence in Taiwan.

  13. Nervous system disease associated with dominant cellular radiosensitivity

    International Nuclear Information System (INIS)

    Kidson, C.; Chen, P.; Imray, F.P.; Gipps, E.

    1983-01-01

    Ionizing radiation sensitivity has been demonstrated in the following neurological diseases: sporadic and familial Alzheimer's disease, familial non-specific dementia, amyotrophic lateral sclerosis and Parkinsonism dementia of Guam, Huntington's disease, multiple sclerosis. Family studies in many cases give data consistent with dominant genetics, as does cell fusion analysis in the one disease so studied. In no case was there an absolute association between radiosensitivity and a given neurological disease. It is proposed that the underlying mutations are in genes controlling facets of nervous or immune system differentiation and development. 15 references, 2 tables

  14. Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Sowa, Piotr [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Owren Nygaard, Gro [Oslo University Hospital, Department of Neurology, Oslo (Norway); Bjoernerud, Atle [Intervention Center, Oslo University Hospital, Oslo (Norway); University of Oslo, Department of Physics, Oslo (Norway); Gulowsen Celius, Elisabeth [Oslo University Hospital, Department of Neurology, Oslo (Norway); University of Oslo, Institute of Health and Society, Faculty of Medicine, Oslo (Norway); Flinstad Harbo, Hanne [University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Oslo University Hospital, Department of Neurology, Oslo (Norway); Kristiansen Beyer, Mona [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Department of Life Sciences and Health, Oslo (Norway)

    2017-07-15

    The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

  15. Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Sowa, Piotr; Owren Nygaard, Gro; Bjoernerud, Atle; Gulowsen Celius, Elisabeth; Flinstad Harbo, Hanne; Kristiansen Beyer, Mona

    2017-01-01

    The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

  16. Central nervous system remyelination in culture — A tool for multiple sclerosis research

    Science.gov (United States)

    Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

    2011-01-01

    Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

  17. Central nervous system remyelination in culture--a tool for multiple sclerosis research.

    Science.gov (United States)

    Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

    2011-07-01

    Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Association between age at onset of multiple sclerosis and vitamin D level-related factors

    DEFF Research Database (Denmark)

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

    2016-01-01

    OBJECTIVE: To compare vitamin D level-associated single-nucleotide polymorphisms (SNPs) in GC and CYP2R1, multiple sclerosis (MS) risk SNPs in CYP27B1, CYP24A1, and HLA-DRB1*1501, and adolescent exposure to environmental risk factors for hypovitaminosis D, with MS age at onset. METHODS: This cross......, and the study was approved by the local ethics committee. RESULTS: Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher body mass index at 20 years of age, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis....... No association was found between age at onset and any of the other SNPs or vitamin D-associated environmental factors. CONCLUSION: We demonstrate an independent effect by HLA-DRB1*1501, adolescent summer sun habits, and body mass index at the age of 20 on age at onset of MS....

  19. Serum uric acid concentrations are directly associated with the presence of benign multiple sclerosis.

    Science.gov (United States)

    Simental-Mendía, Esteban; Simental-Mendía, Luis E; Guerrero-Romero, Fernando

    2017-09-01

    It has been reported that patients with multiple sclerosis (MS) exhibit lower serum uric acid levels; however, the association between uric acid concentrations and benign MS (BMS) has not been assessed. Hence, the objective of the present study was to determine whether the serum concentrations of uric acid are associated with the presence of BMS. Men and non-pregnant women over 16 years of age with diagnosis of MS were enrolled in a cross-sectional study. Expanded Disability Status Scale score acid were exclusion criteria. According to subtype of disease, the eligible patients were allocated into groups with BMS and other varieties of MS. A logistic regression analysis was conducted in order to evaluate the association between serum concentrations of uric acid and BMS. A total of 106 patients were included, 39 in the group with BMS and 67 in the group with other varieties of MS. The logistic regression analysis adjusted by age, sex, and disease duration showed that increased concentrations of uric acid, indeed within the physiological levels, are significantly associated with the presence of BMS (OR = 2.60; 95% CI: 1.55-4.38, p uric acid, indeed within the physiological range, are likely linked to the presence of BMS.

  20. CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.

    Science.gov (United States)

    Fardo, David W; Katsumata, Yuriko; Kauwe, John S K; Deming, Yuetiva; Harari, Oscar; Cruchaga, Carlos; Nelson, Peter T

    2017-04-01

    Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs). Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes. The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p<0.05 after Bonferroni correction). The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10 -5 ). Further, the rs5848 SNP status was associated with increased CSF tau protein - a marker of neurodegeneration (p=0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Global and regional brain atrophy is associated with low or retrograde facial vein flow in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Dejan Jakimovski

    2017-09-01

    Full Text Available Increased collateral facial vein (FV flow may be associated with structural damage in patients with multiple sclerosis (MS. The objective was to assess differences in FV flow and magnetic resonance imaging (MRI-derived outcomes in MS. The study included 136 MS patients who underwent neck and head vascular system examination by echo-color Doppler. Inflammatory MRI markers were assessed on a 3T MRI using a semi-automated edge detection and contouring/ thresholding technique. MRI volumetric outcomes of whole brain (WB, gray matter (GM, white matter (WM, cortex, ventricular cerebrospinal fluid (vCSF, deep gray matter (DGM, thalamus, caudate nucleus (CN, putamen, globus pallidus (GP, and hippocampus were calculated. Independent t-test and ANCOVA, adjusted for age, were used to compare groups based on FV flow quartiles. Thirty-four MS patients with FV flow ≤327.8 mL/min (lowest quartile had significantly lower WB (P327.8 mL/min (higher quartiles. There were no differences in T1-, T2- and gadolinium- enhancing lesion volumes between the quartile groups. The lack of an association between FV blood flow and inflammatory MRI measures in MS patients, but an association with brain atrophy, suggests that the severity of neurodegenerative process may be related to hemodynamic alterations. MS patients with more advanced global and regional brain atrophy showed low or retrograde FV volume flow.

  2. Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems.

    Directory of Open Access Journals (Sweden)

    Mireia Herrando-Grabulosa

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology, we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.

  3. A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Judith Field

    2010-10-01

    Full Text Available We conducted an association study across the human leukocyte antigen (HLA complex to identify loci associated with multiple sclerosis (MS. Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each P ≤ 4 x 10(-6. All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (P ≤ 0.001 and were highly significant in the combined dataset (P ≤ 6 x 10(-8. The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set P = 9 x 10(-9, replication set P = 7 x 10(-4, combined P = 2 x 10(-10. HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

  4. Computer use problems and accommodation strategies at work and home for people with systemic sclerosis: a needs assessment.

    Science.gov (United States)

    Baker, Nancy A; Aufman, Elyse L; Poole, Janet L

    2012-01-01

    We identified the extent of the need for interventions and assistive technology to prevent computer use problems in people with systemic sclerosis (SSc) and the accommodation strategies they use to alleviate such problems. Respondents were recruited through the Scleroderma Foundation. Twenty-seven people with SSc who used a computer and reported difficulty in working completed the Computer Problems Survey. All but 1 of the respondents reported one problem with at least one equipment type. The highest number of respondents reported problems with keyboards (88%) and chairs (85%). More than half reported discomfort in the past month associated with the chair, keyboard, and mouse. Respondents used a variety of accommodation strategies. Many respondents experienced problems and discomfort related to computer use. The characteristic symptoms of SSc may contribute to these problems. Occupational therapy interventions for computer use problems in clients with SSc need to be tested. Copyright © 2012 by the American Occupational Therapy Association, Inc.

  5. Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Simona Bonavita

    2013-01-01

    Full Text Available Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD, obsessive-compulsive disorder (OCD, bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS, euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions, which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

  6. Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis

    Science.gov (United States)

    Nakazawa, Seshiru; Oikawa, Daisuke; Ishii, Ryohei; Ayaki, Takashi; Takahashi, Hirotaka; Takeda, Hiroyuki; Ishitani, Ryuichiro; Kamei, Kiyoko; Takeyoshi, Izumi; Kawakami, Hideshi; Iwai, Kazuhiro; Hatada, Izuho; Sawasaki, Tatsuya; Ito, Hidefumi; Nureki, Osamu; Tokunaga, Fuminori

    2016-01-01

    Optineurin (OPTN) mutations cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and glaucoma. Although the ALS-associated E478G mutation in the UBAN domain of OPTN reportedly abolishes its NF-κB suppressive activity, the precise molecular basis in ALS pathogenesis still remains unclear. Here we report that the OPTN-UBAN domain is crucial for NF-κB suppression. Our crystal structure analysis reveals that OPTN-UBAN binds linear ubiquitin with homology to NEMO. TNF-α-mediated NF-κB activation is enhanced in OPTN-knockout cells, through increased ubiquitination and association of TNF receptor (TNFR) complex I components. Furthermore, OPTN binds caspase 8, and OPTN deficiency accelerates TNF-α-induced apoptosis by enhancing complex II formation. Immunohistochemical analyses of motor neurons from OPTN-associated ALS patients reveal that linear ubiquitin and activated NF-κB are partially co-localized with cytoplasmic inclusions, and that activation of caspases is elevated. Taken together, OPTN regulates both NF-κB activation and apoptosis via linear ubiquitin binding, and the loss of this ability may lead to ALS. PMID:27552911

  7. Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis.

    Science.gov (United States)

    D'hooghe, M B; Haentjens, P; Nagels, G; Garmyn, M; De Keyser, J

    2012-04-01

    Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS). We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS. We conducted a survey among persons with MS, registered by the Flemish MS society, Belgium, and stratified data according to relapsing-onset and progressive-onset MS. We used Kaplan-Meier survival and Cox proportional hazard regression analyses with time to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios for the time from onset and from birth were calculated for the potentially predictive variables, adjusting for age at onset, gender and immunomodulatory treatment. 704 (51.3%) of the 1372 respondents had reached EDSS 6. In relapsing-onset MS, respondents reporting equal or higher levels of sun exposure than persons of the same age in the last 10 years had a decreased risk of reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was associated with an increased hazard of reaching EDSS 6. The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS.

  8. An APOA1 promoter polymorphism is associated with cognitive performance in patients with multiple sclerosis.

    Science.gov (United States)

    Koutsis, G; Panas, M; Giogkaraki, E; Karadima, G; Sfagos, C; Vassilopoulos, D

    2009-02-01

    Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 -75G/A promoter polymorphism has been associated with elevated ApoA1 levels. We sought to investigate the effect of the APOA1 -75G/A promoter polymorphism on cognitive performance in patients with multiple sclerosis (MS). A total of 138 patients with MS and 43 controls were studied and underwent neuropsychological assessment with Rao's Brief Repeatable Battery and the Stroop test. All patients were genotyped for APOA1. APOA1 A-allele carriers displayed superior overall cognitive performance compared with non-carriers (P 0.008) and had a three-fold decrease in the relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11-0.74). Regarding performance on individual cognitive domains, although APOA1 A-allele carriers performed better than non-carriers on all tests, this was significant only for semantic verbal fluency and the Stroop interference task (P 0.036 and 0.018, respectively). We found an association of the APOA1 -75G/A promoter polymorphism with cognitive performance in MS. This effect was most prominent on semantic verbal fluency and the Stroop interference task.

  9. Vitamin D levels are associated with gross motor function in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Paganoni, Sabrina; Macklin, Eric A; Karam, Chafic; Yu, Hong; Gonterman, Fernando; Fetterman, K Ashley; Cudkowicz, Merit; Berry, James; Wills, Anne-Marie

    2017-10-01

    The objective of this study was to determine whether serum vitamin D [25(OH)D] levels are associated with disease progression in amyotrophic lateral sclerosis (ALS). 25(OH)D was measured in subjects enrolled in a multicenter study for validation of ALS biomarkers. Baseline 25(OH)D levels were correlated with baseline ALSFRS-R scores. Average 25(OH)D levels from baseline and month 6 visits (seasonally asynchronous) were used to predict subsequent rate of change in ALSFRS-R from month 6 to month 18. Most subjects had either insufficient or deficient 25(OH)D levels. Lower 25(OH)D was associated with lower ALSFRS-R gross motor scores, but not lower ALSFRS-R total scores at baseline. Levels of 25(OH)D were not predictive of disease progression over the next 12 months. 25(OH)D was associated with baseline gross motor ALSFRS-R scores but did not predict the rate of disease progression. Vitamin D levels may reflect poor mobility in patients with ALS. Muscle Nerve, 2017 Muscle Nerve 56: 726-731, 2017. © 2017 Wiley Periodicals, Inc.

  10. Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers: two case reports

    Directory of Open Access Journals (Sweden)

    Ughi N

    2016-03-01

    Full Text Available Nicola Ughi, Chiara Crotti, Francesca Ingegnoli Division of Rheumatology, Department of Clinical Sciences and Community Health, Gaetano Pini Institute, The University of Milan, Milan, Italy Abstract: Digital ulcers (DUs are a severe and frequent clinical feature of patients with systemic sclerosis (SSc. The presence of DUs may cause severe pain and often lead to impairment of patient’s functional activities and health-related quality of life. Moreover, poor patient cooperation during the wound care procedure due to pain may be associated with a negative outcome of DU healing. Therefore, pain management has a key role in patients with SSc. These two case reports describe the effectiveness and safety of oxycodone/naloxone in patients with SSc complicated by painful chronic DUs. Such a therapy has provided pain relief and consequently an increased compliance during redressing wounds. Keywords: oxycodone, naloxone, systemic sclerosis, pain, digital ulcer, scleroderma, analgaesia, wound healing, opioids, calcinosis, UCLA-SCTC GIT 2.0

  11. Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

    International Nuclear Information System (INIS)

    Kim, Ho Kyun; Lee, Hui Joong

    2013-01-01

    White matter hyper intensities (WMHI) on MRI are not rare in patients with progressive systemic sclerosis (PSS). In this presentation, WMHI were developed in both middle cerebellar peduncles and temporal white matter in a patient with PSS, and regressed after medication of high dose steroid. However, new lesions were developed in the subcortices of both precentral gyri, and progressed rapidly to tumefactive hyperintensity on MRI. We report an unusual relapsing and progressive tumefactive demyelinating form of central nervous system involvement in PSS.

  12. Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    C. Giacomelli

    2011-09-01

    Full Text Available Objective: Interstitial lung disease (ILD and pulmonary arterial hypertension (PAH are common complications of systemic sclerosis (SSc. Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC, i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILaD and PAH by integrated cardiac and chest ultrasound in SSc. Methods: We enrolled 30 consecutive SSc patients (age= 54±13 years, 23 females in the Rheumatology Clinic of Pisa University. In all, we assessed systolic pulmonary arterial pressure (SPAP, from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space. All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70, and antiicentromere associated with development of pulmonary involvement. Twenty-eight patients also underwent high resolution computed tomography, HRCT (from 0= no fibrosis to 3= honey combing. Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence Scl-70 antibodies. ULC number was similar in localized or diffuse forms (16±20 vs 21±19, p=ns and was unrelated to SPAP (r=0.216, p=ns. Conclusions: Chest sonography assessment and ULC allow a complete, simple, radiation-free characterization of interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies.

  13. Psychological characteristics of systemic sclerosis patients and their correlation with major organ involvement and disease activity.

