Rheumatoid Arthritis: Medina F

Macías I, García-Pérez S, Ruiz-Tudela M, Medina F, Chozas N, Girón-González JA. · Rheumatology Service, Hospital Universitario Puerta del Mar, Cádiz, Spain. · J Rheumatol. · Pubmed #16265686 No free full text.

Abstract: OBJECTIVE: Analysis of serum concentrations and modifications of tumor necrosis factor-a (TNF-a), its soluble receptors (TNFR), interleukin 10 (IL-10), and vascular related molecules [soluble vascular cell adhesion molecule 1 (sVCAM-1), vascular endothelial growth factor (VEGF)] after therapy with methotrexate (MTX) and anti-TNF (infliximab) in patients with rheumatoid arthritis (RA). METHODS: Thirty-six patients with RA and 20 healthy controls were included. Patients had been orally taking a stable dose of MTX of at least 12.5 mg/week for a minimum of 6 months before inclusion in the study. Twenty-five patients had shown a clinical response to MTX (MTX Group). The other 11 had shown an unsatisfactory response and presented with active RA; they were selected for additional treatment with infliximab (MTX + IFM Group). Disease activity score (DAS28), hemoglobin concentration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum levels of TNF-a, soluble TNFR, IL-10, sVCAM-1 and VEGF were determined at baseline and prior to every infusion of infliximab (3 mg/kg) at 2, 6, 14, 22, and 30 weeks. RESULTS: Although serum levels of TNF-a were similar in patients and controls, patients showed significantly higher concentrations of both soluble TNFR (sTNFR55 and sTNFR75), IL-10, sVCAM-1, and VEGF than healthy individuals. Significantly higher levels of sVCAM-1 and VEGF, but not of the other tested molecules, were detected in those with active disease. After infliximab treatment (MTX + IFM Group) there was a significant decrease in DAS28 and modified Health Assessment Questionnaire scores and ESR and CRP levels. Serum concentration of VEGF showed a significant decrease after infliximab, with levels comparable to those of patients with inactive RA, although VEGF continued to present higher values than in healthy controls. CONCLUSION: Increased levels of vascular related molecules sVCAM-1 and VEGF are serum markers of active RA. The absence of normalization of levels of these molecules in patients with inactive RA could be one of the reasons response to therapy is only temporary.

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, la Civita L, de Vita S, Solans R, Luppi M, Medina F, Caramaschi P, Fadda P, de Marchi G, Lopez-Guillermo A, Font J, Anonymous00869. · Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, School of Medicine, University of Barcelona, Barcelona, Spain. · Arthritis Rheum. · Pubmed #17266090 links to  free full text

Abstract: OBJECTIVE: To characterize the clinical and immunologic patterns of expression, response to therapy, and outcome of patients with Sjögren's syndrome (SS) and associated hepatitis C virus (HCV) infection who developed B cell lymphoma. METHODS: Various international reference centers constituted a multicenter study group with the purpose of creating a registry of patients with SS-HCV who developed B cell lymphoma. A protocol form was used to record the main characteristics of SS, chronic HCV infection, and B cell lymphoma. RESULTS: Twenty-five patients with SS-HCV with B cell lymphoma were included in the registry. There were 22 (88%) women and 3 (12%) men (mean age 55, 58, and 61 years at SS, HCV infection, and lymphoma diagnosis, respectively). The main extraglandular SS manifestations were cutaneous vasculitis in 15 (60%) patients and peripheral neuropathy in 12 (48%); the main immunologic features were positive rheumatoid factor (RF) in 24 (96%) and type II cryoglobulins in 20 (80%). The main histologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 11 (44%) patients, diffuse large B cell lymphoma in 6 (24%), and follicular center cell lymphoma in 6 (24%). Fifteen (60%) patients had an extranodal primary location, most frequently in the parotid gland (5 patients), liver (4 patients), and stomach (4 patients). Twelve (52%) of 23 patients died after a median followup from the time of lymphoma diagnosis of 4 years, with lymphoma progression being the most frequent cause of death. Survival differed significantly between the main types of B cell lymphoma. CONCLUSION: Patients with SS-HCV and B cell lymphoma are clinically characterized by a high frequency of parotid enlargement and vasculitis, an immunologic pattern overwhelmingly dominated by the presence of RF and mixed type II cryoglobulins, a predominance of MALT lymphomas, and an elevated frequency of primary extranodal involvement in organs in which HCV replicates (exocrine glands, liver, and stomach).

Ramos-Casals M, Jara LJ, Medina F, Rosas J, Calvo-Alen J, Mañá J, Anaya JM, Font J, Anonymous00031. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, School of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain. · J Intern Med. · Pubmed #15910559 No free full text.

