Rheumatoid Arthritis: Muñoz S

Ramos-Casals M, Muñoz S, Zerón PB. · Laboratory of Autoimmune Diseases "Josep Font," IDIBAPS, Department of Autoimmune Diseases, C/Villaroel 170, Hospital Clinic, Barcelona 08036, Spain. · Rheum Dis Clin North Am. · Pubmed #18984409 No free full text.

Abstract: Patients who have chronic hepatitis C virus infection present some extrahepatic manifestations that may mimic the clinical, immunologic, and histologic manifestations of primary Sjögren's syndrome (SS). Various demographic, clinical, and immunologic features may aid differentiation between the two processes. Chronic hepatitis C virus infection should be considered an exclusion criterion for the classification of primary SS, not because it mimics primary SS, but because the virus may be implicated in the development of SS in a specific subset of patients.

Riedemann JP, Muñoz S, Kavanaugh A. · Department of Rheumatology and Clinical Epidemiology, Faculty of Medicine, Universidad de la Frontera, Temuco, Chile. · Clin Exp Rheumatol. · Pubmed #16273788 No free full text.

Abstract: OBJECTIVE: To evaluate the diagnostic properties and predictive value of the second generation of anti-CCP antibodies (anti-CCP2) in rheumatoid arthritis (RA) patients. METHODS: A systematic review of the published literature between January 2002 and June 2005 was performed. Data were extracted regarding the sensitivity and specificity of anti-CCP2 antibodies in making an accurate diagnosis of RA, predicting future development of RA, and predicting future radiological damage in RA patients. In addition, the prevalence of CCP2 antibodies in patients with other rheumatic diseases was examined. RESULTS: Among 38 studies initially identified, 27 provided information on the use of anti-CCP2 testing. Diagnostic properties were assessed in 13 studies; reported sensitivities ranged from 14.4% to 96%, and specificities from 88.9% to 100%. Odds ratios (OR) for the future development of RA varied from 15.9 among previously healthy individuals to 37.8 among a group of patients with undifferentiated arthritis. Several studies suggested that the presence of anti-CCP2 antibodies is highly predictive of current radiographic damage and further damage progression. CONCLUSIONS: Anti-CCP2 has a low sensitivity to be used as a screening test. However, a positive test is highly specific for RA. In addition, anti-CCP2 appears to be highly predictive of the future development of RA in both normal individuals and patients with undifferentiated arthritis. Finally, the presence of anti-CCP2 antibodies appears to predict radiographic damage and progression among patients with RA.

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, 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, Brito-Zerón P, Muñoz S, Soria N, Galiana D, Bertolaccini L, Cuadrado MJ, Khamashta MA. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Hospital Clínic, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #17632266 No free full text.

Abstract: Tumor necrosis factor (TNF)-targeted therapies are increasingly used for a rapidly expanding number of rheumatic and autoimmune diseases. With this use and longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. We have analyzed the clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy found through a MEDLINE search of articles published between January 1990 and December 2006. We identified 233 cases of autoimmune diseases (vasculitis in 113, lupus in 92, interstitial lung diseases in 24, and other diseases in 4) secondary to TNF-targeted therapies in 226 patients. The anti-TNF agents were administered for rheumatoid arthritis (RA) in 187 (83%) patients, Crohn disease in 17, ankylosing spondylitis in 7, psoriatic arthritis in 6, juvenile RA in 5, and other diseases in 3. The anti-TNF agents administered were infliximab in 105 patients, etanercept in 96, adalimumab in 21, and other anti-TNF agents in 3. We found 92 reported cases of lupus following anti-TNF therapy (infliximab in 40 cases, etanercept in 37, and adalimumab in 15). Nearly half the cases fulfilled 4 or more classification criteria for systemic lupus erythematosus (SLE), which fell to one-third after discarding preexisting lupus-like features. One hundred thirteen patients developed vasculitis after receiving anti-TNF agents (etanercept in 59 cases, infliximab in 47, adalimumab in 5, and other agents in 2). Leukocytoclastic vasculitis was the most frequent type of vasculitis, and purpura was the most frequent cutaneous lesion. A significant finding was that one-quarter of patients with vasculitis related to anti-TNF agents had extracutaneous involvement. Twenty-four cases of interstitial lung disease associated with the use of anti-TNF agents were reported. In these patients, 2 specific characteristics should be highlighted: the poor prognosis in spite of cessation of anti-TNF therapy, and the possible adjuvant role of concomitant methotrexate. In conclusion, the use of anti-TNF agents has been associated with an increasing number of cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, SLE, and interstitial lung disease.

Cuchacovich M, Gatica H, Muñoz S, González P. · Departamento de Medicina Interna, Hospital Clínico Dr. José Joaquín Aguirre, Santiago de Chile. · Rev Med Chil. · Pubmed #10962872 No free full text.

Abstract: BACKGROUND: No reliable variables to predict clinical or laboratory response to treatment in patients with rheumatoid arthritis were available until recently. AIM: To asses the potential predictive value of the Sharp's modified radiographic joint damage index for the assessment of clinical and laboratory response to a methylprednisolone i.v. pulse. PATIENTS AND METHODS: Twenty-two patients suffering from rheumatoid arthritis received a single i.v. pulse of 1 g of methylprednisolone. Hand X-rays were taken at baseline and blindly scored by two trained radiologists. Clinical and laboratory variables were assessed at baseline and at weekly intervals up to 30 days plus a 60 days final evaluation. Improvement was defined as a 50% amelioration in 4 variables. RESULTS: Assessment of radiographic scores had a high correlation between and within observers (intraclass correlation = 0.998). Sharp score did not reach statistical significance as global predictor for the inflammatory variable response to methylprednisolone. However, when the number of swollen joints was taken into account, patients with a low erosive score (Sharp < or = 50) had a more prolonged clinical response, than patients with higher erosive score (Sharp > 50) (Fisher test p = 0.023). It is of clinical importance to point out that among patients with high Sharp score there were also responders who reached a high level of improvement. A statistically significant correlation between the basal PCR serum titers and the radiographic score (p < 0.02) was observed. CONCLUSIONS: The number of swollen joints and other variables that consider joint structural changes should be considered for the assessment of rheumatoid arthritis patients.