    Science.gov (United States)

    Golemati, Christina V; Moutsopoulos, Haralampos M; Vlachoyiannopoulos, Panayiotis G

    2013-01-01

    The aim of this paper is to assess the psychological characteristics of personality, depression, anxiety, social support and coping strategies of systemic sclerosis (SSc) patients, their inter-correlations and their association with clinical symptoms. Patients with SSc (n=85) were interviewed and compared to rheumatoid arthritis (RA) patients (n=120) and healthy controls (HCs [n=125]). Psychological characteristics were assessed by the following psychometric scales: centre of epidemiological studies of depression (CES-D), hospital anxiety and depression scale (HAD), Eysenck personality questionnaire (EPQ), short form of social support (SSq), life experiences survey (LES) and ways of coping (WoC). Clinical data were collected at the same time of the interview. Both control groups were matched to SSc patients in terms of gender, age and educational status. Data were analysed with SPSS software. Compared to control groups, SSc patients expressed more symptoms of depression and anxiety, showed less extraversion and reported more negative life events. They coped less often with positive reappraisal, problem solving, seeking of support and assertiveness, while they sought more often divine help, and they expressed wishing and denial. Inactive disease was associated with a lower probability of reporting depressive symptoms and negative life events and with a higher probability of positively reevaluating a problem. Lung dysfunction, skin involvement, esophageal problems and oral aperture correlated with psychological features. Complications in psychological well-being characterise patients with SSc. This finding, as well as that of psychological characteristics correlating with organic factors, is an indication for designing supportive psycho-educational programmes as complementary therapies.

  14. Clinical algorithms for the diagnosis and prognosis of interstitial lung disease in systemic sclerosis.

    Science.gov (United States)

    Hax, Vanessa; Bredemeier, Markus; Didonet Moro, Ana Laura; Pavan, Thaís Rohde; Vieira, Marcelo Vasconcellos; Pitrez, Eduardo Hennemann; da Silva Chakr, Rafael Mendonça; Xavier, Ricardo Machado

    2017-10-01

    Interstitial lung disease (ILD) is currently the primary cause of death in systemic sclerosis (SSc). Thoracic high-resolution computed tomography (HRCT) is considered the gold standard for diagnosis. Recent studies have proposed several clinical algorithms to predict the diagnosis and prognosis of SSc-ILD. To test the clinical algorithms to predict the presence and prognosis of SSc-ILD and to evaluate the association of extent of ILD with mortality in a cohort of SSc patients. Retrospective cohort study, including 177 SSc patients assessed by clinical evaluation, laboratory tests, pulmonary function tests, and HRCT. Three clinical algorithms, combining lung auscultation, chest radiography, and percentage predicted forced vital capacity (FVC), were applied for the diagnosis of different extents of ILD on HRCT. Univariate and multivariate Cox proportional models were used to analyze the association of algorithms and the extent of ILD on HRCT with the risk of death using hazard ratios (HR). The prevalence of ILD on HRCT was 57.1% and 79 patients died (44.6%) in a median follow-up of 11.1 years. For identification of ILD with extent ≥10% and ≥20% on HRCT, all algorithms presented a high sensitivity (>89%) and a very low negative likelihood ratio (algorithms, especially the algorithm C (HR = 3.47, 95% CI: 1.62-7.42), which identified the presence of ILD based on crackles on lung auscultation, findings on chest X-ray, or FVC 20% on HRCT or, in indeterminate cases, FVC algorithms had a good diagnostic performance for extents of SSc-ILD on HRCT with clinical and prognostic relevance (≥10% and ≥20%), and were also strongly related to mortality. Non-HRCT-based algorithms could be useful when HRCT is not available. This is the first study to replicate the prognostic algorithm proposed by Goh et al. in a developing country. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Nailfold capillaroscopy for prediction of novel future severe organ involvement in systemic sclerosis.

    Science.gov (United States)

    Smith, Vanessa; Riccieri, Valeria; Pizzorni, Carmen; Decuman, Saskia; Deschepper, Ellen; Bonroy, Carolien; Sulli, Alberto; Piette, Yves; De Keyser, Filip; Cutolo, Maurizio

    2013-12-01

    Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma (systemic sclerosis; SSc) ("early," "active," and "late") with novel future severe clinical involvement in 2 independent cohorts. Sixty-six consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline. Images were blindly assessed and classified into normal, early, active, or late NVC pattern. Clinical evaluation was performed for 9 organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart, and kidney) according to the Medsger disease severity scale (DSS) at baseline and in the future (18-24 months of followup). Severe clinical involvement was defined as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous NVC predictor variable) was performed. The OR to develop novel future severe organ involvement was stronger according to more severe NVC patterns and similar in both cohorts. In simple logistic regression analysis the OR in the Belgian/Italian cohort was 2.16 (95% CI 1.19-4.47, p = 0.010)/2.33 (95% CI 1.36-4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern, and 10.14/12.63 for the late pattern versus the normal pattern. In multiple logistic regression analysis, adjusting for disease duration, subset, and vasoactive medication, the OR was 2.99 (95% CI 1.31-8.82, p = 0.007)/1.88 (95% CI 1.00-3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active pattern, and 26.69/6.66 for the late pattern versus the normal pattern. Capillaroscopy may be predictive of novel future severe organ involvement in SSc, as attested by 2 independent cohorts.

  16. An investigation into the association between HLA-G 14 bp insertion/deletion polymorphism and multiple sclerosis susceptibility.

    Science.gov (United States)

    Mohammadi, Nabiallah; Adib, Minoo; Alsahebfosoul, Fereshteh; Kazemi, Mohammad; Etemadifar, Masoud

    2016-01-15

    Human Leukocyte Antigen G (HLA-G) gene polymorphism and expression rate have recently been suggested to have a potential role in susceptibility to Multiple Sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. The aim of this study was to investigate the association of the frequency of HLA-G gene 14 bp insertion/deletion polymorphism and its plasma level with MS susceptibility. In this study, the HLA-G gene from 212 patients and 210 healthy individuals was amplified using real time PCR and screened for the 14 bp insertion/deletion polymorphism. In addition, HLA-G plasma levels of the patients were measured and compared to normal controls by ELISA method. Our results revealed that 14 bp insertion in HLA-G could result in lower plasma HLA-G level of the subjects, regardless of their health status and vice versa. Additionally, significant correlation of HLA-G genotype and its plasma level with MS susceptibility was observed. In conclusion, not only HLA-G 14 bp insertion/deletion polymorphism could be associated with expression rate of the HLA-G gene and its plasma level, but also could be considered as a risk factor for susceptibility to MS in our study population. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

    Science.gov (United States)

    Kappus, Natalie; Weinstock-Guttman, Bianca; Hagemeier, Jesper; Kennedy, Cheryl; Melia, Rebecca; Carl, Ellen; Ramasamy, Deepa P; Cherneva, Mariya; Durfee, Jacqueline; Bergsland, Niels; Dwyer, Michael G; Kolb, Channa; Hojnacki, David; Ramanathan, Murali; Zivadinov, Robert

    2016-02-01

    Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  18. Characteristics in childhood and adolescence associated with future multiple sclerosis risk in men: cohort study.

    Science.gov (United States)

    Gunnarsson, M; Udumyan, R; Bahmanyar, S; Nilsagård, Y; Montgomery, S

    2015-07-01

    Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated. A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination. Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P = 0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P = 0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS. © 2015 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  19. Self-esteem is associated with perceived stress in multiple sclerosis patients.

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    N Ifantopoulou, Parthena; K Artemiadis, Artemios; Triantafyllou, Nikolaos; Chrousos, George; Papanastasiou, Ioannis; Darviri, Christina

    2015-07-01

    Previous studies have showed that perceived stress (PS) in patients with multiple sclerosis (MS) constitutes an important factor for disease onset, relapse, symptomatology and psychological adjustment. The aim of this pilot cross-sectional study was to examine the role of self-esteem in PS, after controlling for sociodemographical characteristics, depression and personality in MS patients. Sixty-six relapsing-remitting MS patients (66.67% females, mean age of 40 ± 11.1 years old, mean duration of disease 133.6 ± 128.8 months) were studied. Perceived stress, self-esteem, depression and personality type were assessed using self-administered questionnaires. Hierarchical multivariate regression modelling was used. Higher education and depression and lower self-esteem were independently and significantly associated with increased PS, accounting for 40.5% of its variance. Univariate analyses revealed that low extroversion and openness and higher neurotism were associated with higher PS, although no significant after adjusting for other factors. Although our findings need further confirmation, psychological interventions targetting self-esteem are strongly encouraged.

  20. Driving competences and neuropsychological factors associated to driving counseling in multiple sclerosis.

    Science.gov (United States)

    Badenes, Dolors; Garolera, Maite; Casas, Laura; Cejudo-Bolivar, Juan Carlos; de Francisco, Jorge; Zaragoza, Silvia; Calzado, Noemi; Aguilar, Miquel

    2014-05-01

    Multiple Sclerosis (MS) significantly impacts daily living activities, including car driving. To investigate driving difficulties experienced with MS, we compared 50 MS patients with minor or moderate disability and 50 healthy controls (HC) using computerized driving tests (the ASDE driver test and the Useful Field of View (UFOV) test) and neuropsychological tests. Inclusion criteria included being active drivers. We evaluated whether cognitive deterioration in MS is associated with the results of driving tests by comparing MS patients without cognitive deterioration with HC. The results indicated that the MS patients performed worse than the HCs in attention, information processing, working memory and visuomotor coordination tasks. Furthermore, MS patients with cognitive impairments experienced more difficulties in the driving tests than did the non-impaired MS patients. Motor dysfunction associated with MS also played an important role in this activity. The results of this study suggest that MS should be assessed carefully and that special emphasis should be placed on visuomotor coordination and executive functions because patients with minor motor disability and subtle cognitive impairments can pass measures predictive of driving safety.

  1. Increased determinism in brain electrical activity occurs in association with multiple sclerosis.

    Science.gov (United States)

    Carrubba, Simona; Minagar, Alireza; Chesson, Andrew L; Frilot, Clifton; Marino, Andrew A

    2012-04-01

    Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). Ten subjects with a relapsing-remitting course of MS who were in remission were studied; the controls were age- and gender-matched clinically normal subjects. Recurrence plots were calculated using representative electroencephalogram (EEG) epochs (1-7 seconds) from six derivations; the plots were quantified using the nonlinear variables percent recurrence (%R) and percent determinism (%D). The results were averaged over all derivations for each participant, and the means were compared between the groups. As a linear control procedure the groups were also compared using spectral analysis. The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis. Taken together with our earlier report that %R could be used to discriminate between MS and normal subjects based on the ability to exhibit evoked potentials, the evidence suggests that complexity analysis of the EEG has potential for development as a diagnostic test for MS.

  2. Imbalance in multiple sclerosis and neuromyelitis optica: association with deep sensation disturbance.

    Science.gov (United States)

    Demura, Yutaka; Kinoshita, Masako; Fukuda, Osamu; Nose, Shouzou; Nakano, Hitoshi; Juzu, Akira; Murase, Nagako; Yamamoto, Kenji

    2016-12-01

    Abnormality in balance is one of the most important causes of gait disturbance which has a direct impact to disability and medical cost in multiple sclerosis (MS) and neuromyelitis optica (NMO). However, characteristics of imbalance in these two diseases have not been fully elucidated. The aim of this study was to evaluate the degree and features of imbalance using stabilography, the degree of deep sensation disturbance using tibial nerve somatosensory evoked potentials (SEP), and their association with clinical impairment, in patients with MS and NMO. Seven NMO patients and seven MS patients with balance disturbance were examined. The relationship among stabilography measurements representing the degree and features of imbalance, height-adjusted P38 peak latency of SEP, and neurological functional disability, were analyzed. Stabilography evaluation showed a significantly severer degree of imbalance in NMO than in MS. Romberg quotient of the patients with brainstem lesions was significantly larger than those without them. In all patients, length of excursion per second significantly correlated positively with anterio-posterior-axis power spectra at intermediate frequency band. In all patients and in NMO, P38 peak latency adjusted by height significantly correlated positively with anterio-posterior-axis power spectra at intermediate frequency band. These findings suggest that the degree of imbalance of MS and NMO possibly correlate with deep sensation disturbance, which could be evaluated by anterio-posterior-axis power spectra at intermediate frequency band by stabilography. Severer imbalance in NMO than MS may be associated with the severe longitudinally extensive spinal cord lesions.

  3. Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele

    2010-02-01

    Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.

  4. Disclosure of disease status among employed multiple sclerosis patients: association with negative work events and accommodations.

    Science.gov (United States)

    Frndak, Seth E; Kordovski, Victoria M; Cookfair, Diane; Rodgers, Jonathan D; Weinstock-Guttman, Bianca; Benedict, Ralph H B

    2015-02-01

    Unemployment is common in multiple sclerosis (MS) and detrimental to quality of life. Studies suggest disclosure of diagnosis is an adaptive strategy for patients. However, the role of cognitive deficits and psychiatric symptoms in disclosure are not well studied. The goals of this paper were to (a) determine clinical factors most predictive of disclosure, and (b) measure the effects of disclosure on workplace problems and accommodations in employed patients. We studied two overlapping cohorts: a cross-sectional sample (n = 143) to determine outcomes associated with disclosure, and a longitudinal sample (n = 103) compared at four time points over one year on reported problems and accommodations. A case study of six patients, disclosing during monitoring, was also included. Disclosure was associated with greater physical disability but not cognitive impairment. Logistic regression predicting disclosure status retained physical disability, accommodations and years of employment (p work problems and accommodations over time. The case study revealed that reasons for disclosing are multifaceted, including connection to employer, decreased mobility and problems at work. Although cognitive impairment is linked to unemployment, it does not appear to inform disclosure decisions. Early disclosure may help maintain employment if followed by appropriate accommodations. © The Author(s), 2014.

  5. Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Gleb Makshakov

    2017-01-01

    Full Text Available Leptomeningeal contrast enhancement (LMCE on magnetic resonance imaging (MRI is a newly recognized possible biomarker in multiple sclerosis (MS, associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR sequence. Expanded Disability Status Scale (EDSS score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54 of patients. LMCE-positive patients had longer disease duration (p=0,0098 and higher EDSS score (p=0,039, but not a higher relapse rate (p=0,091. No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected (p=0,3842. Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume (p=0.043, F=2.529, the total grey matter volume (p=0.043, F=2.54, and total ventricular volume (p=0.039, F=2.605. Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

  6. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

    Science.gov (United States)

    Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

    2009-12-08

    Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

  7. Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

    Science.gov (United States)

    García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

    2014-01-01

    Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

  8. A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chiò, Adriano; Schymick, Jennifer C; Restagno, Gabriella; Scholz, Sonja W; Lombardo, Federica; Lai, Shiao-Lin; Mora, Gabriele; Fung, Hon-Chung; Britton, Angela; Arepalli, Sampath; Gibbs, J Raphael; Nalls, Michael; Berger, Stephen; Kwee, Lydia Coulter; Oddone, Eugene Z; Ding, Jinhui; Crews, Cynthia; Rafferty, Ian; Washecka, Nicole; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Guralnik, Jack; Macciardi, Fabio; Torri, Federica; Lupoli, Sara; Chanock, Stephen J; Thomas, Gilles; Hunter, David J; Gieger, Christian; Wichmann, H Erich; Calvo, Andrea; Mutani, Roberto; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; La Bella, Vincenzo; Valentino, Francesca; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Siciliano, Gabriele; Carlesi, Cecilia; Orrell, Richard W; Talbot, Kevin; Simmons, Zachary; Connor, James; Pioro, Erik P; Dunkley, Travis; Stephan, Dietrich A; Kasperaviciute, Dalia; Fisher, Elizabeth M; Jabonka, Sibylle; Sendtner, Michael; Beck, Marcus; Bruijn, Lucie; Rothstein, Jeffrey; Schmidt, Silke; Singleton, Andrew; Hardy, John; Traynor, Bryan J

    2009-04-15

    The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

  9. Pain, Fatigue, and Cognitive Symptoms Are Temporally Associated Within but Not Across Days in Multiple Sclerosis.

    Science.gov (United States)

