Rheumatoid Arthritis: García-Carrasco M

García-Carrasco M, Escárcega RO. · No affiliation provided · Ann Hepatol. · Pubmed #17060872 No free full text.

This publication has no abstract.

Jara LJ, Navarro C, Brito-Zerón Mdel P, García-Carrasco M, Escárcega RO, Ramos-Casals M. · Direction of Education and Research, Hospital de Especialidades, Centro Médico La Raza, IMSS, Seris y Zaachila s/n C.P., 02990, Mexico City, México. · Clin Rheumatol. · Pubmed #17558463 No free full text.

Abstract: From 1960 to 2007, an important number of patients with primary Sjögren's syndrome (pSS) along with thyroid disease diagnosed by laboratory data and clinical presentation were reported. The most common thyroid disorder found was autoimmune thyroiditis and the most common hormonal pattern was subclinical hypothyroidism. The coexistence of SS and thyroiditis is frequent and suggests a common genetic or environmental factor predisposition with similar pathogenic mechanisms. pSS was ten times more frequent in patients with autoimmune thyroid disease and autoimmune thyroiditis was nine times more frequent in pSS. Therefore, SS should be studied in patients with thyroid disease and vice versa. Antigens are shared by both thyroid and salivary glands, which could be responsible for the association between both diseases. Immunogenetic studies had suggested that both diseases have a common genetic predisposition. pSS and thyroid disease patients were mostly women with positive antithyroglobulin, antiparietal cell and antithyroid peroxidase antibodies. Thyroid dysfunction is frequent in pSS patients and those prone to develop thyroid disorders are identified by thyroid-related autoantibodies or by rheumatoid factor and anti-Ro/SSA activity. Patients with pSS have an increased tendency to develop other autoimmune diseases. Hypothyroidism was the most common autoimmune disease developed in pSS patients during follow-up of 10.5 years. Lymphomas are also associated with SS and thyroiditis and a 67-fold increased risk for thyroid mucosa-associated lymphoid tissue (MALT) lymphoma and a 44-fold increased risk for parotid lymphoma is being attributed to autoimmune thyroiditis and pSS. It is suggested that immune mechanism deficiency is a causal factor for B cell lymphoma in pSS and autoimmune thyroid disease. Other studies are necessary to clarify the shared pathogenesis mechanism in SS and autoimmune thyroid disease and to understand this fascinating autoimmune association.

García-Carrasco M, Fuentes-Alexandro S, Escárcega RO, Salgado G, Riebeling C, Cervera R. · Systemic Autoimmune Disease Research Unit, HGZ #36 CMN Manuel Avila Camacho, IMSS, Puebla, Mexico. · Arch Med Res. · Pubmed #17045106 No free full text.

Abstract: The term Sjögren's syndrome refers to keratoconjunctivitis sicca and xerostomia due to lymphocytic infiltrates of lachrymal and salivary glands. The current used criteria for diagnosis of primary Sjögren's syndrome is the American-European consensus. Primary Sjögren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lachrymal glands and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The infiltrating cells (T- and B-cells, dendritic cells) interfere with glandular function at several points: destruction of glandular elements by cell-mediated mechanisms; secretion of cytokines that activate pathways bearing the signature of type 1 and 2 interferons; production of autoantibodies that interfere with muscarinic receptors; and secretion of metalloproteinases (MMPs) that interfere with the interaction of the glandular cell with its extracellular matrix, which is necessary for efficient glandular function. As the process progresses, the mucosal surfaces become sites of chronic inflammation and the start of a vicious circle. Despite extensive study of the underlying cause of Sjögren's syndrome, the pathogenesis remains obscure. In broad terms, pathogenesis is multifactorial; environmental factors are thought to trigger inflammation in individuals with a genetic predisposition to the disorder.

