Manuel Ramos-Casals

Institut Marqués, Spain, Barcelona, Barcino, Catalonia, Spain

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Publications (272)1517.1 Total impact

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    ABSTRACT: Introduction We conducted a study to analyze how infection by hepatitis C virus (HCV) may influence the immunological serum pattern of patients with Sjögren syndrome (SS). Methods Since 1994, we have tested serum HCV-IgG antibodies in 783 patients with SS diagnosed according to the 1993 European classification criteria. The immunological profile at diagnosis was compared according to the presence or absence of HCV. Results Of the 783 patients with SS, 105 (13.4 %) tested positive for HCV-IgG antibodies (88 females, 17 males, mean age at SS diagnosis: 62.9 years). Multivariate analysis showed that patients with SS-HCV had a higher mean age and a higher frequency of low C3/C4 levels, cryoglobulins, and hematological neoplasia compared with patients without HCV. The frequency of anti-La antibodies compared with anti-Ro antibodies was higher in patients with SS-HCV (17 % vs. 15 %) and lower in patients without HCV infection (30 % vs. 43 %). The frequency of concomitant detection of the three main cryoglobulin-related markers (cryoglobulins, rheumatoid factor activity, and C4 consumption) was threefold higher in patients with SS-HCV compared with patients without HCV. SS-HCV patients with genotype 1b showed the highest frequencies of immunological abnormalities related to cryoglobulins and the lowest frequencies of anti-Ro/La antibodies. Conclusions We found HCV infection in 13 % of a large series of Spanish patients with SS. The HCV-driven autoimmune response was characterized by a lower frequency of anti-Ro/La antibodies, an abnormal predominance of anti-La among anti-Ro antibodies, and a higher frequency of cryoglobulinemic-related immunological markers in comparison with patients without HCV infection. This immunological pattern may contribute to the poor outcomes found in patients with SS-HCV.
    Arthritis Research & Therapy 12/2015; 17(1). DOI:10.1186/s13075-015-0766-3 · 3.75 Impact Factor
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    ABSTRACT: Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.
    Medicine 10/2015; 94(43):e1728. DOI:10.1097/MD.0000000000001728 · 5.72 Impact Factor
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    ABSTRACT: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
    Rheumatology (Oxford, England) 09/2015; DOI:10.1093/rheumatology/kev311 · 4.48 Impact Factor
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    ABSTRACT: Background and aims: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. Results: We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point). Conclusions: Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
    Annals of the rheumatic diseases 09/2015; 74(9). DOI:10.1136/annrheumdis-2013-205171 · 10.38 Impact Factor
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    ABSTRACT: Objective: To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS. Methods: The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features. Results: The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ. Conclusion: The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.
    Rheumatology (Oxford, England) 07/2015; DOI:10.1093/rheumatology/kev200 · 4.48 Impact Factor
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    ABSTRACT: Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic pathway leading to organ damage: an excessive inflammatory response. Biological therapies have been proposed as a therapeutic option for refractory HLH, but have also been related to the development of HLH in severe immunosuppressed patients. The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies. We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents (n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis (n = 5), cytomegalovirus (CMV) (n = 4), Epstein-Barr virus (EBV) (n = 3), Histoplasma capsulatum (n = 3), Escherichia coli (n = 2), Staphylococcus aureus, Leishmania amastigotes and Brucella melitensis (n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies (p = 0.036) and had lower leukocyte counts (p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively). In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended. Copyright © 2015 Elsevier Inc. All rights reserved.