    Kratz, Anna L; Murphy, Susan L; Braley, Tiffany J

    2017-11-01

    To examine the temporal associations, within day and day to day, between pain, fatigue, depressed mood, and cognitive function in multiple sclerosis (MS). Repeated-measures study involving 7 days of ecological momentary assessment (EMA) of symptoms 5 times a day; multilevel mixed models were used to analyze data. Community. Ambulatory adults (N=107) with MS. Not applicable. EMA of pain, fatigue, depressed mood, and cognitive function rated on a 0 to 10 scale. Fatigue and pain were linked within day such that higher pain was associated with higher subsequent fatigue (B=.09, P=.04); likewise, higher fatigue was associated with higher pain in the following time frame (B=.05, P=.04). Poorer perceived cognitive function preceded increased subsequent pain (B=.08, P=.007) and fatigue (B=.10, P=.01) within day. Depressed mood was not temporally linked with other symptoms. In terms of day-to-day effects, a day of higher fatigue related to decreased next day fatigue (B=-.16, P=.01), and a day of higher depressed mood related to increased depressed mood the next day (B=.17, P=.01). There were no cross-symptom associations from one day to the next. Findings provide new insights on how common symptoms in MS relate to each other and vary within and over days. Pain and fatigue show evidence of a dynamic bidirectional relation over the course of a day, and worsening of perceived cognitive function preceded worsening of both pain and fatigue. Most temporal associations between symptoms occur within the course of a day, with relatively little carryover from one day to the next. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Gene Profiling in Patients with Systemic Sclerosis Reveals the Presence of Oncogenic Gene Signatures

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    Marzia Dolcino

    2018-03-01

    Full Text Available Systemic sclerosis (SSc is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma. The reason of this association is still unknown; therefore, we aimed at investigating whether particular genetic or epigenetic factors may play a role in promoting cancer development in patients with SSc and whether some features are shared by the two conditions. We therefore performed a gene expression profiling of peripheral blood mononuclear cells (PBMCs derived from patients with limited and diffuse SSc, showing that the various classes of genes potentially linked to the pathogenesis of SSc (such as apoptosis, endothelial cell activation, extracellular matrix remodeling, immune response, and inflammation include genes that directly participate in the development of malignancies or that are involved in pathways known to be associated with carcinogenesis. The transcriptional analysis was then complemented by a complex network analysis of modulated genes which further confirmed the presence of signaling pathways associated with carcinogenesis. Since epigenetic mechanisms, such as microRNAs (miRNAs, are believed to play a central role in the pathogenesis of SSc, we also evaluated whether specific cancer-related miRNAs could be deregulated in the serum of SSc patients. We focused our attention on miRNAs already found upregulated in SSc such as miR-21-5p, miR-92a-3p, and on miR-155-5p, miR 126-3p and miR-16-5p known to be deregulated in malignancies associated to SSc, i.e., breast, lung, and hematological malignancies. miR-21-5p, miR-92a-3p, miR-155-5p, and miR-16-5p expression was significantly higher in SSc sera compared to

  11. Assessment of nailfold capillaroscopy in systemic sclerosis by different optical magnification methods.

    Science.gov (United States)

    Mazzotti, N G; Bredemeier, M; Brenol, C V; Xavier, R M; Cestari, T F

    2014-03-01

    Systemic sclerosis (SSc) is characterized by target-organ fibrosis and microvascular dysfunction, which can be assessed using nailfold capillaroscopy. Dermoscopy is a useful and easily performed method for diagnosing skin lesions. To compare conventional capillaroscopy, using the gold-standard method (conventional stereomicroscope nailfold capillaroscopy; SNFC), with polarized light noncontact dermoscopy (PNCD) and nonpolarized light contact dermoscopy (NPCD), and to evaluate their accuracy in diagnosing characteristic SSc-related alterations. The study enrolled 45 patients with SSc. Capillaroscopy images and photographs were taken with three devices, SNFC, NPCD and PNCD, and these images were randomly analysed by a blinded observer. The scleroderma pattern was found in 83% of patients. PNCD and NPCD were highly sensitive in identifying the presence of focal capillary loss (96.4% and 100%, respectively), haemorrhage (96.2% and 92%, respectively), and scleroderma (91.9%, 94.6%), and showed high specificity for haemorrhage and enlarged loops. The intra-observer kappa values for detection of the scleroderma pattern by SNFC images, NPCD and PNCD were moderate to good: (κ = 0.71 (95% CI 0.44-0.95), κ = 0.60 (95% CI 0.35-0.83) and κ = 0.60 (95% CI 0.32-0.86), respectively. Evaluation of haemorrhage presence gave high kappa values for all methods: κ = 0.77 (95% CI 0.57-0.95), κ = 0.90 (95% CI 0.76-1.00) and κ = 0.95 (95% CI 0.85-1.00), respectively. Both polarized and nonpolarized dermoscopy are reliable methods for valuation of nailfold capillaroscopy in patients with SSc. They are easy to perform, with good rates of accuracy and results that are comparable with traditional capillaroscopy. © 2013 British Association of Dermatologists.

  12. Survival, causes of death, and prognostic factors in systemic sclerosis: analysis of 947 Brazilian patients.

    Science.gov (United States)

    Sampaio-Barros, Percival D; Bortoluzzo, Adriana B; Marangoni, Roberta G; Rocha, Luiza F; Del Rio, Ana Paula T; Samara, Adil M; Yoshinari, Natalino H; Marques-Neto, João Francisco

    2012-10-01

    To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS < 20). Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc.

  13. Familial autoimmunity and polyautoimmunity in 60 Brazilian Midwest patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Alex Magno Coelho Horimoto

    Full Text Available ABSTRACT Introduction: Systemic sclerosis (SSc is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS, as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%, Sjögren's syndrome (38.5%, and inflammatory myopathy (11.5%. The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%, rheumatoid arthritis (22.6%, and SLE (22.6%. The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a

  14. Esophageal and anorectal involvement in systemic sclerosis: a systematic assessment with high resolution manometry.

    Science.gov (United States)

    Luciano, Laure; Granel, Brigitte; Bernit, Emmanuelle; Harle, Jean-Robert; Baumstarck, Karine; Grimaud, Jean-Charles; Bouvier, Michel; Vitton, Véronique

    2016-01-01

    In systemic sclerosis (SSc), esophageal and anorectal involvements are frequent and often associated with each other. In clinical practice, esophageal explorations are often prescribed, while anorectal explorations are rarely proposed and therefore, under-recognised. However, it is well documented in the literature that early detection of anorectal dysfunction could delay and/or prevent the onset of symptoms such as fecal incontinence (FI). The main objective was the systematic evaluation and detection of esophageal and anorectal involvements in SSc patients. In this monocentric retrospective study, all patients with SSc addressed in the Department of Functional Digestive Explorations, North Hospital, Marseille for esophageal and anorectal explorations were included. Self-Questionnaires, evaluating the symptoms and quality of life, were filled by patients during their visit. Explorations were performed on the same day: high resolution esophageal manometry (EHRM), 3 Dimensional high resolution anorectal manometry (3DHRARM) and endo anal sonography (EUS). 44 patients (41 women), mean age 59.8±12 years, were included. With regard to the symptoms, 45.5% of patients had gastro-esophageal reflux disease (GERD), 66.9% dysphagia, 65.9% constipation and 77.3% FI. The incidence of esophageal dismotility was 65.9%, anorectal and both upper and lower dysfunction were 43.2%. More than 89% patients with abnormal explorations (EHRM, 3DHRARM or both) were symptomatic. Duration of SSc and altered quality of life was correlated with the severity of digestive involvement. Anorectal dysfunction appears to be closely linked to esophageal involvement in SSc. Their routine screening is undoubtedly essential to limit the occurrence of severe symptoms such as FI.

  15. Specific central nervous system recruitment of HLA-G(+) regulatory T cells in multiple sclerosis.

    Science.gov (United States)

    Huang, Yu-Hwa; Zozulya, Alla L; Weidenfeller, Christian; Metz, Imke; Buck, Dorothea; Toyka, Klaus V; Brück, Wolfgang; Wiendl, Heinz

    2009-08-01

    We have recently described a novel population of natural regulatory T cells (T(reg)) that are characterized by the expression of HLA-G and may be found at sites of tissue inflammation (HLA-G(pos) T(reg)). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS). Sixty-four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA-G(pos) T(reg) were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood-brain barrier (BBB). HLA-G(pos) T(reg) were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA-G(pos) T(reg) showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF-derived HLA-G(pos) T(reg) of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3-expressing T(reg), HLA-G(pos) T(reg) derived from peripheral blood were functionally unimpaired in MS. In MS, HLA-G(pos) T(reg) may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS.

  16. Sun exposure over the life course and associations with multiple sclerosis.

    Science.gov (United States)

    Tremlett, Helen; Zhu, Feng; Ascherio, Alberto; Munger, Kassandra L

    2018-04-03

    To examine sun exposure and multiple sclerosis (MS) over the life course (ages 5-15 and 16-20 years, every 10 years thereafter). Cases with MS (n = 151) and age-matched controls (n = 235) from the Nurses' Health Study cohorts completed summer, winter, and lifetime sun exposure history questionnaires. Cumulative ambient ultraviolet (UV)-B (based on latitude, altitude, cloud cover) exposure before MS onset was expressed as tertiles. Seasonal sun exposure was defined as low vs high hours per week (summer [≤9 vs >10 h/wk]; winter [≤3 vs >4 h/wk]). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated via conditional logistic regression with adjustment for body mass index, ancestry, smoking, and vitamin D supplementation. Most participants were white (98%); the mean age at MS onset was 39.5 years. Living in high (vs low) UV-B areas before MS onset was associated with a 45% lower MS risk (adjusted RR 0.55, 95% CI 0.42-0.73). Similar reduced risks (51%-52%) for medium or high exposure were observed at ages 5 to 15 years and at 5 to 15 years before MS onset (adjusted p sun exposure were associated with a lower MS risk (RR 0.45, 95% CI 0.21-0.96). Living in high ambient UV-B areas during childhood and the years leading up to MS onset was associated with a lower MS risk. High summer sun exposure in high ambient UV-B areas was also associated with a reduced risk. © 2018 American Academy of Neurology.

  17. CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

    Science.gov (United States)

    Alcina, Antonio; Teruel, María; Díaz-Gallo, Lina M.; Gómez-García, María; López-Nevot, Miguel A.; Rodrigo, Luis; Nieto, Antonio; Cardeña, Carlos; Alcain, Guillermo; Díaz-Rubio, Manuel; de la Concha, Emilio G.; Fernandez, Oscar; Arroyo, Rafael

    2010-01-01

    Background A functional polymorphism located at −1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions. Methodology Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93–1.17)]. Conclusion The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions. PMID:20634952

  18. Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms.

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    J Matthew Mahoney

    2015-01-01

    Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected

  19. Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis

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    Antonietta eGentile

    2015-06-01

    Full Text Available Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioural alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, they can regulate synaptic activity, thereby leading to perturbation of behaviour.In multiple sclerosis (MS, the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioural studies in experimental autoimmune encephalomyelitis (EAE, the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioural syndrome. We review the experimental studies addressing behavioural symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS.

  20. Assessment of working memory in patients with mesial temporal lobe epilepsy associated with unilateral hippocampal sclerosis.

    Science.gov (United States)

    Tudesco, Ivanda de Souza Silva; Vaz, Leonardo José; Mantoan, Marcele Araújo Silva; Belzunces, Erich; Noffs, Maria Helena; Caboclo, Luís Otávio Sales Ferreira; Yacubian, Elza Márcia Targas; Sakamoto, Américo Ceiki; Bueno, Orlando Francisco Amodeo

    2010-07-01

    The aim of the present study was to investigate whether working memory is impaired in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), a controversial and largely unexplored matter. Twenty subjects with left MTLE-HS, 19 with right MTLE-HS, and 21 control right-handed subjects underwent neuropsychological assessment of episodic and semantic memory, executive functions, and specific working memory components. Left and right epileptogenic foci resulted in impairment of verbal and nonverbal episodic memory (verbal memory deficit greater in left MTLE-HS than in right MTLE-HS). In addition, patients with left MTLE-HS were impaired in learning paired associates, verbal fluency, and Trail Making. No differences were seen in the tests carried out to evaluate the working memory components (except visuospatial short-term memory in right MTLE-HS). In this study we did not detect reliable working memory impairment in patients with MTLE-HS with either a left or right focus in most tasks considered as tests of working memory components. Copyright 2010 Elsevier Inc. All rights reserved.

  1. The diagnostic imaging and interventional therapy of hepatic angiomyolipoma associated with tuberous sclerosis

    International Nuclear Information System (INIS)

    You Jian; Xu Wei; Zhu Jiehui

    2001-01-01

    Objective: To evaluate imaging diagnosis, differential diagnosis, surgery and interventional therapy of hepatic angiomyolipoma associated with tuberous sclerosis. Methods: Clinical features, imaging appearances and interventional therapy for 2 cases of HAML in TS were retrospectively analyzed. Results: The features of HAML in TS are as following: (1) Two cases were female with no history of hepatitis and hepatocirrhosis, liver function test and alpha fetoprotein were normal: (2) the tumor was shown as a multiple hyper-echoic mass with sharp margin on ultrasonography; well defined, fat density and intensity mass on computerized tomography (CT); hypervascular mass with early drainage of hepatic vein and tumor staining on angiography. (3) One case underwent interventional therapy. After 42 month follow up, the tumor was found to be diminished in size. Another case was under monitored with only the enucleating of left renal mass. The hepatic tumor showed no change after 10 months. Conclusions: The imaging appearances of HAML in TS are relatively characteristic. Super selective arterial embolization is an effective treatment for HAML in TS

  2. T-cell receptor Vα and Cα alleles associated with multiple sclerosis and myasthenia gravis

    International Nuclear Information System (INIS)

    Oksenberg, J.R.; Cavalli-Sforza, L.L.; Steinman, L.; Sherritt, M.; Bernard, C.C.; Begovich, A.B.; Erlich, H.A.

    1989-01-01

    Polymorphic markers in genes encoding the α chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, the authors amplified selected sequences derived from the full-length TcR α cDNA probe. These PcR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of the polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, the authors have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V α and C α markers were identified between patients and healthy individuals

  3. A novel missense mutation of the DDHD1 gene associated with juvenile amyotrophic lateral sclerosis

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    Chujun Wu

    2016-12-01

    Full Text Available Background: Juvenile amyotrophic lateral sclerosis (jALS is a rare form of ALS with an onset age of less than 25 years and is frequently thought to be genetic in origin. DDHD1 gene mutations have been reported to be associated with the SPG28 subtype of autosomal recessive HSP but have never been reported in jALS patients.Methods: Gene screens for the causative genes of ALS, HSP and CMT using next-generation sequencing (NGS technologies were performed on a jALS patient. Sanger sequencing was used to validate identified variants and perform segregation analysis.Results: We identified a novel c.1483A>G (p.Met495Val homozygous missense mutation of the DDHD1 gene in the jALS patient. All of his parents and young bother were heterozygous for this mutation. The mutation was not found in 800 Chinese control subjects or the data of dbSNP, ExAC and 1000G.Conclusion: The novel c.1483A>G (p.Met495Val missense mutation of the DDHD1 gene could be a causative mutation of autosomal recessive jALS.

  4. Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

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    Georgios Koutsis

    2015-01-01

    Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

  5. Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

    Science.gov (United States)

    Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

    2015-01-01

    We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

  6. Depression and anxiety in a case series of amyotrophic lateral sclerosis: frequency and association with clinical features.