Cervera R, Asherson RA, Acevedo ML, Gómez-Puerta JA, Espinosa G, De La Red G, Gil V, Ramos-Casals M, García-Carrasco M, Ingelmo M, Font J. · Servei de Malalties Autoimmunes, Hospital Clínic, Villarroel 170, 08036-Barcelona, Catalonia, Spain. · Ann Rheum Dis. · Pubmed #15361392 links to  free full text

Abstract: OBJECTIVE: To describe and analyse the clinical characteristics of 100 patients with antiphospholipid syndrome (APS) associated with infections. METHODS: Patients were identified by a computer assisted search (Medline) of published reports to locate all cases of APS published in English, Spanish, and French from 1983 to 2003. The bilateral Fisher exact test was used for statistics. RESULTS: 59 female and 41 male patients were identified (mean (SD) age, 32 (18) years (range 1 to 78)): 68 had primary APS, 27 had systemic lupus erythematosus, two had "lupus-like" syndrome, two had inflammatory bowel disease, and one had rheumatoid arthritis. APS presented as a catastrophic syndrome in 40% of cases. The main clinical manifestations of APS included: pulmonary involvement (39%), skin involvement (36%), and renal involvement (35%; nine with renal thrombotic microangiopathy, RTMA). The main associated infections and agents included skin infection (18%), HIV (17%), pneumonia (14%), hepatitis C (13%), and urinary tract infection (10%). Anticoagulation was used in 74%, steroids in 53%, intravenous immunoglobulins in 20%, cyclophosphamide in 12%, plasma exchange in 12%, and dialysis in 9.6%. Twenty three patients died following infections and thrombotic episodes (16 with catastrophic APS). Patients given steroids had a better prognosis (p = 0.024). The presence of RTMA and requirement for dialysis carried a worse prognosis (p = 0.001 and p = 0.035, respectively). CONCLUSIONS: Various different infections can be associated with thrombotic events in patients with APS, including the potentially lethal subset termed catastrophic APS. Aggressive treatment with anticoagulation, steroids, and appropriate antibiotic cover is necessary to improve the prognosis.

Ramos-Casals M, Brito-Zerón P, García-Carrasco M, Font J. · Department of Autoimmune Diseases, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Hospital Clínic, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #15028962 No free full text.

Abstract: We present 5 new cases of coexisting sarcoidosis and Sjögren syndrome (SS) and review the literature for additional cases in order to analyze the clinical, immunologic, and histologic characteristics that may help physicians differentiate the mimicry of SS by sarcoidosis from a true coexistence of both autoimmune diseases. We considered the coexistence of sarcoidosis with SS to be when patients presented specific histologic patterns of both diseases, simultaneously or at different times.Fifty-nine patients were included in the analysis (54 identified in the literature search plus our 5 unpublished cases): 49 (83%) patients were female and 10 (17%) were male, with a mean age at diagnosis of 50 years. According to the histopathologic examination of the exocrine glands performed in 53 cases, we defined coexistence of sarcoidosis and SS in 28 cases, while in the remaining 25 patients, sarcoidosis mimicked SS. Clues to identifying when sarcoidosis coexists with SS were a higher prevalence of systemic manifestations (arthritis and uveitis) and positive immunologic parameters (antinuclear antibodies, rheumatoid factor, and anti-Ro/SS-A), as well as the existence of a focal sialadenitis (Chisholm-Mason score grades III-IV, with a CD4+ lymphocytic infiltration) in the salivary gland biopsy. In patients first diagnosed with primary SS, the appearance of some clinical features such as hilar adenopathies, uveitis, or hypercalcemia leads to the diagnosis of coexisting sarcoidosis. A careful application of the new American-European consensus criteria had a sensitivity of 93% and a specificity of 92% in identifying when SS coexists with sarcoidosis.In conclusion, the association of sarcoidosis with SS leads to a true coexistence of both diseases in more than half the patients described in the literature, while in the remaining patients, sarcoidosis mimics SS. In light of these results, sarcoidosis should not be considered as an exclusion criterion for the diagnosis of SS, and in patients with a suspected overlap of the two diseases, application of the new American-European consensus criteria for diagnosis of SS should be mandatory.