    Seminars in arthritis and rheumatism 07/2015; DOI:10.1016/j.semarthrit.2015.07.004 · 3.93 Impact Factor
  • John H Stone · Pilar Brito-Zerón · Xavier Bosch · Manuel Ramos-Casals ·
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    ABSTRACT: IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
    Mayo Clinic Proceedings 07/2015; 90(7):927-39. DOI:10.1016/j.mayocp.2015.03.020 · 6.26 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):578.1-578. DOI:10.1136/annrheumdis-2015-eular.4783 · 10.38 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):102.2-102. DOI:10.1136/annrheumdis-2015-eular.4035 · 10.38 Impact Factor
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    ABSTRACT: Objectives To evaluate extrapulmonary activity and correlate baseline features at diagnosis with survival in a large cohort of patients with sarcoidosis. Methods We studied 170 patients consecutively diagnosed with sarcoidosis in the last 10 years. The diagnosis of sarcoidosis was based on clinical criteria and imaging studies, together with the histopathological demonstration of non-necrotizing granulomas, and the exclusion of other granulomatous diseases, especially infections (tuberculosis). Extrapulmonary involvement was defined according to the criteria defined by Judson et al, 2011. Results There were 111 (65%) women and 59 (35%) men, with a mean age at diagnosis of 47.49 years (range 17-92). The main clinical manifestations present at diagnosis were respiratory symptoms in 112 (66%) patients, erythema nodosum in 35 (21%), articular involvement in 35 (21%) and fever in 34 (20%) patients; incidental imaging findings in asymptomatic patients was found in 12% of cases. After a mean follow-up of 107.4 months, 21 (12%) patients died. The main causes of death were infections in 4 patients, cardiovascular disease in 2, pulmonary sarcoidosis in 1, neoplasia in 1 and other causes in 2 patients; in the remaining 11 patients, the cause of death was unknown or unclassifiable. Survivors had a lower mean age (44.82 yrs. vs. 65.95 yrs. p<0.001) and a statistical trend to higher mean levels of serum angiotensin-converting enzyme (ACE) (105.78 U/L vs. 64.58 U/L, p=0.16). The mortality rate was higher in patients born in Spain (16% vs. 0% in those born outside Spain, p=0.008). Extrapulmonary involvement was unrelated to death (mortality rate of 11% vs. 14% in patients with pulmonary involvement). Multivariate analysis identified mean age at diagnosis (p<0.001) as an independent risk factor associated with death. Conclusions Extrapulmonary involvement in sarcoidosis is not associated with mortality. An older age at diagnosis was the principal risk factor associated with death, while patients born outside Spain had a lower mortality rate, and mean ACE levels at diagnosis were inversely associated with survival. The very-low rate of deaths caused directly by sarcoidosis might explain our results. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):404.3-405. DOI:10.1136/annrheumdis-2015-eular.3357 · 10.38 Impact Factor
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    ABSTRACT: Objectives To analyse the epidemiological, clinical and analytical features at diagnosis and the use of the European systemic activity index (ESSDAI) to predict the development of cancer in a large cohort of Spanish patients with primary Sjogren syndrome (SS). Methods The GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included thirteen Spanish reference centers with substantial experience in the management of SS patients. By January 2015, the database included 1216 consecutive patients fulfilling the 2002 classification criteria for primary SS. ESSDAI scores were retrospectively calculated at diagnosis. Disease activity states (DAS) were defined according to the baseline ESSDAI score (low DAS for an ESSDAI <4, moderate DAS for an ESSDAI between 5 and 13, and high DAS for an ESSDAI higher than 13). Cancer was categorized as hematological or solid neoplasia. Results After a mean follow-up of 114 months, 84 (7%) patients developed solid cancer and 52 (4%) hematological neoplasia. The following baseline features at diagnosis were associated with the development of hematological neoplasia: male gender (19% vs 6%, p<0.001), age at diagnosis (59 vs 54 yrs, p<0.001), baseline systemic activity (75% vs 51%, p=0.001), neutropenia (19% vs 9%, p=0.028), C3 values <0.82 g/L (19% vs 10%, p=0.048), C4 values <0.07 g/L (24% vs 12%, p=0.02), monoclonal serum band (27% vs 8%, p<0.001) and cryoglobulins (30% vs 9%, p<0.001). In contrast, only