    Science.gov (United States)

    Prado, Laura de Godoy Rousseff; Bicalho, Isabella Carolina Santos; Vidigal-Lopes, Mauro; Prado, Vitor de Godoy Rousseff; Gomez, Rodrigo Santiago; de Souza, Leonardo Cruz; Teixeira, Antônio Lúcio

    2017-01-01

    To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis. This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji's criteria. Patients underwent clinical and psychiatric assessment (anxiety and depression symptoms). We included 76 patients. The men/women ratio was 1.6:1. Participants' mean age at disease onset was 55 years (SD±12.1). Sixty-six patients (86.8%) were able to complete psychiatric evaluation. Clinically significant anxiety was found in 23 patients (34.8%) while clinically significant depression was found in 24 patients (36.4%). When we compared patients with and without depression a significant difference was seen only in the frequency of anxiety symptoms (pescala funcional. Foi encontrada correlação positiva entre os sintomas de ansiedade e depressão (pescala funcional.

  7. Rehabilitation in multiple sclerosis.

    Science.gov (United States)

    Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

    2017-07-01

    The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

  8. System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice.

    Science.gov (United States)

    Mesci, Pinar; Zaïdi, Sakina; Lobsiger, Christian S; Millecamps, Stéphanie; Escartin, Carole; Seilhean, Danielle; Sato, Hideyo; Mallat, Michel; Boillée, Séverine

    2015-01-01

    Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression. However, microglial-derived neurotoxic factors still remain largely unidentified in amyotrophic lateral sclerosis. With excitotoxicity being a major mechanism proposed to cause motor neuron death in amyotrophic lateral sclerosis, our hypothesis was that excessive glutamate release by activated microglia through their system [Formula: see text] (a cystine/glutamate antiporter with the specific subunit xCT/Slc7a11) could contribute to neurodegeneration. Here we show that xCT expression is enriched in microglia compared to total mouse spinal cord and absent from motor neurons. Activated microglia induced xCT expression and during disease, xCT levels were increased in both spinal cord and isolated microglia from mutant SOD1 amyotrophic lateral sclerosis mice. Expression of xCT was also detectable in spinal cord post-mortem tissues of patients with amyotrophic lateral sclerosis and correlated with increased inflammation. Genetic deletion of xCT in mice demonstrated that activated microglia released glutamate mainly through system [Formula: see text]. Interestingly, xCT deletion also led to decreased production of specific microglial pro-inflammatory/neurotoxic factors including nitric oxide, TNFa and IL6, whereas expression of anti-inflammatory/neuroprotective markers such as Ym1/Chil3 were increased, indicating that xCT regulates microglial functions. In amyotrophic lateral sclerosis mice, xCT deletion surprisingly led to earlier symptom onset but, importantly, this was followed by a significantly slowed progressive disease phase, which resulted in more surviving motor neurons. These results are consistent with a deleterious contribution of microglial-derived glutamate during symptomatic

  9. The Association of −330 Interleukin-2 Gene Polymorphism with Its Plasma Concentration in Iranian Multiple Sclerosis Patients

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    Arezou Sayad

    2014-01-01

    Full Text Available Multiple sclerosis (MS is a chronic neuroinflammatory demyelinating disease of the central nervous system. The cytokine genes are involved in autoimmune diseases such as MS. In this study, we report the influence of −330 interleukin-2 (IL2 gene polymorphism on its plasma levels in a group of Iranian MS patients. In this study 100 MS patients and 100 ethnically, age, and sex matched healthy controls were selected from Medical Genetics Department of Sarem Women Hospital. Blood samples of all individuals were collected in EDTA tubes. The restriction fragment length polymorphism PCR (RFLP method was applied to determine various alleles and genotypes in these individuals. Plasma concentration of IL2 was measured in all the samples using human IL2 kit. The frequency of −330 T/T IL2 genotype was higher in MS patients compared to normal individuals. Accordingly, the plasma levels of IL2 were significantly higher (P<0.0001 in patients when compared to the control group. In conclusion, in case of MS patients the −330 T/T IL2 genotype is associated with higher plasma levels of IL2.

  10. No association between dietary sodium intake and the risk of multiple sclerosis.

    Science.gov (United States)

    Cortese, Marianna; Yuan, Changzheng; Chitnis, Tanuja; Ascherio, Alberto; Munger, Kassandra L

    2017-09-26

    To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk. In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984-2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991-2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models. Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 0.98, 95% CI 0.74-1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 1.02, 95% CI 0.76-1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results ( p for trend = 0.95). Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS. © 2017 American Academy of Neurology.

  11. Meta-analytic evaluation of the association between head injury and risk of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Watanabe, Yukari; Watanabe, Takamitsu

    2017-10-01

    Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case-control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016. After selecting appropriate publications based on PRISMA statement, we performed random-effects meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixteen of 825 studies fulfilled the eligibility criteria. The association between head injuries and ALS was statistically significant when the meta-analysis included all the 16 studies (OR 1.45, 95% CI 1.21-1.74). However, in the meta-analyses considering the time lags between the experience of head injuries and diagnosis of ALS, the association was weaker (OR 1.21, 95% CI 1.01-1.46, time lag ≥ 1 year) or not significant (e.g. OR 1.16, 95% CI 0.84-1.59, time lag ≥ 3 years). Although it did not deny associations between head injuries and ALS, the current study suggests a possibility that such a head-injury-oriented risk of ALS has been somewhat overestimated. For more accurate evaluation, it would be necessary to conduct more epidemiological studies that consider the time lags between the occurrence of head injuries and the diagnosis of ALS.

  12. Novel functional polymorphism in IGF-1 gene associated with multiple sclerosis: A new insight to MS.

    Science.gov (United States)

    Shahbazi, Majid; Abdolmohammadi, Reza; Ebadi, Hamid; Farazmandfar, Touraj

    2017-04-01

    Interactions between several genes and environment may play a role in susceptibility to multiple sclerosis (MS). The IGF-1 plays a key role in proliferation, maintenance and survival of nerve cells. Therefore, we hypothesized that IGF-1 may be a target for prediction and control MS. We aimed to analysis IGF-1 gene promoter sequence, to investigate the effect of the single nucleotide variants on IGF-1 expression and its association with MS. We enrolled 339 MS patients and 431 healthy controls. A specific region in IGF-1 gene promoter was investigated by SSCP analysis. All samples were genotyped by SSP-PCR. In-vitro and in-vivo IGF-1 production was measured by ELISA assay. IGF-1 expression in PBMCs was measured using real-time PCR. We identified a T to C single nucleotide substitution at position -1089 and a C to T at position -383 from transcription start site in the IGF-1 gene promoter. There was a significant association between MS and genotypes IGF-1(-383) C/T (p=0.001) and IGF-1(-383) C/C (pMS (p=0.001). In-vitro and in-vivo IGF-1 level showed that IGF-1 production in samples with genotype IGF-1(-383) C/C significantly was less than T/T (p=0.004) but not T/C (p=0.220). According to IGF-1 roles in CNS and our results, this study suggests that low IGF-1 level may be associated with susceptibility to MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.

    Science.gov (United States)

    Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa

    2017-06-01

    Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing T H 1 cells or interleukin (IL)-17-producing T H 17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of T H 17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

  14. Association between change in normal appearing white matter metabolites and intrathecal inflammation in natalizumab-treated multiple sclerosis.

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    Johan Mellergård

    Full Text Available BACKGROUND: Multiple sclerosis (MS is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS. Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM. METHODS: Quantitative proton magnetic resonance spectroscopy ((1H-MRS was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in (1H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients. RESULTS: The group levels of (1H-MRS metabolite concentrations were unchanged pre- to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43-0.67, p<0.0005-0.03 were found between changes in individual metabolite concentrations (total creatine and total choline and levels of pro-inflammatory markers (IL-1β and CXCL8. CONCLUSIONS: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in (1H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.

  15. TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update.

    Science.gov (United States)

    Lattante, Serena; Rouleau, Guy A; Kabashi, Edor

    2013-06-01

    Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP-43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP-43 positive inclusion bodies were first discovered in ubiquitin-positive, tau-negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C-terminus of the proteins. The molecular mechanisms through which mutant TDP-43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS. © 2013 Wiley Periodicals, Inc.

  16. Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis.

    Science.gov (United States)

    Velazquez-Villoria, D; Macia-Badia, C; Segura-García, A; Pastor Idoate, S; Arcos-Algaba, G; Velez-Escola, L; García-Arumí, J

    2017-06-01

    To analyse the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. Uveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1-10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-β or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (P=.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. Interferon β or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

    Science.gov (United States)

    van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

    2014-06-25

    High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year

  18. Impaired quality of life in patients with systemic sclerosis compared to the general population and chronic dermatoses.

    Science.gov (United States)

    Bretterklieber, Agnes; Painsi, Clemens; Avian, Alexander; Wutte, Nora; Aberer, Elisabeth

    2014-09-02

    Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the normal population, SSc patients from other studies, and patients with chronic skin diseases. For the most part, our SSc patients had better outcomes in all 8 dimensions of the SF-36 than SSc patients from other studies, and poorer scores than the healthy population and those with occupational contact dermatitis, ichthyosis, non-melanoma skin cancer, contact dermatitis, atopic eczema, chronic nail disease, vitiligo, health care workers with work-related disease, and those with other chronic skin diseases, but significantly better scores for mental health than those with nail disease, vitiligo, and health-care workers. Patients with atopic dermatitis, psoriasis and pemphigus had significantly poorer mean scores in social function and mental health than SSc patients. Patients with pemphigus were also significantly impaired in their physical and emotional roles. Patients with systemic lupus erythematosus (SLE) had the significantly poorest mean scores for QoL in all 8 domains except bodily pain and emotional role. Besides SLE, SSc is one of the most severe chronic dermatologic diseases in terms of reduced QoL. Since SSc cannot be cured, treatment strategies should include therapeutic interventions such as psychotherapy, social support, physiotherapy, and spiritual care. Their beneficial effects could be studied in future.

  19. Nailfold Capillaroscopy and Clinical Applications in Systemic Sclerosis.

    Science.gov (United States)

    Smith, Vanessa; Thevissen, Kristof; Trombetta, Amelia C; Pizzorni, Carmen; Ruaro, Barbara; Piette, Yves; Paolino, Sabrina; De Keyser, Filip; Sulli, Alberto; Melsens, Karin; Cutolo, Maurizio

    2016-07-01

    Capillary microscopy is a safe and non-invasive tool to evaluate the morphology of the microcirculation typically affected in SSc. Next to being paramount for the "(very) early" diagnosis of SSc eyes are also geared toward capillaroscopy with the aim to be able to use it as a biomarker, especially in the prediction of future occurrence of DU. The following review will explain what capillary microscopy is and will focus additionally on studies evaluating the association between capillaroscopy and DU. © 2016 John Wiley & Sons Ltd.

  20. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR)

    NARCIS (Netherlands)

    Kowal-Bielecka, O.; Landewé, R.; Avouac, J.; Chwiesko, S.; Miniati, I.; Czirjak, L.; Clements, P.; Denton, C.; Farge, D.; Fligelstone, K.; Földvari, I.; Furst, D. E.; Müller-Ladner, U.; Seibold, J.; Silver, R. M.; Takehara, K.; Toth, B. Garay; Tyndall, A.; Valentini, G.; van den Hoogen, F.; Wigley, F.; Zulian, F.; Matucci-Cerinic, Marco

    2009-01-01

    The optimal treatment of systemic sclerosis (SSc) is a challenge because the pathogenesis of SSc is unclear and it is an uncommon and clinically heterogeneous disease affecting multiple organ systems. The aim of the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group

  1. Association between MRI structural features and cognitive measures in pediatric multiple sclerosis

    Science.gov (United States)

    Amoroso, N.; Bellotti, R.; Fanizzi, A.; Lombardi, A.; Monaco, A.; Liguori, M.; Margari, L.; Simone, M.; Viterbo, R. G.; Tangaro, S.

    2017-09-01

    Multiple sclerosis (MS) is an inflammatory and demyelinating disease associated with neurodegenerative processes that lead to brain structural changes. The disease affects mostly young adults, but 3-5% of cases has a pediatric onset (POMS). Magnetic Resonance Imaging (MRI) is generally used for diagnosis and follow-up in MS patients, however the most common MRI measures (e.g. new or enlarging T2-weighted lesions, T1-weighted gadolinium- enhancing lesions) have often failed as surrogate markers of MS disability and progression. MS is clinically heterogenous with symptoms that can include both physical changes (such as visual loss or walking difficulties) and cognitive impairment. 30-50% of POMS experience prominent cognitive dysfunction. In order to investigate the association between cognitive measures and brain morphometry, in this work we present a fully automated pipeline for processing and analyzing MRI brain scans. Relevant anatomical structures are segmented with FreeSurfer; besides, statistical features are computed. Thus, we describe the data referred to 12 patients with early POMS (mean age at MRI: 15.5 +/- 2.7 years) with a set of 181 structural features. The major cognitive abilities measured are verbal and visuo-spatial learning, expressive language and complex attention. Data was collected at the Department of Basic Sciences, Neurosciences and Sense Organs, University of Bari, and exploring different abilities like the verbal and visuo-spatial learning, expressive language and complex attention. Different regression models and parameter configurations are explored to assess the robustness of the results, in particular Generalized Linear Models, Bayes Regression, Random Forests, Support Vector Regression and Artificial Neural Networks are discussed.

  2. Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.

    Science.gov (United States)

    Hughes, Abbey J; Parmenter, Brett A; Haselkorn, Jodie K; Lovera, Jesus F; Bourdette, Dennis; Boudreau, Eilis; Cameron, Michelle H; Turner, Aaron P

    2017-08-01

    Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self-reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi-centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self-reported sleep measures. Nearly two-thirds (65%) of participants met the criteria for 'poor' sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self-reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self-reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self-reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self-reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation. © 2017 European Sleep Research Society.

  3. Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.

    Science.gov (United States)

    Kolbe, Scott C; Kilpatrick, Trevor J; Mitchell, Peter J; White, Owen; Egan, Gary F; Fielding, Joanne

    2014-05-01

    Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients. Copyright © 2013 Wiley Periodicals, Inc.

  4. Novel Mutation in the TSC2 Gene Associated with Prenatally Diagnosed Cardiac Rhabdomyomas and Cerebral Tuberous Sclerosis

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2006-01-01

    Full Text Available Cardiac rhabdomyomas are prenatal echocardiographic markers for tuberous sclerosis complex (TSC. TSC is caused by mutations in the genes TSC1 and TSC2. We report a 28-year-old, gravida 5, para 2, woman with an uncomplicated pregnancy until prenatal ultrasound at 34 weeks' gestation revealed fetal cardiac tumors. Ultrafast magnetic resonance imaging (MRI at 36 weeks' gestation showed cardiac rhab-domyomas and small subependymal tubers. At 39 weeks' gestation, a 2262 g female infant was delivered uneventfully. Postnatal echocardiography confirmed cardiac rhabdomyomas and MRI verified small cerebral subependymal tubers. Mutational analysis of TSC1 and TSC2 genes using denaturing high-performance liquid chromatography and direct sequencing of the genes was performed and revealed that the parents had wildtype DNA, while the proband was heterozygous for a novel de novo nonsense mutation, c.4830 G > A, in exon 36 of the TSC2 gene, resulting in a change of codon 1610 TGG (tryptophan to TGA (stop codon. The mutation predicted a W1610X premature termination of the tuberin protein. These findings support an association between a TSC2 de novo nonsense mutation and prenatally detected cardiac rhabdomyomas and cerebral tuberous sclerosis. Familial molecular analysis of TSC1 and TSC2 in cases with prenatally diagnosed cardiac rhabdomyomas and cerebral tuberous sclerosis lesions is helpful in prenatal diagnosis and genetic counseling.

  5. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis

    DEFF Research Database (Denmark)

    Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta

    2015-01-01

    OBJECTIVE: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. METHODS: Data collected between June 2004 and April 2013 were examined with focus on capillar......OBJECTIVE: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. METHODS: Data collected between June 2004 and April 2013 were examined with focus...... on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. RESULTS: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy...... in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. CONCLUSION: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern...