Ramos-Casals M, García-Carrasco M, Brito Zerón MP, Cervera R, Font J. · Department of Autoimmune Diseases, C/Villaroel 170, Hospital Clínic, Institut Clínic d'Infeccions i Immunologia, 08036 Barcelona, Catalonia, Spain. · Autoimmun Rev. · Pubmed #12849002 No free full text.

Abstract: Patients with hepatitis C virus (HCV) chronic infection present some extrahepatic manifestations that may mimic the clinical, immunologic and histological manifestations of primary Sjögren's syndrome (SS). Thus, HCV patients with sicca symptomatology and positive autoantibodies could be misdiagnosed as a 'primary' SS. Nevertheless, there are several clinical and immunologic features that could help us differentiate both processes.

Ramos-Casals M, Trejo O, García-Carrasco M, Font J. · Department of Autoimmune Diseases, Clinical Institutes of Infection and Immunology, Insitut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Department of Medicine, School of Medicine, University of Barcelona, Spain. · Rheumatology (Oxford). · Pubmed #12730523 links to  free full text

This publication has no abstract.

García-Carrasco M, Ramos-Casals M, Rosas J, Pallarés L, Calvo-Alen J, Cervera R, Font J, Ingelmo M. · Department of Autoimmune Diseases, Clinical Institute of Infections and Immunology, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #12169882 No free full text.

This publication has no abstract.

García-Carrasco M, Font Franco J, Ingelmo Morín M, Ramos-Casals M. · Servicio de Enfermedades Autoinmunes, Hospital Clínic,Barcelona, Spain. · Rev Clin Esp. · Pubmed #12003734 No free full text.

This publication has no abstract.

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.

García-Carrasco M, Ramos-Casals M, Cervera R, Font J. · Unitat de Malalties Autoimmunes Sistèmiques, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona. · Med Clin (Barc). · Pubmed #10919130 No free full text.

This publication has no abstract.

Ramos-Casals M, Trejo O, García-Carrasco M, Cervera R, Font J. · Department of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, School of Medicine, University of Barcelona, Catalonia, Spain. · Lupus. · Pubmed #10787003 No free full text.

Abstract: The most documented extrahepatic manifestation of hepatitis C virus (HCV) infection is mixed cryoglobulinemia (MC). MC is characterised by the presence of temperature-sensitive protein complexes: in type II MC, cryoglobulins are composed of a monoclonal rheumatoid factor (usually, IgMkappa) against polyclonal IgG. In type III MC, all components are polyclonal. The presence of microheterogeneity and other new types of cryoglobulins is a novel and recent observation. The production of different autoantibodies and circulating immune complexes, including the cryoglobulins, are responsible for systemic vasculitis and various organ damage. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop. Finally, results of interferon and/or ribavirin treatments in MC patients represent an indirect proof for the pathogenetic link between MC and HVC infection. The discovery of the relation between HCV infection and MC shows the striking association between a viral infection and an autoimmune disease and, thus, a potential link between the systemic autoimmune and lymphoproliferative disorders.

Ramos-Casals M, García-Carrasco M, Cervera R, Font J. · Systemic Autoimmune Diseases Unit, Hospital Clínic, Barcelona, Catalonia, Spain. · Clin Rheumatol. · Pubmed #10357112 No free full text.

Abstract: Sjögren's Syndrome (SS) is an autoimmune disease that mainly affects exocrine glands and usually presents as a persistent dryness of the mouth and eyes. The spectrum of the disease extends from an organ-specific autoimmune disease to a systemic process. Viral infection has long been suspected as a potential cause of SS because several viruses have been incriminated in the aetiology of this disease, and a possible relationship between SS and hepatitis C virus (HCV) was postulated in 1992. In this paper, we review the literature concerning SS and HCV infection and summarise the current knowledge regarding their association and their pathogenic, clinical and immunological significances. The main conclusions of this review are that the prevalence of antibodies to HCV in patients with primary SS ranges between 14 and 19% using third-generation ELISA, chronic HCV infection may mimic the main clinical, histological and immunologic features of 'primary' SS and, finally, testing for HCV infection must be performed in patients with SS, especially in those patients with evidence of liver involvement or associated cryoglobulinaemia. HCV seems to be a rare cause of 'primary' SS in the absence of recognised liver disease or cryoglobulinaemia.