age (59 vs 54 yrs, p<0.001) and neutropenia (21% vs 9%, p=0.001) were related to the development of solid neoplasia. High systemic activity (high-DAS) was found in a higher frequency in patients who developed hematological in comparison with those who developed solid neoplasia or those without neoplasia (79% vs 24% vs 21%, p<0.001). Conclusions Systemic and biological activity is closely related to the development of lymphoma in primary SS. Etiopathogenic factors such as B-cell hyperactivity and monoclonal, cryoglobulinemic-driven immunological responses have a dual effect, enhancing the risk of development of both systemic involvement and hematological neoplasia, but not the risk of solid neoplasia, whose development is independent of systemic Sjögren. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):810.2-810. DOI:10.1136/annrheumdis-2015-eular.3796 · 10.38 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):102.1-102. DOI:10.1136/annrheumdis-2015-eular.3946 · 10.38 Impact Factor
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    ABSTRACT: Background Serum cryoglobulins (SC) may be found in many diseases (1), and the presence of serum cryoglobulins is a known risk factor for lymphoma evolution in some non malignant diseases. Objectives The aim of this study was to distiguish the role of cryoglobulinemic vasculitis (CV), classified according to the recent validated criteria (1,2), and primary Sjögren's syndrome (pSS) as risk factors of lymphoma in patients positive serum cryoglobulins. Importantly, SC, CV and pSS may occur together. Methods 950 charts from consecutive patients with positive SC were evaluated. Patients carrying both pSS and HCV infection, as well as incomplete charts, were excluded. Results 657 patients with SC were selected, 374 with CV and 283 without CV, according to the published criteria (2,3). PSS, classified according to the American-European Group Criteria was present in 96 patients (44 with CV, 52 without). Lymphoma was reported in 61/657 (9.8%) patients with SC. Among them, CV was present in 44/61 (72,1%; 14 also with pSS), and pSS in 17/61 (27,9%; and 14/17 had CV). Patients with SC with CV showed an higher prevalence of lymphoma than patients with SC without CV (44/374, 11.5% vs.17/283, 6.3%; p=0.025, OR=1.93 [95%IC: 1.08-3.39]. Patients with pSS, SC and CV also showed a higher prevalence of lymphoma than patients with pSS, SC but without CV (14/44, 31.8% vs. 3/52, 7.4%; p=0.001, OR=7.62 [95%CI 2.02-28.74]. CV and pSS were confirmed as independent risk factor for lymphoma by multivariate analysis (OR 2,18 95%CI 1,18-3,83, p=0,012; OR 2,65 95%CI 1,04-6,76, p=0,042, respectively). Infection by the hepatitis C virus (HCV) was detected in 467/561 (83,2%) patients with SC without pSS, and did not statistically predispose to lymphoma when associated with CV in this subset (p=1,0). Conclusions Cryoglobulinemic vasculitis and pSS are independent risk factors for lymphoma in patients with evidence of SC. Patients with both the conditions (CV and pSS) have the highest risk. In the follow-up of SC positive patients, a very high attention should be deserved to pSS, in particular when CV is present. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):175.3-176. DOI:10.1136/annrheumdis-2015-eular.3300 · 10.38 Impact Factor
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    ABSTRACT: Objectives To characterize and quantify systemic involvement at diagnosisinalarge international cohort of patients diagnosed with primary Sjogren syndrome (SS). Methods The Big Data Sjögren Project is an international, multicenter registry formed in 2014 with the aim of taking a “high-definition” picture of the main features of primary SS at diagnosis by merging international SS databases. By January 2015, the database included 5027 consecutive patients fulfilling the 2002 classification criteria for primary SS from 13 countries (9 European, 4 American). Systemic involvement was defined according to the ESSDAI and retrospectively calculated. Results Baseline ESSDAI data was collected in3314 patients (94% female, mean age at diagnosis 54.25 years). The main features of systemic involvement at diagnosis included biological activity in 43%of patients, articular involvement in 35%, hematological activity in 25%and glandular involvementin 19%. The mean ESSDAI score at diagnosis of the entire cohort was 5.63 (range, 0-62). Low DAS was reported in 1267 (38%) patients, moderate DASin 943 (28%) and high DAS in 378 (11%) patients; in the remaining 726 patients (22%), the