  6. Multiple sclerosis documentation system (MSDS): moving from documentation to management of MS patients.

    Science.gov (United States)

    Ziemssen, Tjalf; Kempcke, Raimar; Eulitz, Marco; Großmann, Lars; Suhrbier, Alexander; Thomas, Katja; Schultheiss, Thorsten

    2013-09-01

    The long disease duration of multiple sclerosis and the increasing therapeutic options require a individualized therapeutic approach which should be carefully documented over years of observation. To switch from MS documentation to an innovative MS management, new computer- and internet-based tools could be implemented as we could demonstrate with the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). MSDS 3D allows documentation and management of visit schedules and mandatory examinations via defined study modules by integration of data input from various sources (patients, attending physicians and MS nurses). It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information can be collected via interactive touch screens. Specific modules allow the management of highly efficacious treatments as natalizumab or fingolimod. MSDS can be used to transfer the documented data to databases as, e.g. the registry of the German MS society or REGIMS. MSDS has already been implemented successfully in clinical practice and is currently being evaluated in a multicenter setting. High-quality management and documentation are crucial for improvements in clinical practice and research work.

  7. Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Steen, V.D.; Uretsky, B.F.; Owens, G.R.; Rodnan, G.P.

    1984-01-01

    To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury

  8. Reduced levels of S-nitrosothiols in plasma of patients with systemic sclerosis and Raynaud's phenomenon.

    Science.gov (United States)

    Kundu, Devi; Abraham, David; Black, Carol M; Denton, Christopher P; Bruckdorfer, K Richard

    2014-12-01

    S-Nitrosothiols (RSNOs) are bioactive forms of nitric oxide which are involved in cell signalling and redox regulation of vascular function. Circulating S-nitrosothiols are predominantly in the form of S-nitrosoalbumin. In this study plasma concentrations of S-nitrosothiols were measured in patients with systemic sclerosis (SSc) where NO metabolism is known to be abnormal. Venous blood was collected from 16 patients with Raynaud's phenomenon (RP), 45 with systemic sclerosis (SSc) (34 patients had limited SSc (IcSSc) and 11 diffuse cutaneous disease (dcSSc)). Twenty six healthy subjects were used as controls. Plasma S-nitrosothiol concentrations were measured by chemiluminescence. The measurements were related to the extent of biological age, capillary/skin scores and disease duration. Plasma RSNO levels in patients with Raynaud's phenomenon (RP) and in those with SSc was significantly lower compared to the concentrations in control subjects. In SSc, plasma S-nitrosothiols were often below the level of detection (1nM). Low S-nitrosothiol concentrations were observed in the blood of patients with SSc and patients with RP indicating a profound disturbance of nitric oxide metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Bagnato, Gianluca; Roberts, William Neal; Roman, Jesse; Gangemi, Sebastiano

    2017-06-30

    Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential. Copyright ©ERS 2017.

  10. Streptococcus pneumoniae bacteraemia due to parotitis in a patient with systemic sclerosis and secondary Sjögren's syndrome.

    Science.gov (United States)

    Yii, Irene Yuen Lin; Tan, Jamie Bee Xian; Fong, Warren Weng Seng

    2016-10-01

    Invasive pneumococcal disease is an uncommon and notifiable disease in Singapore. It is often associated with significant morbidity and mortality. We report a rare case of invasive pneumococcal bacteraemia due to parotitis in a patient with systemic sclerosis and secondary Sjögren's syndrome. We also present a retrospective review of Streptococcus pneumoniae bacteraemia cases in Singapore General Hospital from January 2011 to April 2016. A 59-year-old Malay lady with a history of systemic sclerosis with secondary Sjögren's syndrome presented with fever and left parotid gland swelling. Clinical examination revealed poor salivary pooling and left parotid swelling without fluctuance. Ultrasound of the left parotid gland confirmed acute parotitis without evidence of abscess or sialolithiasis. Blood cultures were positive for S. pneumoniae . She was diagnosed to have invasive pneumococcal bacteraemia secondary to acute parotitis, and treated with intravenous benzylpenicillin with clearance of bacteraemia after 3 days. Upon discharge, her antibiotics were changed to intravenous ceftriaxone to facilitate outpatient parenteral antibiotic therapy for another 2 weeks. She responded favourably to antibiotics at follow-up, with no complications from the bacteraemia. A review of the microbiological records of the Singapore General Hospital revealed 116 cases of pneumococcal bacteraemia, most (80.3 %) of which were due to pneumonia. None were due to parotitis. S. pneumoniae parotitis and subsequent bacteraemia is rare. Prompt recognition of the disease and appropriate use of antibiotics are important. This case highlights that close communication between healthcare workers (microbiologist, rheumatologist and infectious disease specialist) is essential in ensuring good clinical outcomes in patients with a potentially fatal disease.

  11. Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

    Science.gov (United States)

    Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

    2014-01-01

    Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These

  12. Amyotrophic lateral sclerosis mutant vesicle-associated membrane protein-associated protein-B transgenic mice develop TAR-DNA-binding protein-43 pathology.

    LENUS (Irish Health Repository)

    Tudor, E L

    2010-05-19

    Cytoplasmic ubiquitin-positive inclusions containing TAR-DNA-binding protein-43 (TDP-43) within motor neurons are the hallmark pathology of sporadic amyotrophic lateral sclerosis (ALS). TDP-43 is a nuclear protein and the mechanisms by which it becomes mislocalized and aggregated in ALS are not properly understood. A mutation in the vesicle-associated membrane protein-associated protein-B (VAPB) involving a proline to serine substitution at position 56 (VAPBP56S) is the cause of familial ALS type-8. To gain insight into the molecular mechanisms by which VAPBP56S induces disease, we created transgenic mice that express either wild-type VAPB (VAPBwt) or VAPBP56S in the nervous system. Analyses of both sets of mice revealed no overt motor phenotype nor alterations in survival. However, VAPBP56S but not VAPBwt transgenic mice develop cytoplasmic TDP-43 accumulations within spinal cord motor neurons that were first detected at 18 months of age. Our results suggest a link between abnormal VAPBP56S function and TDP-43 mislocalization.

  13. Recurrent meningitis associated with frontal sinus tuber encephalocele in a patient with tuberous sclerosis.

    Science.gov (United States)

    Elbabaa, Samer K; Riggs, Angela D; Saad, Ali G

    2011-07-01

    Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that commonly affects the CNS. The most commonly associated brain tumors include cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). The authors report an unusual case of recurrent meningitis due to a tuber-containing encephalocele via the posterior wall of the frontal sinus. An 11-year-old girl presented with a history of TSC and previous SEGA resection via interhemispheric approach. She presented twice within 4 months with classic bacterial meningitis. Cerebrospinal fluid cultures revealed Streptococcus pneumoniae. Computed tomography and MR imaging of the brain showed a right frontal sinus encephalocele via a posterior frontal sinus wall defect. Both episodes of meningitis were treated successfully with standard regimens of intravenous antibiotics. The neurosurgical service was consulted to discuss surgical options. Via a bicoronal incision, a right basal frontal craniotomy was performed. A large frontal encephalocele was encountered in the frontal sinus. The encephalocele was herniating through a bony defect of the posterior sinus wall. The encephalocele was ligated and resected followed by removing frontal sinus mucosa and complete cranialization of frontal sinus. Repair of the sinus floor was conducted with fat and pericranial grafts followed by CSF diversion via lumbar drain. Histopathology of the resected encephalocele showed a TSC tuber covered with respiratory (frontal sinus) mucosa. Tuber cells were diffusely positive for GFAP. The patient underwent follow-up for 2 years without evidence of recurrent meningitis or CSF rhinorrhea. This report demonstrates that frontal tubers of TSC can protrude into the frontal sinus as acquired encephaloceles and present with recurrent meningitis. To the authors' knowledge, recurrent meningitis is not known to coincide with TSC. Careful clinical and radiographic follow-up for frontal tubers in patients with TSC is

  14. Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

    Science.gov (United States)

    Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

    2018-01-01

    Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

  15. Does nailfold capillaroscopy help predict future outcomes in systemic sclerosis? A systematic literature review.

    Science.gov (United States)

    Paxton, Dolcie; Pauling, John D

    2018-02-14

    Nailfold capillaroscopy (NC) is an important diagnostic tool in systemic sclerosis (SSc). Confirmation of NC as a prognostic factor could facilitate earlier intervention and slow disease progression in SSc. We undertook a systematic literature review to evaluate the prognostic value of NC in predicting SSc disease progression. Standardised searches of EMBASE and MEDLINE were undertaken to identify longitudinal studies of adult subjects with SSc reporting the prognostic value of NC for any aspect of disease progression and/or survival. Non-English, non-original research, animal studies, non-adult studies and non-full length reports were excluded from the analysis (PROSPERO 2017:CRD42017071719). Wide heterogeneity in study design, prognostic factor measurement and study outcomes necessitated a qualitative data synthesis. The "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool was used to assess study quality. Study selection, data extraction and risk-of-bias assessment were each undertaken independently by 2 reviewers and consensus reached where necessary. Of 942 retrieved articles, 18 studies fulfilled the inclusion criteria. The majority of studies (17/18, 94%) reported positive associations between baseline NC appearances (using a variety of qualitative, semi-quantitative and quantitative NC endpoints) and clinical outcomes including digital ulcer (DU) occurrence/healing, survival, disease progression (using domains of Medsger disease severity scale), calcinosis, skin progression, pulmonary arterial hypertension (PAH), and/or a composite analysis of "cardiovascular events". Application of the QUIPS tool identified a moderate-high risk of potential bias in 6/18 studies for study participation, 3/18 studies for study attrition, 10/18 for prognostic factor measurement, 5/18 for outcome measurement, 13/18 for confounders and 13/18 for statistical analyses. Study quality limited the strength of the conclusions drawn from these studies. The most important source of

  16. Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis.

    Science.gov (United States)

    Caimmi, C; Caramaschi, P; Venturini, A; Bertoldo, E; Vantaggiato, E; Viapiana, O; Ferrari, M; Lippi, G; Frulloni, L; Rossini, M

    2018-04-01

    Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4-14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p = 0.007), lower physical activity (p = 0.028), longer disease duration (p = 0.019), worse predicted DLCO/VA and FVC (p = 0.009, respectively), worse disease severity according to Medsger severity score (p < 0.001), lower hemoglobin (p = 0.023), and fat-free mass (p < 0.001) and were more often sarcopenic (p < 0.001). In multivariate analysis, only FVC (p = 0.006) and disease severity (p = 0.003), in particular for the lungs (p = 0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\\140 patients (20.7%; 95% CI, 14.0-27.4%); 11\\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p = 0.049), worse DLCO/VA (p = 0.002), and lung (p = 0.006) and skin (p = 0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.

  17. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  18. Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status.

    Directory of Open Access Journals (Sweden)

    Michele D Binder

    2016-03-01

    Full Text Available Multiple Sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients.

  19. A wireless body measurement system to study fatigue in multiple sclerosis

    DEFF Research Database (Denmark)

    Yu, Fei; Rabotti, Chiara; Bilberg, Arne

    2012-01-01

    Fatigue is reported as the most common symptom by patients with multiple sclerosis (MS). The physiological and functional parameters related to fatigue in MS patients are currently not well established. A new wearable wireless body measurement system, named Fatigue Monitoring System (FAMOS......), was developed to study fatigue in MS. It can continuously measure electrocardiogram, body-skin temperature, electromyogram and motions of feet. The goal of this study is to test the ability of distinguishing fatigued MS patients from healthy subjects by the use of FAMOS. This paper presents the realization...... of the measurement system including the design of both hardware and dedicated signal processing algorithms. Twenty-six participants including 17 MS patients with fatigue and 9 sex- and age-matched healthy controls were included in the study for continuous 24 h monitoring. The preliminary results show significant...

  20. Radioimmunoassay determination of urinary prostaglandins in patients with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Ramirez P, P.; Erbessd, M.L.; Mares, G.; Recinos, G.; Graef S, A.; Lavalle, C.

    1985-01-01

    The results of urinary determinations of E-2 prostaglandines by radioimmunoassay (RIA) in 24-hour urine are presented for three groups: progressive systemic sclerotic patients with normotension and with elevated or normal APR, progressive systemic sclerotic patients with hypertension and with normal or low APR, control group of normal subjects. In a recent report of progressive systemic sclerosis in patients we demonstrated changes in the urine concentratrion of APR levels, sodium excretion and in total blood volume. Based on these findings we felt the need to perform quantifications of E-2 prostaglandines (PGE-2) in 24-hour recently taken urine samples stored at 70 0 and measure the sodium amounts excreted in the urine. We concluded that urinary determination of E-2 prostaglandines was the most suitable for our study as it allowed the establishment of relationships between APR, aldosterone and metabolic sodium balance. (author)

  1. The development of an MRI lesion quantifying system for multiple sclerosis patients undergoing treatment

    Science.gov (United States)

    Moin, Paymann; Ma, Kevin; Amezcua, Lilyana; Gertych, Arkadiusz; Liu, Brent

    2009-02-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that affects approximately 2.5 million people worldwide. Magnetic resonance imaging (MRI) is an established tool for the assessment of disease activity, progression and response to treatment. The progression of the disease is variable and requires routine follow-up imaging studies. Currently, MRI quantification of multiple sclerosis requires a manual approach to lesion measurement and yields an estimate of lesion volume and interval change. In the setting of several prior studies and a long treatment history, trends related to treatment change quickly become difficult to extrapolate. Our efforts seek to develop an imaging informatics based MS lesion computer aided detection (CAD) package to quantify and track MS lesions including lesion load, volume, and location. Together, with select clinical parameters, this data will be incorporated into an MS specific e- Folder to provide decision support to evaluate and assess treatment options for MS in a manner tailored specifically to an individual based on trends in MS presentation and progression.

  2. Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

    Science.gov (United States)

    Saigusa, Ryosuke; Asano, Yoshihide; Yamashita, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Sumida, Hayakazu; Tamaki, Zenshiro; Miyazaki, Miki; Yoshizaki, Ayumi; Sato, Shinichi

    2018-03-01

    Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  3. In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

    International Nuclear Information System (INIS)

    Martin, Abraham; Szczupak, Boguslaw; Arrieta, Ander; Vazquez-Villoldo, Nuria; Soria, Federico N.; Domercq, Maria; Matute, Carlos; Gomez-Vallejo, Vanessa; Llop, Jordi; Padro, Daniel; Plaza-Garcia, Sandra; Reese, Torsten

    2016-01-01

    Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc - activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown. Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[ 18 F]Fluoro-2-deoxy-D-glucose ([ 18 F]FDG), [ 11 C]-(R)-1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl) -3-isoquinolinecarbox amide ([ 11 C]PK11195) and (4S)-4-(3- 18 F-fluoropropyl)-L-glutamate ([ 18 F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats. [ 18 F]FSPG showed a significant increase of system xc - function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [ 18 F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [ 11 C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [ 18 F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [ 18 F]FDG and [ 11 C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [ 18 F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats. Altogether, these results suggest that in vivo PET imaging of system xc - could become a valuable tool for the diagnosis and treatment evaluation of MS. (orig.)

  4. Speech and Pause Characteristics Associated with Voluntary Rate Reduction in Parkinson's Disease and Multiple Sclerosis

    Science.gov (United States)

    Tjaden, Kris; Wilding, Greg

    2011-01-01

    The primary purpose of this study was to investigate how speakers with Parkinson's disease (PD) and Multiple Sclerosis (MS) accomplish voluntary reductions in speech rate. A group of talkers with no history of neurological disease was included for comparison. This study was motivated by the idea that knowledge of how speakers with dysarthria…

  5. IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

    Science.gov (United States)

    Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

    2009-01-01

    Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

  6. Distinct evolution of TLR-mediated dendritic cell cytokine secretion in patients with limited and diffuse cutaneous systemic sclerosis.