Abstract: OBJECTIVES: 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: We analysed 180 patients diagnosed with SAD and chronic HCV infection seen consecutively at our centres during the last 10 years. The clinical and immunological patterns of disease expression were compared with 180 SAD-matched patients without chronic HCV infection. RESULTS: A total of 180 HCV patients fulfilled the classification criteria for the following SAD: Sjogren's syndrome (n = 77), systemic lupus erythematosus (n = 43), rheumatoid arthritis (n = 14), antiphospholipid syndrome (n = 14), polyarteritis nodosa (n = 8) and other SAD (n = 24). One hundred and thirty (72%) patients were female and 50 (28%) male, with a mean age at SAD diagnosis of 50 years. The main immunologic features were antinuclear antibodies in 69% of patients, cryoglobulinaemia in 62%, hypocomplementaemia in 56% and rheumatoid factor (RF) in 56%. Compared with the SAD-matched HCV-negative group, SAD-HCV patients presented a lower prevalence of females (P = 0.016), an older age at SAD diagnosis (P = 0.039) and a higher prevalence of vasculitis (P < 0.001) and neoplasia (P < 0.001). Immunologically, SAD-HCV patients presented a lower prevalence of antinuclear (P = 0.036), anti-extractable nuclear antigen (P = 0.038) and anti-DNA (P = 0.005) antibodies, and a higher frequency of RF (P = 0.003), hypocomplementaemia (P < 0.001) and cryoglobulins (P < 0.001). CONCLUSIONS: In comparison with an SAD-matched HCV-negative population, SAD-HCV patients were older and more likely to be male, with a higher frequency of vasculitis, cryoglobulinaemia and neoplasia. This complex pattern of disease expression is generated by a chronic viral infection that induces both liver and autoimmune disease.

Ramos-Casals M, Loustaud-Ratti V, De Vita S, Zeher M, Bosch JA, Toussirot E, Medina F, Rosas J, Anaya JM, Font J, Anonymous00012. · Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #15758837 No free full text.

Abstract: To define the clinical and immunologic pattern of expression of Sjögren syndrome (SS) associated with chronic hepatitis C virus (HCV) infection, we conducted a multicenter study aiming to collect a large number of patients with SS and HCV infection. Inclusion criteria were the fulfillment of at least 4 of the classification criteria for SS proposed by the European Community Study Group and repeated positive HCV serology, confirmed by recombinant immunoblot assay and/or detection of serum HCV-RNA by polymerase chain reaction. One hundred thirty-seven patients were included (104 female and 33 male; mean age, 65 yr). Seventy-nine (58%) patients presented a systemic process with diverse extraglandular manifestations, with articular involvement (44%), vasculitis (20%), and neuropathy (16%) being the most frequent features observed. The main immunologic features were antinuclear antibodies (65%), hypocomplementemia (51%), and cryoglobulinemia (50%). Cryoglobulins were associated with a higher frequency of cutaneous vasculitis, rheumatoid factor, and hypocomplementemia. Thirty-two (23%) patients had positive anti-Ro/SS-A and/or anti-La/SS-B antibodies; these patients were predominantly women and had a higher prevalence of some extraglandular features and a lower frequency of liver involvement. Nineteen (14%) patients developed neoplasia, with hematologic neoplasia (8 cases) and hepatocellular carcinoma (6 cases) being the most frequent types. Eighty-five percent of SS-HCV patients also fulfilled the recently proposed 2002 classification criteria for SS.In conclusion, HCV-associated SS is indistinguishable in most cases from the primary form using the most recent set of classification criteria. Chronic HCV 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. We propose the term "SS secondary to HCV" when these patients fulfill the 2002 classification criteria for SS.

Aceves-Avila FJ, Medina F, Fraga A. · Servicio de Reumatología, Hospital General Regional No. 46, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, DF México. · J Rheumatol. · Pubmed #11327245 No free full text.

Abstract: OBJECTIVE: To demonstrate the existence of rheumatoid arthritis (RA) before the 19th century. METHODS: Survey of primary and secondary references on the history of rheumatic diseases. RESULTS: Paleopathological evidence suggests the existence of RA in America since 8000 BC and in Europe since the 7th century. Descriptions and representations of a symmetric chronic polyarthritis producing characteristic deformities can be found in Rome since 100 BC and India since 500 BC. The first clinical distinction between RA and gout was published in Mexico in 1578. Different historical conditions contributed to lack of recognition of RA by official medicine before 1800. The recognition of RA as a distinct entity in the 19th century was influenced by socioeconomic circumstances. CONCLUSION: RA is not a recent disease. Historical investigation can provide useful clues on its pathogeny.