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Objective To evaluate the efficacy and safety of belimumab in patients with Primary Sjogren's syndrome (pSS). Methods The search included manuscripts assessing the efficacy or safety of belimumab in patients with pSS (American-European Consensus Criteria 2002) published between 2004 and 2017 in MEDLINE, EMBASE or Cochrane databases. Two reviewers independently selected the articles, extracted data and evaluated the quality of the evidence following Scottish Intercollegiate Guidelines Network (SIGN) recommendation grades. Results Out of 135 citations, only 3 articles were included. All of them publishing results from the same study at different time points including 28 patients. At week 28 improvement was reported for visual analogue scale (VAS) dryness score and glandular manifestations in 37% and 77% of patients, respectively, which persisted at week 52 (W52). Belimumab was well tolerated and safely administered. Conclusion Published evidence to determine the efficacy of belimumab in pSS is limited. Belimumab seems to be effective to reduce systemic activity, parotid enlargement, lymphadenopathies, articular manifestation and B cell biomarkers.

Objective The aim of this study is to describe the findings of a protocolised odontological evaluation of patients with primary Sjogren’s syndrome (pSS) treated in rheumatology units in the Community of Madrid. Methods Multicentric descriptive study in which pSS patients classified according to the American-European consensus of 2002 criteria were included. We collected the demographic, clinical and serological data of each patient. A complete oral examination was performed and salivary flow and the CAOD caries index were collected. The patients completed the visual analogue scale for xerostomia, the Oral Health Impact Profile-14 questionnaire and an oral health questionnaire. Results Sixty-one patients were recruited. Ninety-eight percent were women and the mean age of the patients was 57 years. Pathological oral signs (unstimulated salivary flow/salivary glands sialography/scintigraphy) were present in 52.5% of the patients, anti-Ro/anti-La were positive in 90.2%. Ninety-two percent of the patients reported xerostomia and 61% of the patients suffered from hyposialia. Thirty-five patients presented oral mucosa lesions. CAOD index was 16.97 ± 7.93 and visual analogue scale for xerostomia was 46.69 ± 14.43. The results of the OHIP-14 questionnaire were 23.13 ± 14.16. Patients with pathological oral signs obtained a significantly higher Oral Health Impact Profile-14 score (P = .03). We also found that patients with peripheral nervous system involvement obtained a significantly higher Oral Health Impact Profile-14 score (P = .001). Conclusions The presence of xerostomia in this cohort of pSS patients was high and hyposialia was present in 61% of the patients. Oral lesions appeared in more than half of the subjects. Oral health had a negative impact on the quality of life of patients with pSS, being higher in those with pathological objective oral signs and in those with peripheral nervous system involvement.