    NARCIS (Netherlands)

    Bon, L. van; Popa, C.; Huibens, R.J.F.; Vonk, M.C.; York, M.; Simms, R.; Hesselstrand, R.; Wuttge, D.M.; Lafyatis, R.; Radstake, T.R.D.J.

    2010-01-01

    BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease and accumulating evidence suggests a role for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). OBJECTIVE: To map TLR-mediated cytokine responses of DCs from patients with SSc. METHODS: 45 patients with SSc were

  7. Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Trebst, Corinna; Kivisäkk, Pia

    2002-01-01

    T-cell accumulation in the central nervous system (CNS) is considered crucial to the pathogenesis of multiple sclerosis (MS). We found that the majority of T cells within the cerebrospinal fluid (CSF) compartment expressed the CXC chemokine receptor 3 (CXCR), independent of CNS inflammation...

  8. Influence of clinical features, serum antinuclear antibodies, and lung function on survival of patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Ullman, S; Shen, G Q

    2001-01-01

    OBJECTIVE: To evaluate the independent contribution of several clinical and laboratory variables to the mortality of a cohort of Danish patients with systemic sclerosis (SSc). METHODS: A cohort of 174 patients with incident SSc was retrospectively identified using clinical charts and study record...

  9. Auto-anticorpos na Esclerose Sistêmica (ES Autoantibody in the Systemic Sclerosis (SS

    Directory of Open Access Journals (Sweden)

    Luís Eduardo Coelho Andrade

    2004-06-01

    Full Text Available A esclerose sistêmica (ES é uma enfermidade inflamatória crônica idiopática, cujo principal indício de vínculo com a auto-imunidade é a presença de auto-anticorpos na maior parte dos pacientes. Pelo teste de imunofluorescência indireta em células HEp-2, observa-se reatividade predominantemente contra o nucléolo e o núcleo, sendo que títulos de anticorpos antinucléolo acima de 1/640 são fortemente sugestivos de ES. Alguns desses auto-anticorpos apresentam alta especificidade para a ES, sendo considerados marcadores diagnósticos dessa enfermidade. São exemplos os anticorpos anti-Scl-70, antifibrilarina e anti-RNA polimerase I. Outros apresentam interessantes associações com manifestações específicas da ES, como os anticorpos anticentrômero, associados às formas limitadas, os anticorpos anti-RNA polimerase III, associados ao extenso comprometimento da pele, e os anticorpos anti-To/Th, associados às formas limitadas com propensão ao desenvolvimento de hipertensão pulmonar. Algumas dessas associações estão bem estabelecidas em diversos estudos, de diferentes grupos de pesquisadores. Outras, entretanto, devem ser vistas com cautela, pois a exigüidade de casos disponíveis para estudo pode ensejar conclusões preliminares e não acuradas. A detecção de anticorpos anticentrômero por técnica de IFI e anti-Scl-70 por imunodifusão dupla ou por ELISA está disponível nos principais laboratórios clínicos capacitados na área de auto-imunidade. O mesmo não se aplica para a maior parte dos demais auto-anticorpos associados à ES. Espera-se que, com a implementação rotineira de técnicas para detecção desses outros auto-anticorpos, o real significado clínico dos mesmos venha a ser melhor conhecido.Systemic Sclerosis (SS is a chronic idiopathic inflammatory disease whose main hint towards autoimmunity is given by the presence of high serum levels of autoantibodies in the majority of the patients. In indirect

  10. Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis.

    Science.gov (United States)

    Xu, Yang; Wang, Wenling; Tian, Yanli; Liu, Jingyang; Yang, Rongya

    2016-04-01

    Systemic sclerosis (SSc) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SSc. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 (STAT4) rs7574865 and interferon regulatory factor 5 (IRF5) rs2004640 polymorphisms with risk of SSc. Case-control studies were obtained from the electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) up to December 2013. The association between STAT4 and IRF5 polymorphisms and SSc susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CI). Six related studies, including 4746 SSc cases and 7399 healthy controls, were pooled in this meta-analysis. For STAT4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SSc susceptibility (OR = 1.37, 95% CI = 1.27-1.48, P rs7574865 and IRF5 rs2004640G/T substitution are associated with a susceptibility to SSc, and they may serve as the SSc genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SSc and have provided new insight into the pathogenesis of SSc. © 2015 The International Society of Dermatology.

  11. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis

    DEFF Research Database (Denmark)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Fredriksen, Jette Lautrup

    2016-01-01

    Background Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis...... associated with Interferon-beta treatment. Case presentation We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved...... Interferon-beta-1-alpha therapy in patients with multiple sclerosis....

  12. Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.

    Science.gov (United States)

    Maria, Alexandre T J; Toupet, Karine; Maumus, Marie; Fonteneau, Guillaume; Le Quellec, Alain; Jorgensen, Christian; Guilpain, Philippe; Noël, Danièle

    2016-06-01

    Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. December insolation and ultraviolet B radiation are associated with multiple sclerosis mortality in Poland

    Directory of Open Access Journals (Sweden)

    Wojciech Cendrowski

    2013-06-01

    Full Text Available Background: The role of environmental factors (EF determining the occurrence of multiple sclerosis (SM is the subject of current investigations. Objective: To establish association between duration of insolation along with intensity of ultraviolet B (UVB radiation and mortality rates for SM in Poland. Method: The study was based on assemblage of 2172 SM persons (M – 878, F – 1294 who died in Poland in the years 2004–2008. Regional previous duration of insolation was measured in hours, intensity of UVB radiation was monitored in minimal erythema dose units (MED, ozone concentration in the ground layer of atmosphere was recorded in µg/m3 . Measurements of insolation, UVB radiation and ozone concentration were performed at provincial stations and territorial sites of the State Environmental Monitoring. EF were correlated to provincial crude mortality rates (CMR for MS. Correlational test by Pearson was used in the study. Demographic data were obtained from the Central Statistical Office, information on EF was received from the Institute of Meteorology and the Institute of Environmental Protection. Results: Annual, average, crude MR for MS per 100,000 inhabitants in Poland was 1.12 (SD 0.14. In northern part it amounted to 1.20 (SD 0.18 and in southern part reached 1.03 (SD 0.11. Significant inverse correlation was found between previous minimal duration of insolation in December and CMR for SM in the country: r = -0.518, p = 0.044. Borderline significance of inverse correlation was established between minimal intensity of UVB radiation in December and crude death rates for SM in Poland: r = -0.478, p = 0.060. CMR for SM in northern Poland was accompanied not only by lower UVB radiation level, but also by slower spring increase and autumn faster decrease of radiation. No significant correlation was ascertained between the ground atmospheric ozone concentration or the annual number of days with ozone concentration above 120 µg/m3 and MS

  14. Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

    NARCIS (Netherlands)

    van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

    2010-01-01

    A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

  15. Isolated pulmonary veno-occlusive disease and pulmonary arterial thrombosis in systemic sclerosis – a lethal combination

    Directory of Open Access Journals (Sweden)

    Arun Jeevagan

    2010-05-01

    Full Text Available Arun JeevaganGeneral Medicine, Ipswich NHS Hospital, UKBackground: Isolated pulmonary hypertension secondary to systemic sclerosis is not uncommon. Our patient with systemic sclerosis presented with a very aggressive form of pulmonary hypertension due to a lethal combination of pulmonary veno-occlusive disease (PVOD and pulmonary arterial thrombosis. This combined presentation has never before been reported in medical literature.Case report: A 75-year-old woman with a 4-month history of atypical chest pains was admitted with a 3-week history of worsening symptoms of shortness of breath, reduced exercise tolerance, and bilateral pitting edema. On examination she had thickened skin in her hands, telangiectasia on her face, maculopapular rash in her legs, raised jugular venous pressure, and bilateral pitting edema. Her autoimmune profile revealed positive anticentromere antibodies, and her echocardiogram showed right ventricular systolic pressure of 91 mmHg. She also had renal impairment secondary to hypoperfusion. A diagnosis of isolated pulmonary hypertension secondary to limited systemic sclerosis was made. As she was clinically improving on slow diuretic infusion and awaiting transfer to a specialist center for management of pulmonary hypertension, our patient died due to cardiopulmonary arrest. Her postmortem revealed that she died of a combination of PVOD and pulmonary arteriopathy due to thrombosis.Conclusion: This is clearly a unique case both in presentation and difficulty of management. Pulmonary vasodilators used in therapy of pulmonary arteriopathy can be detrimental in patients with PVOD. There is no definitive investigation, curative treatment, or management, that exists for a combination of PVOD and pulmonary arteriopathy due to thrombosis secondary to systemic sclerosis.Keywords: pulmonary veno-occlusive disease, pulmonary arterial hypertension, systemic sclerosis, pulmonary arteriopathy with thrombosis

  16. T Helper Cells in the Immunopathogenesis of Systemic Sclerosis – Current Trends

    Directory of Open Access Journals (Sweden)

    Krasimirova E.

    2017-05-01

    Full Text Available Systemic sclerosis (SSc is a chronic progressive autoimmune disease characterized by skin and multiorgan involvement with alterations in both the innate and adaptive immunities. The hallmark of the disease is widespread fibrosis engaging the skin and multiple internal organs, as well as the musculoskeletal system. There is mounting evidence that T cells are key players in the pathogenesis of scleroderma. The current review discusses the role of the different T helper (Th lymphocyte subsets in the processes of inflammation and fibrosis, characteristics for the pathogenesis of the disease. Cytokines produced by Th cell populations have a major effect on endothelial cells and fibroblasts in the context of favoring/inhibiting the vasculopathy and the fibrosis spread. The Th2 pro-fibrotic cytokines IL-4 and IL-13 have been shown to induce collagen synthesis by fibroblasts, whereas IFN-γ demonstrates an inhibitory effect. Increased Th17 cells are present in the scleroderma skin infiltrates. The combination of IL-17, IFN-γ and TGF-β levels in CD45RO and CD45RA cells from patients with SSc is useful to distinguish between the limited and the diffuse phenotype of the disease. There are accumulating data for functional and numerical alterations in the Tregs in SSc. High levels of TNF-α which might reduce the suppressive ability of Tregs have been described. According to some studies, the number of Tregs in scleroderma skin biopsies has been decreased against the normal absolute number of Tregs in peripheral blood of the same patients, which suggests suppressed immunomodulatory response. Other studies reported increased frequency of Tregs in peripheral blood of patients with systemic sclerosis and established a correlation with disease activity. The main immunological challenge remains the identification of the trigger of the autoimmune response in SSc, the causes for preferential Th2-type cell responses and the immunological differences between the

  17. A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis.

    Science.gov (United States)

    Colpitts, Sara L; Kasper, Eli J; Keever, Abigail; Liljenberg, Caleb; Kirby, Trevor; Magori, Krisztian; Kasper, Lloyd H; Ochoa-Repáraz, Javier

    2017-11-02

    The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS). This non-obese diabetic (NOD) model of EAE develops a biphasic pattern of disease that more closely resembles the human condition when transitioning from relapsing-remitting (RR)-MS to SP-MS. We compared the gut microbiome of NOD mice with either mild or severe disease to that of non-immunized control mice. We found that the mice which developed a severe secondary form of EAE harbored a dysbiotic gut microbiome when compared with the healthy control mice. Furthermore, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics would modify the outcome of the progressive stage of EAE in the NOD model. Our results indicated reduced mortality and clinical disease severity in mice treated with antibiotics compared with untreated mice. Our findings support the hypothesis that there are reciprocal effects between experimental CNS inflammatory demyelination and modification of the microbiome providing a foundation for the establishment of early therapeutic interventions targeting the gut microbiome that could potentially limit disease progression.

  18. Envolvimento macrovascular e esclerose sistêmica Macrovascular involvement and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Emmanuelle Tenório Albuquerque Madruga Godoi

    2009-03-01

    .The objectives of this article are to review aspects described in the literature on macrovasculature onset in systemic sclerosis and to assess occurrence and distribution of macrovascular alterations in patients with systemic sclerosis using Doppler ultrasound and ankle-brachial index. In addition, the article evaluates the association of these findings with demographic characteristics, clinical form, clinical course of the disease, Raynauds phenomenon, digital changes, limb ulcers, reabsorption of phalanges, amputation, and risk factors and antecedents of atheromatous disease. A prospective, case series study of 20 patients was performed. The sample was comprised of 19 women, with a mean age of 46.30 years. All patients had objective Raynauds phenomenon, 85% were diffuse, 55% had digital pulp changes, 15% current limb ulcer, 25% reabsorption of phalange, no amputations, and 70% presented one to four risk factors. Studies were performed by color Doppler ultrasound of the aortic and carotid arteries and lower and upper limb arteries to assess thickening of the intima-media complex, presence of plaques and aneurysms. Ankle-brachial index was also performed in lower limb arteries. Ankle-brachial index was normal in all patients, but 12 (60% had macrovascular disease assessed by Doppler ultrasound, nine (45% of these in the aorta, six (30% in the carotid arteries, one (5% in the upper limb arteries, and seven (35% in lower limb arteries. There was an association between macrovascular disease and digital pulp changes (p = 0.0045. Macrovascular disease was identified in 60% of the patients via Doppler ultrasound, but not via ankle-brachial index, which resulted normal in all patients. There was a significant association between macrovascular disease and current digital pulp changes, which did not occur with the other variables.

  19. Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients.

    Science.gov (United States)

    Ruaro, B; Sulli, A; Pizzorni, C; Paolino, S; Smith, V; Cutolo, M

    2016-05-01

    To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (pnailfold capillaroscopy scores of microangiopathy. Copyright © 2016. Published by Elsevier Inc.

  20. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality

    DEFF Research Database (Denmark)

    Thormann, Anja; Sorensen, Per Soelberg; Koch-Henriksen, Nils

    2017-01-01

    Objective: To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS. Methods: We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005. To inve......Objective: To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS. Methods: We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005.......007). Conclusions: An increased awareness of both the necessity of neurologic evaluation of new neurologic symptoms in persons with preexisting chronic disease and of optimum treatment of comorbidity in MS is critical....

  1. Generalized morphea, lichen sclerosis et atrophicus associated with oral submucosal fibrosis in an adult male

    Directory of Open Access Journals (Sweden)

    Virdi Sarvjit

    2009-01-01

    Full Text Available Generalized morphea is a disease characterized by wide-spread sclerosis of the skin. A 39-year-old man presented with history of multiple pigmented and bound-down plaques on the body along with mucosal involvement. Dermatological examination showed multiple indurated and sclerosed plaques with follicular plugging in few of them and gross thickened eroded and glazed tongue. The constellation of these findings with histopathological correlation led us to diagnosis of this spectrum of cutaneous involvement. The coexistence of localized morphea with lichen sclerosis et atrophicus has been reported earlier but existence of these entities with submucosal fibrosis in a same patient is documented here and is the first of its kind.

  2. Desmoplastic Fibroma Recurrence Associated with Tuberous Sclerosis in a Young Patient

    Directory of Open Access Journals (Sweden)

    A. M. Espinoza-Coronado

    2018-01-01

    Full Text Available Case Report. A nine-year-old patient with a diagnosis of tuberous sclerosis (with no pathological record that showed calcifications at the brain level. Besides, the case showed the Vogt triad (epilepsy, mental retardation, and sebaceous adenoma. The patient clinically showed a volume increase of hard consistency, without suppuration and no sessile that included the following teeth 73, 74, and 75. Cone beam computed tomography (CBCT was obtained, and it displayed a delimited unilocular lesion. After surgical excision, the histopathological report was desmoplastic fibroma (DF. It was observed that the patient had an aggressive recurrence of DF at four months after surgery treatment. Due to these clinical findings, resective osseous surgery and curettage were carried out. It is uncommon to find these two pathologies together (DF and tuberous sclerosis. Since DF is a benign pathology but very invasive and destructive, it is necessary a constant follow-up examination due to a high recurrence frequency.