Rosas J, Ramos-Casals M, Ena J, García-Carrasco M, Verdu J, Cervera R, Font J, Caballero O, Ingelmo M, Pascual E. · Rheumatology Unit, Hospital of Vila-Joiosa, Alicante, Spain. · Rheumatology (Oxford). · Pubmed #12048294 links to  free full text

Abstract: OBJECTIVES: To examine salivary function in patients with primary Sjögren's syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5% solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. METHODS: We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated (basal) salivary flow (BSF) in all patients. In patients with BSF </=1.5 ml, stimulated salivary flows (SSF) were also measured after stimulation with an ophthalmic 5% pilocarpine solution (0.1 ml=5 mg, administered sublingually). SSF was also measured after oral administration of 50 mg anetholetrithione (ANTT) in the same patients. These stimulated salivary flows were measured 1, 2 and 3 h after the stimulus. RESULTS: Of the 60 patients, 55 were women and five men, with a mean age at the SS onset of 61 yr (range 18-82 yr). The mean BSF for SS patients was 1.40+/-0.17 ml. Fifty (83%) patients showed a BSF less than 1.5 ml. The stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57 in the ANTT group (P<0.001); after 2 h it was 1.32 ml in the pilocarpine group and 0.52 in the ANTT group (P=0.02) and after 3 h it was 0.80 ml in the pilocarpine group and 0.41 in the ANTT group (P=0.046). No clinical or immunological differences were found between SS patients with BSF more or less than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid scintigraphy class III or IV more frequently (42 vs 0%, P=0.01). SS patients with a pilocarpine SSF less than 1.5 ml had a longer duration of SS (73.3 vs 31.3 months, P=0.03) and a higher prevalence of positive anti-Ro/SS-A (70 vs 36%, P=0.038), anti-La/SS-B (65 vs 32%, P=0.038), parotid scintigraphy class III-IV (79 vs 9%, P<0.001) and positive salivary gland biopsy (90 vs 43%, P<0.001). CONCLUSION: The study of xerostomia using basal and pilocarpine SSF is simple to perform, acceptable to patients and needs no special equipment. We describe a significant increase in SSF using a solution of 5% pilocarpine in comparison with salivary flow obtained after stimulation with ANTT. Twenty-two of the 46 patients with low BSF had stimulated flows over 1.5 ml. These 'responder' patients showed a shorter duration of sicca symptoms, a lower frequency of positive immunological markers and milder grades of scintigraphic patterns and lymphocytic infiltrates in salivary gland biopsies. This subset of patients probably maintain a residual capacity of their salivary glands, as opposed to the 'non-responder' patients, who had a longer duration of sicca syndrome evolution with more severe involvement of the salivary glands.

García-Carrasco M, Fuentes-Alexandro S, Escárcega RO, Rojas-Rodriguez J, Escobar LE. · Systemic Autoimmune Diseases Research Unit, HGZ #36, CMN Manuel Avila Camacho, Instituto Mexicano del Seguro Social, Puebla, Mexico. · Joint Bone Spine. · Pubmed #17706449 No free full text.