espanolObjetivo El objetivo de este estudio es describir los hallazgos de una evaluacion odontologica protocolizada en pacientes con sindrome de Sjogren primario (SSp) atendidos en las consultas de reumatologia de la Comunidad de Madrid. Metodos Estudio descriptivo multicentrico en el que se incluyeron pacientes con SSp clasificados segun criterios del consenso Europeo-Americano de 2002. Se recogieron datos demograficos, clinicos y serologicos. Se realizo una exploracion oral, se recogio el flujo salival y el indice de caries CAOD. Los pacientes rellenaron la escala visual analogica para xerostomia, el cuestionario Oral Health Impact Profile-14 y un cuestionario de salud oral. Resultados Se reclutaron 61 pacientes. El 98% fueron mujeres y la edad media fue de 57 anos. El 52,5% presentaban signos orales patologicos (flujo salival no estimulado/sialografia/gammagrafia de glandulas salivales) y el 90,2% antiRo/antiLa+. El 92% de los pacientes referian xerostomia y un 61% hiposialia. Treinta y cinco pacientes presentaron lesiones de la mucosa oral. El indice CAOD fue de 16,97 ± 7,93 y la escala visual analogica para la xerostomia fue de 46,69 ± 14,43. Los resultados del Oral Health Impact Profile-14 fueron de 23,13 ± 14,16. Los pacientes con signos orales patologicos obtuvieron una puntuacion en el Oral Health Impact Profile-14 significativamente mayor (p = 0,03), al igual que los pacientes con afectacion del sistema nervioso periferico (p = 0,001). Conclusiones La prevalencia de xerostomia en esta cohorte de pacientes con SSp fue muy elevada y el 61% de los enfermos presentaron hiposialia. Mas de la mitad de los pacientes sufrieron lesiones orales. La salud oral presento un impacto negativo en la calidad de vida de los pacientes con SSp, siendo mayor en aquellos pacientes con signos orales objetivos patologicos y en los que presentaban afectacion del sistema nervioso periferico. EnglishObjective The aim of this study is to describe the findings of a protocolised odontological evaluation of patients with primary Sjogren's syndrome (pSS) treated in rheumatology units in the Community of Madrid. Methods Multicentric descriptive study in which pSS patients classified according to the American-European consensus of 2002 criteria were included. We collected the demographic, clinical and serological data of each patient. A complete oral examination was performed and salivary flow and the CAOD caries index were collected. The patients completed the visual analogue scale for xerostomia, the Oral Health Impact Profile-14 questionnaire and an oral health questionnaire. Results Sixty-one patients were recruited. Ninety-eight percent were women and the mean age of the patients was 57 years. Pathological oral signs (unstimulated salivary flow/salivary glands sialography/scintigraphy) were present in 52.5% of the patients, anti-Ro/anti-La were positive in 90.2%. Ninety-two percent of the patients reported xerostomia and 61% of the patients suffered from hyposialia. Thirty-five patients presented oral mucosa lesions. CAOD index was 16.97 ± 7.93 and visual analogue scale for xerostomia was 46.69 ± 14.43. The results of the OHIP-14 questionnaire were 23.13 ± 14.16. Patients with pathological oral signs obtained a significantly higher Oral Health Impact Profile-14 score (P = .03). We also found that patients with peripheral nervous system involvement obtained a significantly higher Oral Health Impact Profile-14 score (P = .001) Conclusions The presence of xerostomia in this cohort of pSS patients was high and hyposialia was present in 61% of the patients. Oral lesions appeared in more than half of the subjects. Oral health had a negative impact on the quality of life of patients with pSS, being higher in those with pathological objective oral signs and in those with peripheral nervous system involvement.

Background Primary Sjogren's syndrome (pSS) is an autoimmune disease that leads to salivary and lacrimal gland dysfunction. The adaptive immune response associated with T helper-2 lymphocytes appears to be altered in these patients. Therefore, the objective of this study was to determine the salivary levels of interleukin (IL)-6, IL-5, and IL-4 in patients with pSS when compared to a healthy control (HC) group. The secondary objectives were to study whether ILs levels in pSS patients were associated with salivary flow, patient-reported outcomes (PROMs) for xerostomia and oral health quality of life (Oral Health Impact Profile-14 [OHIP-14]), pSS classification criteria and presence of extraglandular manifestations. Methods A case-control study was conducted in 36 patients with pSS and 35 HCs. Cytokine levels were measured using high-sensitivity multiplex map human immunoassays. Unstimulated and stimulated whole saliva were collected and patients filled out questionnaires. The Mann-Whitney U test, chi-squared test, and Spearman correlation test were used. Results Interleukin-6 was significantly higher in pSS patients than in HCs (P = .0001). IL-6 was significantly higher in pSS patients with a positive salivary gland biopsy (P = .04), whole stimulated saliva hyposalivation (P = .02), and presence of musculoskeletal disorders (P = .03). There was a non-significant positive correlation between IL-6 levels and PROMs for xerostomia (r = .31; P = .06) and OHIP-14 (r = .07; P = .68) in pSS patients. Levels of IL-4 and IL-5 were not detected in both pSS and HCs patients. Conclusions Salivary IL-6 levels are significantly associated with pSS patients, and therefore, it is hypothesized that this biomarker may be useful in the diagnosis and follow-up of this disease.