  3. High fat diet exacerbates neuroinflammation in an animal model of multiple sclerosis by activation of the Renin Angiotensin system.

    Science.gov (United States)

    Timmermans, Silke; Bogie, Jeroen F J; Vanmierlo, Tim; Lütjohann, Dieter; Stinissen, Piet; Hellings, Niels; Hendriks, Jerome J A

    2014-03-01

    Epidemiological studies suggest a positive correlation between the incidence and severity of multiple sclerosis (MS) and the intake of fatty acids. It remains to be clarified whether high fat diet (HFD) indeed can exacerbate the disease pathology associated with MS and what the underlying mechanisms are. In this study, we determined the influence of HFD on the severity and pathology of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Mice were fed either normal diet (ND) or HFD and subsequently induced with EAE. Immunohistochemical staining and real-time PCR were used to determine immune cell infiltration and inflammatory mediators in the central nervous system (CNS). Our data show that HFD increases immune cell infiltration and inflammatory mediator production in the CNS and thereby aggravates EAE. Moreover, our data demonstrate that activation of the renin angiotensin system (RAS) is associated with the HFD-mediated effects on EAE severity. These results show that HFD exacerbates an autoreactive immune response within the CNS. This indicates that diets containing excess fat have a significant influence on neuroinflammation in EAE, which may have important implications for the treatment and prevention of neuroinflammatory disorders.

  4. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    Science.gov (United States)

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  5. Associations between proprioceptive neural pathway structural connectivity and balance in people with multiple sclerosis

    OpenAIRE

    Brett W Fling; Brett W Fling; Geetanjali eGera-Dutta; Heather eSchlueter; Michelle H Cameron; Michelle H Cameron; Fay B Horak; Fay B Horak

    2014-01-01

    Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance dis...

  6. Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis

    OpenAIRE

    Fling, Brett W.; Dutta, Geetanjali Gera; Schlueter, Heather; Cameron, Michelle H.; Horak, Fay B.

    2014-01-01

    Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance dis...

  7. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Ninaber, Maarten K., E-mail: m.k.ninaber@lumc.nl [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Stolk, Jan; Smit, Jasper; Le Roy, Ernest J. [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Kroft, Lucia J.M. [Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Els Bakker, M. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Vries Bouwstra, Jeska K. de; Schouffoer, Anne A. [Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Staring, Marius; Stoel, Berend C. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands)

    2015-05-15

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  8. Workplace barriers encountered by employed persons with systemic sclerosis.

    Science.gov (United States)

    Poole, Janet L; Anwar, Sahar; Mendelson, Cindy; Allaire, Saralynn

    2016-01-01

    Systemic sclerosis (SSc) is an auto-immune connective tissue disease characterized by fibrosis of skin, blood vessels, and internal organs that results in significant disability. To identify the work barriers faced by people with systemic sclerosis (SSc) in maintaining employment. Thirty-six people with SSc who were working more than 8 hours per week completed the Work Experience Survey, which contains lists of potential work barriers, including the ability to travel to and from work; get around at work; perform essential job functions, including physical, cognitive, and task-related activities; work with others; and manage work conditions. Thirty-three participants completed and returned the questionnaires, most of whom were female, and working full time and in professional careers. Principal disease symptoms included fatigue, Raynaud's phenomenon, esophageal involvement, and leg or hand/wrist pain. All participants reported some barriers with a mean of 18 barriers per participant. At least three quarters of participants cited outside temperature (82%), cold temperatures inside the workplace (76%), and household work (76%), as barriers. The next most common barriers were using both hands (64%), arranging and taking part in social activities (64%), being able to provide self-care (61%) and working 8 hours (58%). Participants reported a wide range of barriers, from cold temperatures, to physical job, fatigue related, and non-workplace demands, in maintaining the worker role. The barriers reflect the disease symptoms they reported. Identifying workplace barriers facilitates the creation of job accommodations or adaptations that will allow people with SSc to continue working.

  9. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    International Nuclear Information System (INIS)

    Ninaber, Maarten K.; Stolk, Jan; Smit, Jasper; Le Roy, Ernest J.; Kroft, Lucia J.M.; Els Bakker, M.; Vries Bouwstra, Jeska K. de; Schouffoer, Anne A.; Staring, Marius; Stoel, Berend C.

    2015-01-01

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  10. Tuberous sclerosis complex: Recent advances in manifestations and therapy.

    Science.gov (United States)

    Wataya-Kaneda, Mari; Uemura, Motohide; Fujita, Kazutoshi; Hirata, Haruhiko; Osuga, Keigo; Kagitani-Shimono, Kuriko; Nonomura, Norio

    2017-09-01

    Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, "a cross-sectional medical examination system," a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex. © 2017 The Japanese Urological Association.

  11. STRUCTURAL AND FUNCTIONAL CHANGES EVALUATED BY ECHOCARDIOGRAPHY IN PATIENTS WITH SYSTEMIC SCLEROSIS AND HEART RATE VARIABILITY

    Directory of Open Access Journals (Sweden)

    E. O. Saad

    2017-01-01

    Full Text Available Objective: to estimate heart rate variability (HRV in patients with systemic sclerosis (SS and to investigate their relationship to echocardiographic structural and functional changes in the heart.Subjects and methods. The investigation enrolled 125 patients with SS and 50 gender- and age-matched apparently healthy individuals who made up a control group. In addition to clinical examinations, 73 patients underwent HRV assessment from 24-hour Holter electrocardiogram (ECG monitoring results and 121 patients had echocardiography (EchoCG. 24-hour Holter ECG monitoring was carried out in all control individuals.Results and discussion. Examination of the main parameters of time-domain HRV in patients with SS revealed a significant decline in all temporal and spectral indices, except for the mean R–R interval duration (meanNN, as compared with the control group. EchoCG detected a variety of changes, primarily the induration and calcification of aortic and mitral valves in most patients. Left ventricular diastolic dysfunction was encountered in almost half of the patients with SS. Eight patients had a lower left ventricular ejection fraction (LVEF, which was <55%. Studying the association of HRV values with separate EchoCG parameters revealed significant inverse correlations of the mean standard deviation of R–R intervals in 5-minute recording segments during 24 hours with the thickness of the interventricular septum (r = -0.18; p < 0.05 and with the induration of the aortic valve (r = -0.18; p < 0.05; the square root mean squared of successive differences (RMSSD, ms for R–R intervals and the percentage of adjacent R–R intervals that varied by more than 50 ms (pNN50 correlated with the induration of the aortic valve (r = -0.23; p<0.05 and r = -0.25; p < 0.05, respectively, with the presence of pericarditis (r = -0.24; p < 0.05 and r = -0,27; p < 0.05, respectively, and with the level of pulmonary artery systolic pressure (r = -0

  12. Survival and causes of death in systemic sclerosis patients: a single center registry report from Iran.

    Science.gov (United States)

    Poormoghim, Hadi; Andalib, Elham; Jalali, Arash; Ghaderi, Afshin; Ghorbannia, Ali; Mojtabavi, Nazanin

    2016-07-01

    The aims of the study were to determine prognostic factors for survival and causes of death in a cohort of patients with systemic sclerosis (SSc). This was a cohort study of SSc patients in single rheumatologic center from January 1998 to August 2012. They fulfilled the American College of Rheumatology classification criteria for SSc or had calcinosis Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia or sine sclerosis. Causes of death were classified as SSc related and non-SSc related. Kaplan-Meier and Cox proportional hazard regression models were used in univariate and multivariate analysis to analyse survival in subgroups and determine prognostic factors of survival. The study includes 220 patients (192 female, 28 male). Out of thirty-two (14.5 %) who died, seventeen (53.1 %) deaths were SSc related and in nine (28.1 %) non-SSc-related causes, and in six (18.8 %) of patients causes of death were not defined. Overall survival rate was 92.6 % (95 % CI 87.5-95.7 %) after 5 years and 82.3 % (95 % CI 73.4-88.4 %) after 10 years. Pulmonary involvement was a major SSc-related cause of death, occurred in seven (41.1 %) patients. Cardiovascular events were leading cause of in overall death (11) 34.3 % and 6 in non-SSc-related death. Independent risk factors for mortality were age >50 at diagnosis (HR 5.10) advance pulmonary fibrosis (HR 11.5), tendon friction rub at entry (HR 6.39), arthritis (HR 3.56). In this first Middle Eastern series of SSc registry, pulmonary and cardiac involvements were the leading cause of SSc-related death.

  13. Cortical injury in multiple sclerosis; the role of the immune system

    Directory of Open Access Journals (Sweden)

    Walker Caroline A

    2011-12-01

    Full Text Available Abstract The easily identifiable, ubiquitous demyelination and neuronal damage that occurs within the cerebral white matter of patients with multiple sclerosis (MS has been the subject of extensive study. Accordingly, MS has historically been described as a disease of the white matter. Recently, the cerebral cortex (gray matter of patients with MS has been recognized as an additional and major site of disease pathogenesis. This acknowledgement of cortical tissue damage is due, in part, to more powerful MRI that allows detection of such injury and to focused neuropathology-based investigations. Cortical tissue damage has been associated with inflammation that is less pronounced to that which is associated with damage in the white matter. There is, however, emerging evidence that suggests cortical damage can be closely associated with robust inflammation not only in the parenchyma, but also in the neighboring meninges. This manuscript will highlight the current knowledge of inflammation associated with cortical tissue injury. Historical literature along with contemporary work that focuses on both the absence and presence of inflammation in the cerebral cortex and in the cerebral meninges will be reviewed.

  14. Comprometimento pulmonar na esclerose sistêmica: revisão de casos Pulmonary involvement in systemic sclerosis: cases review

    Directory of Open Access Journals (Sweden)

    Marcel Koenigkam Santos

    2006-06-01

    Full Text Available OBJETIVO: Rever e avaliar os padrões de alterações encontrados em exames de imagem de pacientes com comprometimento pulmonar da esclerose sistêmica. MATERIAIS E MÉTODOS: Foram retrospectivamente estudados os exames de radiografia simples e tomografia computadorizada de alta resolução de 23 pacientes com esclerose sistêmica. RESULTADOS: Na radiografia simples, o padrão reticular em bases pulmonares foi predominante, tendo sido verificado em 18 pacientes (78,2%. A tomografia computadorizada de alta resolução evidenciou lesão pulmonar em todos os pacientes estudados, encontrando-se faveolamento em nove pacientes (39,1%, opacidades em vidro fosco associadas a opacidades reticulares em oito (34,7%, predomínio de opacidades reticulares em cinco (21,7% e vidro fosco em um paciente (4,3%. CONCLUSÃO: O padrão de anormalidades tomográficas possui boa correlação com os achados histopatológicos, diferenciando padrões predominantemente inflamatórios de fibróticos, com os padrões inflamatórios estando associados a uma resposta superior ao tratamento. Dessa maneira, observou-se alteração sugestiva de fibrose na maior parte dos casos (faveolamento e opacidades reticulares somando 60,8%, porém com boa parte apresentando padrões sugestivos de processo inflamatório.OBJECTIVE: To review and evaluate the patterns of imaging examinations findings of lung disease in patients with systemic sclerosis. MATERIALS AND METHODS: Plain x-rays and high-resolution computed tomography studies of 23 patients with systemic sclerosis were retrospectively analyzed. RESULTS: At plain x-rays, pulmonary disease with reticular pattern had higher prevalence, appearing in 18 patients (78.2%. High-resolution computed tomography showed lung involvement in the whole group of patients, with honeycombing in nine patients (39.1%, ground-glass opacities associated with reticular opacities in eight patients (34.7%, predominance of reticular opacities in five (21

  15. Rehabilitation and multiple sclerosis

    DEFF Research Database (Denmark)

    Dalgas, Ulrik

    2011-01-01

    In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

  16. Shift work at young age is associated with increased risk of multiple sclerosis in a Danish population.

    Science.gov (United States)

    Gustavsen, S; Søndergaard, H B; Oturai, D B; Laursen, B; Laursen, J H; Magyari, M; Ullum, H; Larsen, M H; Sellebjerg, F; Oturai, A B

    2016-09-01

    Epidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15-19 years. The aim of this study was to investigate the association between shift work at young age and the risk of developing MS. We performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15-19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors. We found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08-1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01-1.06, p=0.002). Duration of shift work in years was not associated with risk of MS. This study supports a statistically significant association between shift work at age 15-19 years and MS risk. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Abraham; Szczupak, Boguslaw; Arrieta, Ander [CIC biomaGUNE, Molecular Imaging Unit, San Sebastian (Spain); Vazquez-Villoldo, Nuria; Soria, Federico N.; Domercq, Maria; Matute, Carlos [University of the Basque Country, Department of Neurosciences, Leioa (Spain); UPV/EHU, Achucarro Basque Center for Neuroscience, Zamudio (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Leioa (Spain); Gomez-Vallejo, Vanessa; Llop, Jordi [CIC biomaGUNE, Molecular Imaging Unit, San Sebastian (Spain); CIC biomaGUNE, Radiochemistry and Nuclear Imaging, San Sebastian (Spain); Padro, Daniel; Plaza-Garcia, Sandra; Reese, Torsten [CIC biomaGUNE, Molecular Imaging Unit, San Sebastian (Spain); CIC biomaGUNE, Magnetic Resonance Imaging, San Sebastian (Spain)

    2016-06-15

    Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc{sup -} activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown. Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[{sup 18}F]Fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG), [{sup 11}C]-(R)-1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl) -3-isoquinolinecarbox amide ([{sup 11}C]PK11195) and (4S)-4-(3-{sup 18}F-fluoropropyl)-L-glutamate ([{sup 18}F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats. [{sup 18}F]FSPG showed a significant increase of system xc{sup -} function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [{sup 18}F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [{sup 11}C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [{sup 18}F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [{sup 18}F]FDG and [{sup 11}C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [{sup 18}F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats. Altogether, these results suggest that in vivo PET imaging of system xc{sup -} could become a valuable tool for the diagnosis and treatment evaluation of MS. (orig.)

  18. Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

    Science.gov (United States)

    Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

    2013-04-01

    Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

  19. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

    Directory of Open Access Journals (Sweden)

    Fuencisla Matesanz

    Full Text Available Multiple Sclerosis (MS is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9. This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

  20. Chronic comorbidity in multiple sclerosis is associated with lower incomes and dissolved intimate relationships

    DEFF Research Database (Denmark)

    Thormann, A.; Sorensen, P. S.; Koch-Henriksen, N.

    2017-01-01

    at MS onset or who entered a relationship after MS onset. We used logistic, multiple linear and Poisson regression analyses. Results: Cases of MS with somatic comorbidity had increased odds of low incomes both 5 years {odds ratio (OR), 1.41 [95% confidence interval (CI), 1.19–1.67; P ...Background and purpose: The social and economic consequences of comorbidity in multiple sclerosis (MS) are largely unexplored. Differences were investigated in income and in the rate of broken relationships between cases of MS with and without chronic comorbidity. Methods: We conducted a nationwide...

  1. [Evaluation of the equilibrium system in patients with multiple sclerosis based on qualitative assessment with videonystagmography].

