Rheumatoid Arthritis: Bové A

Ramos-Casals M, Brito-Zerón P, Soria N, Nardi N, Vargas A, Muñoz S, Bové A, Suárez B, Lozano F. · Department of Autoimmune Diseases, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. · Rheumatology (Oxford). · Pubmed #19056797 No free full text.

Abstract: OBJECTIVE: To investigate the association of mannose-binding lectin (MBL)-low genotypes with the clinical and immunological expression of primary SS. METHODS: Eighty-one patients with primary SS who fulfilled the 2002 classification criteria were included in the study. MBL2 polymorphisms were investigated by sequence-based DNA typing of the promoter and exon 1. Genotypes 0/0, 0/XA or XA/XA were considered as MBL-low and XA/A, A/0 and A/A as MBL-sufficient. Control groups included 46 patients who exclusively fulfilled the 1993 SS criteria, 114 SLE patients and 104 healthy individuals. RESULTS: Twelve (15%) SS patients had MBL-low genotypes, of whom six (7%) had genotype 0/XA, five (6%) had genotype 0/0 and one (1%) had genotype XA/XA. A higher prevalence of the XA/A genotype (32 vs 17%, P = 0.01) was found in primary SS patients in comparison with SLE patients. No patient with primary SS carrying MBL-low genotypes had purpura, glomerulonephritis or neurological involvement (0 vs 29%, P = 0.025). Immunologically, patients carrying MBL-low genotypes had a lower frequency of anti-Ro/SS-A antibodies (17 vs 55%, P = 0.014), anti-La/SS-B antibodies (8 vs 48%, P = 0.009) and low C4/C3 levels (0 vs 32%, P = 0.016). No patient with primary SS carrying the homozygous MBL-deficient genotype 0/0 had anti-Ro/SS-A or anti-La/SS-B antibodies, low C3/C4 levels or circulating cryoglobulins. CONCLUSION: SS patients with MBL-low genotypes have a less pronounced systemic and immunological disease expression in comparison with those carrying MBL-sufficient genotypes. In primary SS, MBL deficiency may represent a protective factor against the development of more aggressive autoimmune damage.

Brito-Zerón P, Soria N, Muñoz S, Bové A, Akasbi M, Belenguer R, Sisó A, Ramos-Casals M. · Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain. · Semin Arthritis Rheum. · Pubmed #18378278 No free full text.

Abstract: OBJECTIVE: To analyze the prevalence of neutropenia in a large cohort of patients with primary Sjögren's syndrome (SS) and its association with clinical and immunological disease expression and adverse outcomes. METHODS: The study cohort included 300 patients diagnosed with primary SS in our department between 1984 and 2002. The outcomes measured after the first laboratory evidence of neutropenia (<2.5 x 10(9)/L) were first hospital admission caused by infection, development of systemic manifestations, neoplasia, and death. RESULTS: Ninety-nine (33%) patients had neutropenia during the follow-up, which was related to neoplasia or drugs in 9 (3%) patients and was considered idiopathic in the remaining 90 (30%). Patients with neutropenia had a lower mean age at diagnosis of SS (51.9 versus 59.4 years, P < 0.001) and a higher prevalence of anti-Ro/La antibodies (53% versus 22%, P < 0.001), rheumatoid factor (49% versus 32%, P = 0.009), and low C4 levels (17% versus 8%, P = 0.044) than those without neutropenia. Patients with neutropenia had a higher incidence of hospital admission caused by infection (24% versus 9%, P = 0.002), especially those with neutropenia <1 x 10(9)/L (50% versus 9%, P = 0.002), and a higher rate of admission (log rank = 0.0023) in comparison with those without neutropenia. Agranulocytosis was found in 7 (2%) patients, predominantly related to neoplasia (5 cases). One (1%) of the 90 patients with SS-related neutropenia developed large granular lymphocyte T-cell leukemia. CONCLUSION: Neutropenia should be considered a relevant hematologic finding of primary SS, due both to its elevated prevalence and to its clinical significance (close association with anti-Ro/La antibodies, coexistence with other cytopenias, and development of severe infections).

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, Nardi N, Brito-Zerón P, Aguiló S, Gil V, Delgado G, Bové A, Font J. · Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain. · Semin Arthritis Rheum. · Pubmed #16616154 No free full text.

