Rheumatoid Arthritis: Sánchez-Tapias JM

Ramos-Casals M, Pares A, Jara LJ, Solans R, Viñas O, Vázquez P, Sánchez-Tapias JM, Rodés J, Font J, Anonymous00017. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain. · J Viral Hepat. · Pubmed #16255767 No free full text.

Abstract: To describe the clinical and immunologic patterns of disease expression of patients with chronic hepatitis C virus (HCV) infection and positive antimitochondrial antibodies (AMA). We investigated the presence of AMA in 237 consecutive HCV patients with extrahepatic manifestations from an International Registry. AMA were detected by indirect immunofluorescence in triple rat tissue (liver, stomach and kidney), aceton-fixed criosections and FITC-conjugated rabbit anti-human immunoglobulins. We found positive AMA in 18 (8%) out of 237 HCV patients. All patients were female with a mean age at protocol inclusion of 65.8 years (ranging from 37 to 87 years). Twelve (67%) patients fulfilled classification criteria for systemic autoimmune diseases (SAD), including Sjögren's syndrome (n = 7), systemic sclerosis (n = 3) and systemic lupus erythematosus (n = 2). Fourteen (78%) of the HCV-AMA patients presented at least one of the highly suggestive characteristics of primary biliary cirrhosis (PBC): 9 (50%) had a specific M2 pattern, 6 (33%) had more than twice normal levels of alkaline phosphatase, 5 (28%) had raised IgM levels and 4 (22%) a histological pattern compatible with PBC. Five (28%) patients developed neoplasia after detection of AMA. Seven (39%) patients died, due to neoplasia (n = 4), cirrhotic complications (n = 2) and hepatopulmonary syndrome (n = 1). We describe a subset of HCV patients with positive AMA who presented a broad spectrum of clinical features, including liver, autoimmune and neoplasic manifestations. Two-thirds of these patients presented an associated SAD, mainly Sjögren's syndrome or systemic sclerosis, together with a high frequency of multiple autoantibodies and an increased prevalence of cirrhosis and neoplasia.

Ramos-Casals M, García-Carrasco M, Cervera R, Rosas J, Trejo O, de la Red G, Sánchez-Tapias JM, Font J, Ingelmo M. · Systemic Autoimmune Diseases Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #11204499 No free full text.

Abstract: Hepatitis C virus (HCV) infection is emerging as an extremely common and insidiously progressive liver disease that is often associated with several extrahepatic manifestations. In 1992, a possible relationship between Sjögren syndrome (SS) and patients with HCV infection was first postulated. Subsequently, several studies demonstrated that a "true" SS, with similar clinical and histologic features to those observed in primary SS, may occur in some patients with chronic HCV infection. We report the clinical and immunologic characteristics of 35 patients with chronic HCV infection and a well-documented diagnosis of SS. Compared with 60 patients with primary SS who tested negative for HCV antibodies, SS-HCV patients showed a higher mean age (65.9 yr versus 61.5 yr, p = 0.04), a lower prevalence of parotidomegaly (17% versus 47%, p = 0.004), and a higher prevalence of liver involvement (94% versus 3%, p < 0.001). Moreover, those patients with HCV-related SS showed a higher prevalence of anti-parietal cell gastric antibodies (31% versus 13%, p = 0.03), antimitochondrial antibodies (14% versus 2%, p = 0.02), cryoglobulinemia (60% versus 10%, p < 0.001), hypocomplementemia (60% versus 8%, p < 0.001), and a lower prevalence of anti-Ro/SS-A (17% versus 38%, p = 0.03). The "true" SS observed in some patients with HCV may be considered 1 of the extrahepatic manifestations of HCV, and we suggest that HCV infection can be considered as an exclusion criterion for the diagnosis of primary SS.

Ramos-Casals M, Muñoz S, Medina F, Jara LJ, Rosas J, Calvo-Alen J, Brito-Zerón P, Forns X, Sánchez-Tapias JM, Anonymous00071. · Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, 08036-Barcelona, Spain. · J Rheumatol. · Pubmed #19369460 No free full text.