    Science.gov (United States)

    Kenig, Dagmara; Kantor, Ireneusz; Jurkiewicz, Dariusz

    2005-09-01

    Multiple sclerosis (SM) is the most frequent inflammatory-demyelinating disease of central nervous system. The character of SM disease provokes that its most frequent symptoms are vertigo, equilibrium disorders and ataxia. Objective method of vertigo estimation is evaluation of the nystagmus via videonystagmography registration (VNG). This examination allows to simultaneously assess the vertical and horizontal component of the nystagmus. It is considered that mainly the vertical nystagmus is characteristic to equilibrium system impairments of the central nervous system, caused also by SM. The study was carried out on 40 patients (28 women, 12 men) with SM diagnosed as a result of neurological examination. 7 patients (17.5%) suffered from sham - movement vertigo, while 33 patients (82.5%) suffered from instability of posture and walking deviation. The videonystagmography examination resulted in the following: deviation of the eye movement was recorded in 26 patients (65%) during either in saccadic test and in smooth pursuit test, optokinetic nystagmus recorded: dissymetric and variable amplitude result in 24 patients (60%), presence of vertical nystagmus component in 30 patients (75%), positional test: directional-changable nystagmus in 8 patients (20%), pendular nystagmus in 4 patients (10%), presence of vertical nystagmus component in 31 patients (77.5%), caloric test: impairments of one of the labyrinth recorded in 12 patients (30%). SM is still the diagnostic and therapeutic problem. During the mentioned tests we have found the quantitative and qualitative changes in VNG recordings. This may be helpful in SM diagnosis, mainly during its early stages.

  2. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Es, M.A. van; Veldink, J.H.; Saris, C.G.J.; Blauw, H.M.; Vught, P.W. van; Birve, A.; Lemmens, R.; Schelhaas, H.J.; Groen, E.J.; Huisman, M.H.; Kooi, A.J. van der; Visser, M. de; Dahlberg, C.; Estrada, K.; Rivadeneira, F.; Hofman, A.; Zwarts, M.J.; Doormaal, P.T. van; Rujescu, D.; Strengman, E.; Giegling, I.; Muglia, P.; Tomik, B.; Slowik, A.; Uitterlinden, A.G.; Hendrich, C.; Waibel, S.; Meyer, T.; Ludolph, A.C.; Glass, J.D.; Purcell, S.; Cichon, S.; Nothen, Markus; Wichmann, H.E.; Schreiber, S.; Vermeulen, S.; Kiemeney, L.A.L.M.; Wokke, J.H.J.; Cronin, S.; McLaughlin, R.L.; Hardiman, O.; Fumoto, K.; Pasterkamp, R.J.; Meininger, V.; Melki, J.; Leigh, P.N.; Shaw, C.E.; Landers, J.E.; Al-Chalabi, A.; Brown Jr., R.H.; Robberecht, W.; Andersen, P.M.; Ophoff, R.A.; Berg, L.H. van den

    2009-01-01

    We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide

  3. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Es, Michael A.; Veldink, Jan H.; Saris, Christiaan G. J.; Blauw, Hylke M.; van Vught, Paul W. J.; Birve, Anna; Lemmens, Robin; Schelhaas, Helenius J.; Groen, Ewout J. N.; Huisman, Mark H. B.; van der Kooi, Anneke J.; de Visser, Marianne; Dahlberg, Caroline; Estrada, Karol; Rivadeneira, Fernando; Hofman, Albert; Zwarts, Machiel J.; van Doormaal, Perry T. C.; Rujescu, Dan; Strengman, Eric; Giegling, Ina; Muglia, Pierandrea; Tomik, Barbara; Slowik, Agnieszka; Uitterlinden, Andre G.; Hendrich, Corinna; Waibel, Stefan; Meyer, Thomas; Ludolph, Albert C.; Glass, Jonathan D.; Purcell, Shaun; Cichon, Sven; Nöthen, Markus M.; Wichmann, H.-Erich; Schreiber, Stefan; Vermeulen, Sita H. H. M.; Kiemeney, Lambertus A.; Wokke, John H. J.; Cronin, Simon; McLaughlin, Russell L.; Hardiman, Orla; Fumoto, Katsumi; Pasterkamp, R. Jeroen; Meininger, Vincent; Melki, Judith; Leigh, P. Nigel; Shaw, Christopher E.; Landers, John E.; Al-Chalabi, Ammar; Brown, Robert H.; Robberecht, Wim; Andersen, Peter M.; Ophoff, Roel A.; van den Berg, Leonard H.

    2009-01-01

    We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P <1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide

  4. Clinical and diagnostic significance of activity of enzymes participating in endoergic reactions of patients systemic lupus erythematosus and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    LA Zborovskaya

    2004-01-01

    Full Text Available Objective. To improve quality of diagnosis of systemic lupus erythematosus (SLE and systemic sclerosis (SS. Material and methods. 30 pts with SLE and 30 with SS were included. Besides complex clinical, instrumental and laboratory examination activity and isoenzymes of succinate dehydrogenase (SDG, fumarate hydrase (FH, malate dehydrogenase (MDG, cytochrome oxidase (CO were evaluated trice (at admission, after two weeks and at discharge with original methods. 30 healthy persons were included in the control group. Results. SLE and SS pts had significant changes of energy metabolism enzymes depended on clinical features of the disease. Enzyme indices at minimal activity of SLE and SS were more informative than most of traditional laboratory tests. Comparative analysis of enzyme indices in SLE and SS pts revealed some features with along with clinical, instrumental and traditional laboratory data should be consider in diagnosis of these diseases. Enzyme indices correlated with changes of pts clinical state what allow to use them as criteria of treatment efficacy.

  5. The role of nailfold capillaroscopy in the assessment of internal organ involvement in systemic sclerosis: A critical review.

    Science.gov (United States)

    Soulaidopoulos, Stergios; Triantafyllidou, Eva; Garyfallos, Alexandros; Kitas, George D; Dimitroulas, Theodoros

    2017-08-01

    Endothelial dysfunction and microvascular damage constitute the hallmarks of systemic sclerosis (SSc), explaining much of the pathophysiology and clinical manifestations of the disease. Nailfold videocapillaroscopy (NVC) is an established method for the assessment of the microvasculature, aiding in distinguishing different types of structural vascular abnormalities. Until recently, NVC was used in the diagnosis of SSc as well as in the assessment and follow-up of peripheral digital vasculopathy. On the top of digital ulcers, internal organ involvement such as myocardial dysfunction, pulmonary vascular and/or parenchymal lung disease characterizes severe SSc imparting a high risk of mortality. There is growing evidence suggesting that the extent of peripheral microvascular changes reflects the severity of the disease, especially in terms of life-threatening cardiopulmonary complications. The possible use of nailfold videocapillaroscopy as a useful, non-invasive modality to improve the ability to identify patients at higher risk for these devastating complications of the disease remains to be established. The aim of this review is to critically summarize and discuss current literature regarding the relationship between morphological alterations of nailfold dermal papillary vessels and several manifestations of SSc, focusing on visceral organ involvement, as well as their association with surrogate markers of macrovascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Progressive systemic sclerosis: high-resolution computed tomography findings; Esclerose sistemica progressiva: aspectos na tomografia computadorizada de alta resolucao

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    Gasparetto, Emerson L.; Pimenta, Rodrigo; Ono, Sergio E.; Escuissato, Dante L. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Radiologia Medica]. E-mail: dante.luiz@onda.com.br; Inoue, Cesar [Parana Univ., Curitiba, PR (Brazil). Faculdade de Medicina

    2005-09-15

    Objective: To describe the high-resolution computed tomography findings in the lung of patients with systemic sclerosis, independently of the respiratory symptoms. Materials and methods: Seventy-three high-resolution computed tomography scans of 44 patients with clinical diagnosis of systemic sclerosis were reviewed and defined by the consensus of two radiologists. Results: Abnormalities were seen in 91.8% (n = 67) of the scans. The most frequent findings were reticular pattern (90.4%), ground-glass opacities (63%), traction bronchiectasis and bronchiolectasis (56.2%), esophageal dilatation (46.6%), honeycombing pattern (28.8%) and signs of pulmonary hypertension (15.6%). In most cases the lesions were bilateral (89%) and symmetrical (58.5%). The lesions were predominantly located in the basal (91.2%) and peripheral (92.2%) regions. Conclusion: In the majority of the patients, progressive systemic sclerosis can cause pulmonary fibrosis mainly characterized by reticular pattern with basal and peripheral distribution on high-resolution computed tomography. (author)

  7. Relationship Between Disease Characteristics and Oral Radiologic Findings in Systemic Sclerosis: Results From a Canadian Oral Health Study.

    Science.gov (United States)

    Baron, Murray; Hudson, Marie; Dagenais, Marie; Macdonald, David; Gyger, Geneviève; El Sayegh, Tarek; Pope, Janet; Fontaine, Audrey; Masetto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira-Filho, Getulio; Robinson, David; Fritzler, Marvin; Wang, Mianbo; Gornitsky, Mervyn

    2016-05-01

    Systemic sclerosis (SSc; scleroderma) is associated with a wide periodontal ligament (PDL) and mandibular erosions. We investigated the clinical correlates of SSc with these radiologic abnormalities. Subjects from the Canadian Scleroderma Research Group cohort underwent detailed radiologic examinations. Associations between radiologic abnormalities and clinical manifestations of SSc were examined with univariate and multivariate analyses. The study included 159 subjects; 90.6% were women, the mean ± SD age was 56 ± 10 years, diffuse disease was present in 28.3%, and mean ± SD disease duration was 13.7 ± 8.4 years. Widening of the PDL involving at least 1 tooth was present in 38% of subjects, and 14.5% had at least 1 site in the mandible with an erosion. In analyses adjusting for age, disease duration, sex, smoking, and education, we found significant associations between the number of teeth with widening of the PDL and disease severity assessed by the physician global assessment (PGA) (relative risk [RR] 1.19, 95% confidence interval [95% CI] 1.02-1.39, P = 0.028). Analyses replacing the PGA with the skin score, disease subset, or anti-topoisomerase I antibodies confirmed the relationship with indices of disease severity. There was no relationship between either the number of teeth with periodontal disease or the number of missing teeth, and the number of teeth with wide PDL. A smaller interdental distance (RR 0.89, 95% CI 0.82-0.97, P = 0.006), but not disease severity, facial skin score, or ischemia was associated with a larger number of erosions. In SSc, a wide PDL may reflect generalized overproduction of collagen, and mandibular erosions are related to local factors in the oral cavity. © 2016, American College of Rheumatology.

  8. The essential role of t cells in multiple sclerosis: A reappraisal

    Directory of Open Access Journals (Sweden)

    Cris S Constantinescu

    2014-04-01

    Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

  9. Specific oxidative stress parameters differently correlate with nailfold capillaroscopy changes and organ involvement in systemic sclerosis.

    Science.gov (United States)

    Riccieri, Valeria; Spadaro, Antonio; Fuksa, Leos; Firuzi, Omidreza; Saso, Luciano; Valesini, Guido

    2008-02-01

    Oxidative stress is suggested to be involved in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to clarify such a hypothesis by determination of four different plasmatic parameters of oxidative stress, and to define its role in the microvascular damage, assessed by nailfold capillaroscopy (NC). Plasma samples of 18 patients with SSc were analyzed. The biomarkers measured were: total antioxidant capacity, hydroperoxides (ROOHs), and sulfhydryl (SH) and carbonyl (CO) groups. Each patient had a detailed clinical assessment and underwent an NC. The results showed significantly increased ROOHs in SSc patients compared to control group (5.02 +/- 0.24 vs 3.28 +/- 0.19 micromol/l; p capillaroscopy semiquantitative rating scale score (p < 0.05) and with the rating system for avascular areas (p < 0.03). The levels of CO groups inversely correlated with modified Rodnan's skin score (p < 0.039) and were lower in patients with pulmonary fibrosis (p < 0.045), while the levels of SH groups were lower in those presenting gastrointestinal involvement (p < 0.029). The obtained data indicate augmented free radical-mediated injury in SSc and also show correlations among oxidative abnormalities, some clinical findings, and signs of a more severe microvascular involvement. These results give more evidence to the connection between oxidative impairment and SSc.

  10. Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center.

    Science.gov (United States)

    Vilela, Verônica Silva; Maretti, Giselle Baptista; Gama, Lívia Marques da Silva; Costa, Claudia Henrique da; Rufino, Rogério Lopes; Levy, Roger A

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B-cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open-label studies. This study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center. We retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected. Ten patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease. Similar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long-term illness may benefit from the treatment. Copyright © 2016. Published by Elsevier Editora Ltda.

  11. Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Katja Lakota

    Full Text Available Inflammation in systemic sclerosis (SSc is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA, a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

  12. Does dysfunction of the mirror neuron system contribute to symptoms in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Eisen, Andrew; Lemon, Roger; Kiernan, Matthew C; Hornberger, Michael; Turner, Martin R

    2015-07-01

    There is growing evidence that mirror neurons, initially discovered over two decades ago in the monkey, are present in the human brain. In the monkey, mirror neurons characteristically fire not only when it is performing an action, such as grasping an object, but also when observing a similar action performed by another agent (human or monkey). In this review we discuss the origin, cortical distribution and possible functions of mirror neurons as a background to exploring their potential relevance in amyotrophic lateral sclerosis (ALS). We have recently proposed that ALS (and the related condition of frontotemporal dementia) may be viewed as a failure of interlinked functional complexes having their origins in key evolutionary adaptations. This can include loss of the direct projections from the corticospinal tract, and this is at least part of the explanation for impaired motor control in ALS. Since, in the monkey, corticospinal neurons also show mirror properties, ALS in humans might also affect the mirror neuron system. We speculate that a defective mirror neuron system might contribute to other ALS deficits affecting motor imagery, gesture, language and empathy. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Prospective evaluation of frequency of signs of systemic sclerosis in 76 patients with morphea.

    Science.gov (United States)

    Lipsker, Dan; Bessis, Didier; Cosnes, Anne; Kluger, Nicolas; Lutz, Virginie; Sauleau, Erik; Francès, Camille

    2015-01-01

    Some authors consider that morphoea and systemic sclerosis (SSc) could be part of the same disease spectrum. The aim of this study was to analyse the prevalence of signs indicative of SSc in a cohort of patients with morphoea. This is a prospective multi-centre study performed in four French academic dermatology departments: 76 patients with morphoea and 101 age- and sex-matched controls, who underwent complete clinical examination, were enrolled. A systemic search for signs indicative of SSc (e.g. Raynaud's phenomenon, reflux) was performed with the help of a standardised questionnaire. There were 58 women and 18 men (ration=3/1) with a median age of 59 years. Mean age at diagnosis was 54 years (extremes, 13-87). 49 subjects had plaque morphoea, 9 had generalised morphoea and 18 had linear morphoea. Mean duration of morphoea was 7.9 years. Signs possibly indicative of SSc were noted in four patients of the control group and in 8 patients with morphoea. This difference was not statistically significant (p=0.129). Further investigations ruled out SSc in all patients. Signs indicative of SSc are statistically not more frequently present in patients with morphoea than in controls and this study does not support the view that those 2 entities are part of a common disease spectrum.

  14. Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

    Directory of Open Access Journals (Sweden)

    Marcelo Chaves

    Full Text Available ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS. Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3 and 13 healthy controls (four females, average age 66.9 + - 2 were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001. Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

  15. HLA-DRB*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis.

    Science.gov (United States)

    Yaldizli, Özgür; Sethi, Varun; Pardini, Matteo; Tur, Carmen; Mok, Kin Y; Muhlert, Nils; Liu, Zheng; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Yousry, Tarek A; Houlden, Henry; Hardy, John; Miller, David H; Chard, Declan T

    2016-05-01

    The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology. To assess HLA-DRB(*)1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology. Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB(*)1501 haplotype was determined by genotyping (rs3135388). No significant differences were observed in MRI measures between the HLA-DRB(*)1501 subgroups. The HLA-DRB(*)1501 haplotype is not strongly associated with MRI-visible grey matter pathology. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Owens, G.R.; Steen, V.D.; Rodnan, G.P.

    1984-01-01

    Myocardial function and perf