ESSDAI score at diagnosis was 0. The mean baseline ESSDAI was higher in males (7.33 vs 5.52, p<0.001), patients diagnosed ≤35 years (6.71 vs 5.63, p=0.001), those with positive ocular tests (5.75 vs 4.98, p=0.023) and those with positive immunological markers including ANA (6.71 vs 4.63, p<0.001), RF (7.46 vs 5.49, p<0.001), anti-Ro/SSA (6.77 vs 5.48, p<0.001) and anti-La/SSB (6.91 vs 6.0, p<0.001). According to the number of criteria fulfilled at diagnosis, a higher mean baseline ESSDAI was found in patients fulfilling the six criteria (7.67 vs 5.65 in those fulfilling 5 criteria and 5.23 in those fulfilling 3-4 criteria, p<0.001). Conclusions Epidemiological features (male sex, younger age at diagnosis) and positive autoantibodies at diagnosis were closely-related to greater systemic activity. Using the ESSDAI in real-life situations may help identify epidemiological and immunological subsets with high systemic activity at diagnosis and, therefore, at high risk of suffering a complicated clinical course. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):578.2-578. DOI:10.1136/annrheumdis-2015-eular.4752 · 10.38 Impact Factor
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    ABSTRACT: Background Antimitochondrial antibodies (AMA) are autoantibodies directed against proteins of the outer and inner mitochondrial membrane. M2 antibodies stand out because of their high sensitivity and specificity for the identification of primary biliary cirrhosis. Objectives To analyse the prevalence of AMA and M2 autoantibodies in a large cohort of Spanish patients with primary Sjogren syndrome (SS), and to correlate positive results with epidemiological, clinical and immunological expression of the disease. Methods The GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS. The cumulated ESSDAI index (2010 EULAR-SS disease activity index) was retrospectively calculated at diagnosis. AMA were detected by indirect immunofluorescence in triple rat tissue and M2 autoantibodies by ELISA against M2 proteins (PDC-E2, BCOADC-E2, OGDC-E2). Results AMA were tested consecutively in 733 patients with primary SS (688 women, mean age at diagnosis of 54.65 yrs), of whom 63 (9%) showed positive results. No significant differences were found in the main epidemiological, clinical and immunological features according to the presence or absence of AMA, except for a higher frequency of anti-Ro/SSA antibodies (83% vs 68%, p=0.015) and leucopenia (33% vs 21%, p=0.038) in AMA+ patients in comparison with those with negative AMA. M2 autoantibodies were tested in 210 patients, of whom 19 (9%) were positive. Comparison of the main epidemiological, clinical and immunological features according to the presence or absence of anti-M2 antibodies showed a higher frequency of anti-Ro/SSA antibodies (95% vs 74%, p=0.049), leucopenia (53% vs 19%, p=0.002), neutropenia (48% vs 22%, p=0.025), low C4 levels (26% vs 6%, p=0.008) and biological activity measured by the ESSDAI (84% vs 50%, p=0.007). We have the paired determination of AMA and anti-M2 in 23 patients with positive results: 12 have concordant positive results and 11 discordant (7 had negative AMA with positive M2, and 4 positive AMA with negative M2). The mean value of M2 autoantibodies in AMA+ patients was twice than in those with negative AMA, although the difference was not statistically significant (85.67 vs 41.51, p=0.126). Conclusions The study showed three key messages: i) the prevalence of AMA/M2 in primary SS was of 9%; ii) AMA/M2 correlated with the coexistence of Ro autoantibodies but not with systemic Sjögren; and iii) nearly half the patients showed discordant results between AMA and M2 positivities. We recommend the use of M2-ELISA to test for AMA in patients with primary SS. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):647.1-647. DOI:10.1136/annrheumdis-2015-eular.3961 · 10.38 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):579.1-579. DOI:10.1136/annrheumdis-2015-eular.5236 · 10.38 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):858.1-858. DOI:10.1136/annrheumdis-2015-eular.4864 · 10.38 Impact Factor