Abstract: Thalidomide is an immunomodulating agent which reverses many of the cytokine disturbances seen in systemic onset juvenile idiopathic arthritis (SoJIA) with inadequate response to other treatments. We report 3 cases of recalcitrant SoJIA which improved dramatically after treatment with thalidomide. PATIENTS: Three children aged 9, 8, and 6 years diagnosed with SoJIA treated with conventional therapy including NSAIDs, corticosteroids, methotrexate and etanercept failed to respond fully and their condition worsened. Thalidomide was begun based on two previous reports showing its efficacy in recalcitrant SoJIA. RESULTS: Thalidomide produced successful remission of the disease in all 3 patients according to the preliminary criteria for inactive disease and clinical remission of JIA. CONCLUSION: Thalidomide may be a viable, alternative corticoid-sparing therapy in patients with recalcitrant, multidrug-resistant SoJIA.

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.

Trejo O, Ramos-Casals M, López-Guillermo A, García-Carrasco M, Yagüe J, Cervera R, Font J, Ingelmo M. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain. · Semin Arthritis Rheum. · Pubmed #12920693 No free full text.

Abstract: OBJECTIVE: To determine the prevalence and clinical characteristics of hematologic malignancies occurring in a large series of patients diagnosed with cryoglobulinemia, and to study their association and overlap with autoimmune and/or chronic viral diseases. METHODS: We retrospectively analyzed the occurrence of hematologic malignancies in 607 patients diagnosed with cryoglobulinemia in a single institution. Clinical, histologic, and serologic characteristics of patients were recorded on a protocol form. Hematologic malignancies were diagnosed according to the Revised European-American Lymphoma/World Health Organization classification criteria. RESULTS: Of the total cohort of 607 patients with cryoglobulinemia, we retrospectively identified 27 patients (5%) in whom a hematologic malignancy was diagnosed, including 24 (89%) lymphoproliferative and 3 (11%) myeloid malignancies. Fifteen (56%) were men and 12 (44%) women, with a median age at diagnosis of hematologic malignancy of 67 years (range, 44 to 88 years). The identified hematologic malignancies were non-Hodgkin lymphoma (n = 18), Hodgkin lymphoma (n = 2), chronic lymphocytic leukemia (n = 2), and 1 case each of multiple myeloma, Waldenström macroglobulinemia, Castleman disease, chronic myeloid leukemia and myelodysplastic syndrome. Of the 18 patients with non-Hodgkin lymphoma, there was a predilection for specific histologic types (diffuse large B-cell lymphoma in 8 cases and small lymphocytic lymphoma in 4) and a higher frequency of a primary extranodal origin in 6 (33%) cases. Conditions associated with hematologic malignancies were hepatitis C virus (HCV) infection in 14 patients (52%) and systemic autoimmune diseases in 13 (48%), with both HCV and systemic autoimmune disease in 6 cases (22%). CONCLUSIONS: Hematologic neoplasia associated with cryoglobulinemia is defined by a clear predominance of lymphoproliferative disorders (mainly non-Hodgkin lymphoma), with substantial extranodal involvement and an elevated presence of immunologic markers. HCV infection is the main etiologic factor associated with hematologic malignancies in patients with cryoglobulinemia, followed by specific systemic autoimmune diseases such as Sjögren syndrome and systemic lupus erythematosus, highlighting the close relationship between lymphoproliferation, autoimmunity, and viruses.

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.

Cervera R, Viñas O, Ramos-Casals M, Font J, García-Carrasco M, Sisó A, Ramírez F, Machuca Y, Vives J, Ingelmo M, Burlingame RW. · Department of Autoimmune Diseases, Institut Clínic d'Infeccions i Immunologia, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer, Barcelona, Catalonia, Spain. · Ann Rheum Dis. · Pubmed #12695155 links to  free full text