Abstract: OBJECTIVE: To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection. METHODS: The HISPAMEC Registry is a multicenter international study group dedicated to collecting data on patients diagnosed with SAD with serological evidence of chronic HCV infection. The information sources are cases reported by physicians of the HISPAMEC Study Group and periodic surveillance of reported cases by a Medline search updated up to December 31, 2007. RESULTS: One thousand twenty HCV patients with SAD were included in the registry. Patients were reported from Southern Europe (60%), North America (15%), Asia (14%), Northern Europe (9%), South America (1%), and Australia (1%). Countries reporting the most cases were Spain (236 cases), France (222 cases), Italy (144 cases), USA (120 cases), and Japan (95 cases). The most frequently reported SAD were Sjögren's syndrome (SS; 483 cases), rheumatoid arthritis (RA; 150 cases), systemic lupus erythematosus (SLE; 129 cases), polyarteritis nodosa (78 cases), antiphospholipid syndrome (59 cases), inflammatory myopathies (39 cases), and sarcoidosis (28 cases). Twenty patients had 2 or more SAD. Epidemiological data were available in 677 cases. Four hundred eighty-seven (72%) patients were female and 186 (28%) male, with a mean age of 49.5 +/- 1.0 years at SAD diagnosis and 50.5 +/- 1.1 years at diagnosis of HCV infection. The main immunologic features were antinuclear antibody (ANA) in 61% of patients, rheumatoid factor (RF) in 57%, hypocomplementemia in 52%, and cryoglobulins in 52%. The main differential aspect between primary and HCV-related SAD was the predominance of cryoglobulinemic-related markers (cryoglobulins, RF, hypocomplementemia) over specific SAD-related markers (anti-ENA antibodies, anti-dsDNA, anti-cyclic citrullinated peptide) in patients with HCV. CONCLUSION: In the selected cohort, the SAD most commonly reported in association with chronic HCV infection were SS (nearly half the cases), RA and SLE. Nearly two thirds of SAD-HCV cases were reported from the Mediterranean area. In these patients, ANA, RF and cryoglobulins are the predominant immunological features.

Ramos-Casals M, Sánchez-Tapias JM, Parés A, Forns X, Brito-Zerón P, Nardi N, Vazquez P, Vélez D, Arias I, Bové A, Plaza J, Rodés J, Font J. · Department of Autoimmune Diseases and Hepatology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, IDIBAPS, School of Medicine, University of Barcelona, Barcelona, Spain. · J Rheumatol. · Pubmed #16881116 No free full text.

Abstract: OBJECTIVE: To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease. METHODS: We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS. RESULTS: Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001). CONCLUSION: Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.

Ramos-Casals M, García-Carrasco M, Cervera R, Filella X, Trejo O, de la Red G, Gil V, Sánchez-Tapias JM, Font J, Ingelmo M. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain. · Semin Arthritis Rheum. · Pubmed #12219321 No free full text.

Abstract: OBJECTIVE: To investigate if the serum immunologic profile, as delineated by serum circulating levels of Th1/Th2 cytokines and autoantibodies, is different in patients with Sjögren syndrome (SS) with and without hepatitis C virus (HCV) infection. METHODS: This study included 20 patients with HCV-related SS and 47 consecutive patients with primary SS. All fulfilled 4 or more of the modified 1996 European criteria for SS. Serum levels of interleukin (IL)-2 (pg/mL), srIL-2 (pM), tumor necrosis factor (TNF)-alpha (pg/mL), IL-6 (pg/mL), and IL-10 (pg/mL) were determined using enzyme immunoassay. We also analyzed the following immunologic tests: anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-parietal cell antibodies (PCA), anti-smooth muscle antibodies (SMA), anti-liver-kidney microsome antibodies type-1 (LKM-1), anti-Ro/SS-A, anti-La/SS-B, rheumatoid factor (RF), complement factors (C3 and C4), and cryoglobulins. RESULTS: Of the 20 patients with HCV-related SS, 18 were women and 2 men (mean age, 66 years). Patients with HCV-related SS had a different cytokine profile compared with patients with primary SS, with higher circulating levels of IL-6 (73.6 v 33.0 pg/mL, P =.045), IL-10 (6.7 v 3.1 pg/mL, P =.01), srIL-2 (124.6 v 72.7 pM, P =.001), and TNF-alpha (59.8 v 31.7 pg/mL, P =.003). The main immunologic features were ANA, detected in 75% of patients, RF in 63%, cryoglobulinemia in 50%, hypocomplementemia in 40%, SMA in 30%, PCA in 25%, anti-Ro/SS-A in 25%, AMA in 20% and anti-La/SS-B in 16%. When compared with primary SS patients, those with HCV-related SS had a higher prevalence of AMA (20% v 2%, P =.025), hypocomplementemia (40% v 11%, P =.015), and cryoglobulinemia (50% v 12%, P =.003). CONCLUSION: Although chronic HCV infection may mimic the main clinical, histologic and immunologic features of primary SS, patients with HCV-related SS showed some differentiated characteristics, including a predominant Th2 pattern and a higher frequency of cryoglobulinemia and hypocomplementemia (features closely related to HCV). This suggests that the SS observed in some HCV patients should be interpreted as one of the extrahepatic manifestations of chronic HCV infection.