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    ABSTRACT: Background HScore is a numeric scoring system recently proposed by Fardet et al in 2014, designed to estimate the risk of having hemophagocytic syndrome (HS) in adults. Objectives The objective of this study is to analyze the potential use of the HScore as a prognostic factor in a large cohort of Spanish patients with adult HS. Methods In June 2013, the Study Group of Autoimmune Diseases (GEAS-SEMI) created the National Registry of Adult Patients with HS. Patients were diagnosed according to the fulfillment of the Histiocytosis Society criteria proposed in 1991 and updated in 2004. The HScore includes 9 clinical, laboratory and histopathological criteria, and the score may range from 0 to a maximum of 337 points. Results By January 2015, the REGHEM registry included 111 adult patients with HS, 65 (59%) men and 46 (41%) women, with a mean age at diagnosis of 49.16 years (range 12-85 years); nineteen patients (17%) were not born in Spain (58% from Latin America, 21% from Africa and 16% from Asia). Tissular hemophagocytosis was confirmed in 97/107 (87%) cases. The main underlying diseases diagnosed before HS were autoimmune/rheumatological diseases in 36 (33%) patients, chronic infections in 24 (22%) and neoplasia in 25 (23%) patients. The great majority of patients required ICU admission and death occurred in 59 (53%). The HScore was retrospectively calculated in 61 patients in whom all the criteria required could be applied: the mean HScore was 230,03 (range, 58-306). No significant differences for the mean HScore were found with respect to gender, age at diagnosis, underlying diseases, or severe internal organ involvement (pulmonary, renal or central nervous system). However, a higher mean HScore was found in foreign patients (257 vs 222, p=0.02), in patients with concomitant infections with confirmed microbiological isolation (243 vs 214, p=0.022) and in those who required vital support (248 vs 212, p=0.004). Patients who died showed a higher mean HScore in comparison with survivors (241 vs 217, p=0.05). Conclusions Hemophagocytic syndrome is a life-threatening multisystemic disease that often requires vital support in intensive care units. Despite this and the use of a complex therapeutic approach, half of the patients died. We found higher HScores in patients presenting with a complicated HS (concomitant infections, need for vital support and death). The use of the new HScore as prognostic factor may help to identify patients with a poor outcome. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):404.2-404. DOI:10.1136/annrheumdis-2015-eular.4821 · 10.38 Impact Factor
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    ABSTRACT: To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of systemic activity measured by ESSDAI score. By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins [IVIG] and/or rituximab [RTX]). There were 1048 (94%) females and 72 (6%) males, with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255-23%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34-0.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents, patients as inadequately treated, mainly associated with articular involvement of low/moderate activity. The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted. Copyright © 2015 Elsevier B.V. All rights reserved.
    International immunopharmacology 04/2015; 74(Suppl 2). DOI:10.1016/j.intimp.2015.03.027 · 2.47 Impact Factor
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    ABSTRACT: Systemic autoimmune diseases (SAD) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1,000 patients) of SAD reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SAD. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodefficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SAD with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SAD to emerge. Copyright © 2015 Elsevier B.V. All rights reserved.
    Autoimmunity reviews 04/2015; 14(8). DOI:10.1016/j.autrev.2015.03.008 · 7.93 Impact Factor

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8k Citations
1,517.10 Total Impact Points


  • 2010-2015
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 1999-2015
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 1998-2015
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 1998-2014
    • Hospital Clínic de Barcelona
      • Servicio de Enfermedades Autoinmunes y Sistémicas
      Barcino, Catalonia, Spain
  • 2011
    • Hospital do Meixoeiro
      Vigo, Galicia, Spain
  • 2009
    • Hospital Son Dureta
      Palma, Balearic Islands, Spain
  • 2006
    • Hospital Clínico, Maracaibo
      Maracaibo, Zulia, Venezuela
  • 2002
    • Meritorious Autonomous University of Puebla
      Ejido Puebla, Baja California, Mexico
    • Hospital Egas Moniz
      Lisboa, Lisbon, Portugal
  • 2001
    • University of Cape Town
      • Department of Medicine
      Cape Town, Province of the Western Cape, South Africa