Abstract: BACKGROUND: Anti-chromatin antibodies have recently been described in patients with systemic lupus erythematosus (SLE) and it has been suggested that their presence is associated with lupus nephritis. OBJECTIVE: To assess the prevalence and clinical associations of these antibodies in SLE. METHODS: The presence of anti-chromatin antibodies in 100 patients with SLE was investigated by an enzyme linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 100 patients with primary Sjögren's syndrome, 30 with primary antiphospholipid syndrome (APS), 10 with systemic sclerosis, and 100 normal controls were also tested. RESULTS: Positive levels were detected in 69/100 (69%) patients with SLE. In contrast, they were found in only 8/100 (8%) of those with primary Sjögren's syndrome, in 1/10 (10%) with systemic sclerosis, in 2/30 (7%) with primary APS, and in none of the 100 healthy controls. Patients with anti-chromatin antibodies had a twofold higher prevalence of lupus nephropathy than those without these antibodies (58% v 29%, p<0.01). A significant correlation was found between the levels of anti-chromatin antibodies and disease activity score as measured by the European Consensus Lupus Activity Measurement (ECLAM; p=0.011). CONCLUSIONS: The measurement of anti-chromatin antibodies appears to be a useful addition to the laboratory tests that can help in the diagnosis and treatment of SLE. These antibodies are both sensitive and specific for SLE, and are a useful marker for an increased risk of lupus nephritis.

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.

Font J, García-Carrasco M, Ramos-Casals M, Aldea AI, Cervera R, Ingelmo M, Vives J, Yagüe J. · Systemic Autoimmune Diseases Unit, Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain. · Rheumatology (Oxford). · Pubmed #12209037 links to  free full text

Abstract: OBJECTIVE: To analyse the role of polymorphisms of the interleukin-10 promoter region in the epidemiologic, clinical and immunologic characteristics of patients with primary Sjögren's syndrome (SS). METHODS: Sixty-three consecutive patients (59 women and four men; mean age 57 yr; range 20-83 yr) were studied in our Unit. All patients fulfilled four or more of the modified diagnostic criteria for SS proposed by the European Community Study Group in 1996. As controls, 150 healthy volunteers were recruited from the medical and laboratory staff working in our hospital. All the samples from patients and controls were analysed by PCR amplification and direct sequencing. RESULTS: The frequency of the interleukin-10 (IL-10) GCC haplotype was higher (0.48 vs 0.34, P=0.006) and the frequency of the IL-10 ACC haplotype lower (0.25 vs 0.39, P=0.005) in patients with primary SS compared with healthy controls. In the genotype analysis, the frequency of the GCC/ATA genotype was higher (29 vs 11%, P=0.001) and that of the ACC/ACC genotype lower (3 vs 12%, P=0.044) in patients with primary SS compared with healthy controls. GCC-carriers showed an earlier onset of the disease (48.06+/-14.98 yr vs 57.53+/-14.20 yr, P=0.034). The existence of systemic involvement (defined by cutaneous vasculitis, peripheral neuropathy, renal and/or pulmonary involvement) was more frequent in carriers of the GCC haplotype, although the difference did not reach statistical significance (40 vs 27%, P=0.278). No significant differences in the haematologic (hypergammaglobulinaemia, elevated ESR) and immunologic (ANA, RF, anti-Ro/SS-A and anti-La/SS-B antibodies) parameters were observed in carriers of the GCC haplotype. CONCLUSION: We describe an abnormal distribution of IL-10 promoter haplotypes in patients with primary SS compared with healthy controls. This consists of a predominance of the GCC haplotype, mainly related to a higher frequency of the heterozygote haplotype GCC/ATA. The presence of the GCC haplotype does not originate a different immunologic pattern but leads to an earlier onset of primary SS.

García-Carrasco M, Sisó A, Ramos-Casals M, Rosas J, de la Red G, Gil V, Lasterra S, Cervera R, Font J, Ingelmo M. · Department of Systemic Autoimmune Diseases, Hospital Clinic, Barcelona, Spain. · J Rheumatol. · Pubmed #11950013 No free full text.