Abstract: OBJECTIVES: To analyze the clinical characteristics, follow-up, and fulfillment of classification criteria for other systemic autoimmune diseases (SAD) in patients with primary Sjögren syndrome (SS) and atypical autoantibodies. METHODS: We studied 402 patients diagnosed with primary SS seen consecutively in our Department since 1994. We considered anti-DNA, anti-Sm, anti-RNP, anti-topoisomerase1/Scl70, anticentromere (ACA), anti-Jo1, anti-neutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aPL), and lupus anticoagulant as atypical autoantibodies. The patients were prospectively followed after inclusion into the protocol, focusing on the development of features that might lead to the fulfillment of classification criteria for additional SAD. As a control group, we selected an age-sex-matched subset of patients with primary SS without atypical autoantibodies. RESULTS: Eighty-two (20%) patients showed atypical autoantibodies (36 had aPL, 21 anti-DNA, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70, and 1 anti-Jo-1 antibodies). There were 77 (94%) women and 5 (6%) men, with a mean age of 57 years. Patients with atypical autoantibodies had no statistical differences in the prevalence of the main sicca features, extraglandular manifestations (except for a higher prevalence of Raynaud's phenomenon, 28% versus 7%, P=0.001), immunological markers, and in the fulfillment of the 2002 classification criteria, compared with the control group. After a follow-up of 534 patient-years, 13 (16%) of the 82 patients with atypical autoantibodies developed an additional SAD (systemic lupus erythematosus in 5 cases, antiphospholipid syndrome in 4, limited scleroderma in 3, and microscopic polyangiitis in 1) compared with none in the control group (P<0.001). CONCLUSIONS: This study shows an immunological overlap (defined by the presence of autoantibodies considered typical of other SAD) in 20% of our patients with primary SS. However, the clinical significance of these atypical autoantibodies varies widely depending on the autoantibodies detected, with a broad spectrum of prevalence and clinical patterns of disease expression, and a specific predilection for association with some SAD in preference to others.

Ramos-Casals M, Anaya JM, García-Carrasco M, Rosas J, Bové A, Claver G, Diaz LA, Herrero C, Font J. · Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #15028963 No free full text.

Abstract: To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr).The main cutaneous involvement was cutaneous vasculitis, present in 52 (58%) patients. There were 51 (98%) female patients and 1 (2%) male, with a mean age at diagnosis of cutaneous vasculitis of 51 years (range, 20-80 yr). Fourteen presented with cryoglobulinemic vasculitis, 11 with urticarial vasculitis, and the remaining 26, with cutaneous purpura not associated with cryoglobulins. A skin biopsy specimen was obtained in 38 patients (73%). Involvement of small-sized vessels was observed in 36 (95%) patients (leukocytoclastic vasculitis), while the remaining 2 (5%) presented with medium-sized vessel vasculitis (necrotizing vasculitis). Patients with cutaneous vasculitis had a higher prevalence of articular involvement (50% vs 29%, p = 0.044), peripheral neuropathy (31% vs 4%, p < 0.001), Raynaud phenomenon (40% vs 15%, p = 0.008), renal involvement (10% vs 0%, p = 0.028), antinuclear antibodies (88% vs 60%, p = 0.002), rheumatoid factor (78% vs 48%, p = 0.004), anti-Ro/SS-A antibodies (70% vs 43%, p = 0.011), and hospitalization (25% vs 4%, p = 0.005) compared with SS patients without vasculitis. Six (12%) patients died, all of whom had multisystemic cryoglobulinemia.In conclusion, cutaneous involvement was detected in 16% of patients with primary SS, with cutaneous vasculitis being the most frequent process. The main characteristics of SS-associated cutaneous vasculitis were the overwhelming predominance of small versus medium vessel vasculitis and leukocytoclastic versus mononuclear vasculitis, with a higher prevalence of extraglandular and immunologic SS features. Small vessel vasculitis manifested as palpable purpura, urticarial lesions, or erythematosus maculopapules, with systemic involvement in 44% of patients in association with cryoglobulins in 30%. Life-threatening vasculitis was closely related to cryoglobulinemia.

Font J, Ramos-Casals M, de la Red G, Pou A, Casanova A, García-Carrasco M, Cervera R, Molina JA, Valls J, Bové A, Ingelmo M, Graus F. · Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. · J Rheumatol. · Pubmed #12858457 No free full text.

Abstract: OBJECTIVE: To study the clinical course, response to therapy, and longterm outcome of pure sensory neuropathy (PSN) in a series of patients with primary Sjögren's syndrome (SS) followed prospectively in our referral centers. METHODS: We studied 15 patients (13 women, 2 men) with primary SS and PSN. All patients fulfilled 4 or more of the European diagnostic criteria. RESULTS: At diagnosis of PSN, clinical manifestations included numbness and paresthesias (11 patients), trigeminal neuropathy (6 patients), and Adie's pupil syndrome (4 patients). In 7 patients, PSN was diagnosed prior to SS, in 5 the diagnoses were made simultaneously, and in the remaining 3 patients PSN was diagnosed after the appearance of SS symptomatology. The mean duration of the prospective PSN followup was 10 years (range 1-20). The progression of PSN was acute in 1 patient (producing severe dysfunction in less than 1 month), subacute in 3 patients, and in the remaining 11, the symptoms progressed slowly over the ensuing years to other extremities. Patients were treated with corticosteroids (n = 13), cyclophosphamide (n = 4), and intravenous immunoglobulins (n = 1), and 2 patients received no treatment. In spite of treatment, most patients showed an indolent and insidious longterm PSN course. CONCLUSION: We found 3 differentiated clinical courses of the PSN in patients with primary SS: subacute progression in less than 1 month (7%), late acceleration of PSN 2-4 years after an initial indolent onset (20%), and a very longterm insidious, chronic evolution (73%). Prospective analysis of the longterm course of PSN shows a chronic and insidious evolution in most patients with PSN and SS, with a poor response to treatment, although stabilization of symptomatology for long periods is often observed.