Abstract: OBJECTIVE: To determine the prevalence of Raynaud's phenomenon (RP) in a large series of patients with primary Sjögren's syndrome (SS) and to identify the clinical and immunological features related to its presence. METHODS: In a cross sectional study, we investigated 320 consecutive patients with primary SS (294 women, 26 men; mean age at onset 60 yrs, range 16-87 yrs). All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Diagnosis of RP in patients with SS was defined as intermittent attacks of digital pallor and/or cyanosis in the absence of any other associated disease or anatomical abnormalities. RESULTS: RP was present in 40 (13%) patients. All were women, with a mean age of 57 yrs (range 18-78). RP preceded onset of sicca symptomatology in 18 (45%) patients. The main triggering factor was exposure to cold, which induced RP in all patients, while emotional stress was a factor in 12 patients, as was job related predisposition in 2. Fifteen (38%) patients required pharmacological treatment with calcium channel blockers (12 patients) or angiotensin converting enzyme inhibitors (2 patients) during colder months, and one patient required treatment with intravenous prostacyclin for ischemic complications. Compared with SS patients without RP, those with RP showed a higher prevalence of articular involvement (50 vs 31%; p = 0.031), cutaneous vasculitis (30 vs 11%; p = 0.003), antinuclear antibodies (95 vs 65%; p < 0.001), anti-Ro/SSA (59 vs 31%; p < 0.001) and anti-La/SSB antibodies (44 vs 20%, p = 0.003). CONCLUSION: We found RP in 13% of patients with primary SS, in almost half of whom RP was the first autoimmune symptomatology. These patients constituted a subset of SS with a higher frequency of some extraglandular features and positive immunological markers. The clinical course of RP seems to be milder in patients with primary SS than in those with other systemic autoimmune diseases such as systemic sclerosis, with no vascular complications and pharmacological treatment needed in only 40% of patients.

Ramos-Casals M, Font J, García-Carrasco M, Calvo J, Places L, Padilla O, Cervera R, Bowen MA, Lozano F, Ingelmo M. · Systemic Autoimmune Diseases Unit and. Department of Immunology, Hospital Clínic, Department of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain. · Rheumatology (Oxford). · Pubmed #11561119 links to  free full text

Abstract: OBJECTIVE: To determine the existence of circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren's syndrome (SS), and to analyse the correlation with clinical and immunological features of SS. METHODS: Ninety consecutive patients with primary SS were studied. All patients fulfilled four or more of the European diagnostic criteria for SS. sCD5 and sCD6 levels were determined using a specific enzyme-linked immunosorbent assay (ELISA) developed in our laboratory. RESULTS: Detectable levels of sCD5 were found in 39 (43%) SS patients. The mean+/-standard error values of sCD5 were 3.5+/-0.5 ng/ml for patients with SS and 1.9+/-0.1 ng/ml for healthy blood donors (P<0.001). We found higher levels of sCD5 in patients with hypocomplementaemia (6.5 vs 3.5 ng/ml, P=0.03) and cryoglobulinaemia (6.9 vs 2.6 ng/ml, P=0.001). On the other hand, detectable levels of sCD6 were found in 60 (67%) SS patients. The mean+/-standard error values of sCD6 were 25.5+/-7.8 ng/ml in SS patients and 5.27+/-1.40 ng/ml in healthy blood donors (P=0.01). When the sCD6 levels were compared according to the presence or absence of immunological features, patients with cryoglobulinaemia showed higher levels of circulating sCD6 (77.3 vs 17 ng/ml, P=0.01) than those without cryoglobulinaemia. CONCLUSION: Patients with primary SS showed higher levels of circulating sCD5 and sCD6 when compared with controls. Moreover, the existence of some immunological features (hypocomplementaemia and cryoglobulinaemia) was associated with high levels of both soluble scavenger receptors. These facts may reflect an enhanced lymphocytic activation in patients with primary SS.

Ramos-Casals M, Cervera R, García-Carrasco M, Vidal J, Trejo O, Jiménez S, Costa J, Font J, Ingelmo M. · Department of Microbiology, Institut d'Investigaciones Biomèdiques August Pi I Sunyer IDIBAPS, Hospital Clínic, School of Medicine, University of Barcelona, Spain. · Semin Arthritis Rheum. · Pubmed #10924023 No free full text.

Abstract: OBJECTIVES: To determine the clinical significance of human parvovirus B19 infection in patients with primary Sjögren's syndrome (SS) and to investigate the immunologic and hematologic features related to B19 infection. METHODS: We included 80 consecutive patients with primary SS (74 women and 6 men), with a mean age of 62 years (range, 24 to 87 years) that were seen in our Unit. All patients fulfilled the European Community criteria for SS. As controls, we included 140 consecutive sera samples analyzed for B19 antibodies in our Microbiology Department and obtained from adult inpatients and outpatients of our Hospital. Serum from all patients and controls was tested for antibodies to B19 by enzyme-linked immunosorbent assay (ELISA). Additionally, the presence of B19 DNA in serum and in circulating leukocytes was investigated by nested polymerase chain reaction (PCR). RESULTS: Serological evidence of past B19 infection (positive IgG antibodies without IgM antibodies) was present in 28 (35%) patients with primary SS. None of these patients showed evidence for B19 viremia, and B19 virus DNA was not detected in the circulating leukocytes of IgG-B19(+) patients. Positivity for IgM antibodies to B19 was not detected in any patient. When compared with patients without evidence of past B19 infection, those with primary SS and past B19 infection showed a higher prevalence of cytopenia (57% v 15%; P < .001), and, specifically, of leukopenia (36% v 4%; P < .001). Additionally, when compared with controls positive for IgG-B19, SS patients with these antibodies had a higher prevalence of cytopenia (57% v 13%; P < .001), leukopenia (36% v 3%; P < .001) and thrombocytopenia (21% v 0%; P = .003). CONCLUSIONS: Serological evidence of past B19 infection is associated with the presence of cytopenia in our patients with primary SS. A possible relationship between B19 infection and the presence of cytopenia in primary SS may occur in some patients immunologically or genetically predisposed.

Ramos-Casals M, García-Carrasco M, Cervera R, Gaya J, Halperin I, Ubieto I, Aymamí A, Morlà RM, Font J, Ingelmo M. · Systemic Autoimmune Diseases Unit, Hospital Clínic, School of Medicine, University of Barcelona, Spain. · Medicine (Baltimore). · Pubmed #10771708 No free full text.

Abstract: We studied 160 consecutive patients (147 female and 13 male) with primary Sjögren syndrome (SS) to determine the prevalence and clinical significance of thyroid disease in a large series of patients with primary SS from our unit and to compare the prevalence and significance with those in 75 individuals without SS from a primary care center. Serum levels of thyroid hormones (free thyroxine, triiodothyronine, and thyroid-stimulating hormone) and autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) were measured in all SS patients and in 75 control patients. Fifty-eight (36%) of the 160 patients with primary SS had evidence of thyroid disease. Autoimmune thyroid disease (ATD) was diagnosed in 32 (20%) patients and nonautoimmune thyroid disease (NATD) in 26 (16%). No significant differences were found when these prevalences were compared with those in control patients. On the other hand, comparing those patients with altered hormonal profiles, patients with NATD showed mainly hyperthyroidism (10/17, 59% versus 2/20, 10% in patients with ATD, p = 0.001). Finally, when clinical and immunologic manifestations of SS were analyzed in patients with and without thyroid disease, respectively, we found that patients with thyroid disease had a higher prevalence of female gender (98% versus 88%, p = 0.03), antiparietal cell autoantibodies (33% versus 12%, p = 0.002), TgAb (30% versus 5%, p < 0.001), and TPOAb (40% versus 5%, p < 0.001). In conclusion, thyroid disease occurred in more than one-third of patients with primary SS; the main cause was ATD, which was present in 20% of the patients studied. We note that no significant differences were observed when the prevalence of thyroid disease (either ATD or NATD) was compared with that in a control group of similar age and gender. Our results indicate that middle-aged women (with or without SS) should be screened periodically for thyroid function.