Background Candidiasis is the most frequent mycotic infection of the oral cavity. The aim of this study was to investigate the presence of clinical oral candidiasis and Candida albicans yeast in a population diagnosed of primary Sjögren’s syndrome (pSS) and to study the possible factors associated with this infection. Material and Methods An observational cross-sectional study was conducted in 61 pSS patients (60 women, 1 man, mean age 57.64±13.52) where patient based information (demographic and medical, tobacco and alcohol consumption history), intraoral parameters (presence of dentures, clinical signs of candidiasis), salivary analytical information (number of Candida albicans as colony-forming units per millilitre (CFU/mL), salivary pH levels, unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. Results 13.1% of pSS patients presented oral signs of candidiasis. Denture stomatitis and angular cheilitis were the most common lesions. 87.5% of patients with clinical candidiasis presented reduced pH levels and salivary flow in both UWS and SWS. A significant statistical negative correlation was found between CFU/mL of Candida albicans and levels of UWS and SWS. A negative correlation was found between pH levels and CFU/mL, although not statistically significant. Conclusions A reduced salivary flow may predispose pSS patients to Candida albicans overgrowth, which may show with clinical signs. Preventive measures are of great importance to avoid and to treat this condition promptly. Key words:Sjögren’s syndrome, oral candidiasis, oral lesions, Candida albicans, oral yeast, salivary flow rate, hyposalivation.

Introduction: Dynamical systems theory, probability, and entropy were the substrate for the development of the diagnostic and predictive methodology of adult heart dynamics. Objective: To apply a previously developed methodology from dynamical systems, probability, and entropy in both normal and pathological subjects. Methods: Electrocardiographic records were selected from 30 healthy subjects and 200 with different pathologies, with a length of least 18 h. Numerical attractors from dynamical attractors and the probability of occurrence of ordered pairs of consecutive heart rates were built. A calculation of entropy and its proportions was performed and statistical analysis was conducted. Results: The normal patients’ heart dynamics were evaluated according to the methodology of entropy proportions, highlighting that there are differences in normal patients with different pathologies. There was maximal level of sensitivity, specificity, and diagnostic agreement. Conclusion: Proportional entropy constitutes a diagnostic and predictive method of heart systems, and may be useful as a tool to objectively diagnose and perform the follow-up of normal and pathological cases.

Background and objectives Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. Material and methods Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014–2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. Results 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p

Resumen Objetivo Elaborar recomendaciones SER sobre el uso de agentes biologicos en el sindrome de Sjogren primario (SSp). Metodos Se identificaron preguntas clinicas de investigacion relevantes sobre el uso de agentes biologicos en el SSp. Las preguntas clinicas se reformularon en 4 preguntas PICO. Se diseno una estrategia de busqueda y se realizo una revision de la evidencia cientifica de estudios publicados hasta mayo de 2017. Se reviso sistematicamente la evidencia cientifica disponible. Se evaluo el nivel global de la evidencia cientifica utilizando los niveles de evidencia del SIGN. Tras ello, se formularon recomendaciones especificas. Resultados Se recomienda rituximab como el farmaco biologico de eleccion para las manifestaciones extraglandulares refractarias al tratamiento convencional. Se desaconseja el uso de agentes anti-TNF. La evidencia cientifica es escasa con belimumab y abatacept, por lo que deberian considerarse solamente en los casos resistentes a rituximab. Conclusiones El rituximab es el farmaco biologico de eleccion en las manifestaciones graves extraglandulares del SSp. Belimumab o abatacept podrian ser de utilidad en casos seleccionados.

OBJECTIVES To assess the effects of Xerostom® toothpaste and mouthwash in primary Sjogren's syndrome (pSS) patients with xerostomia. SUBJECTS AND METHODS A double-blinded, randomized study where patients were assigned at baseline test or control products. Patients used the products 3 times/day/28 days. We used a visual analogue scale (VAS) for xerostomia and an Oral Health Impact Profile-14 (OHIP-14), baseline and after treatment, to assess possible improvement. RESULTS A total of 28 patients with pSS were included in this study, but only 24 finished it (all women, mean age 55.21 ± 11.87), and 13 patients received the test and 11 the control. VAS and OHIP-14 scores decreased in both groups after treatment but significant differences between groups were not found. We do not detect VAS intragroup significant differences before and after treatment in test and control groups. A significant improvement in OHIP-14 was identified in the treatment group, while no significant differences were observed in the control group. No adverse effects were present. CONCLUSIONS Xerostom® toothpaste and mouthrinse may alleviate and improve quality of life without associated side effects, but further research with a larger number of participants and follow-up are necessary to establish the positive efficacy of these topical products in pSS patients.

Objectives To investigate the prevalence, associated factors, and effects of primary renal disease on morbidity in patients with primary Sjögren’s syndrome (pSS).Methods All patients in the SJÖGRENSER (registry of adult SSp patients of the Spanish Society of Rheumatology) cohort were retrospectively investigated for the presence of clinically significant renal involvement directly related to pSS activity.Results Of the 437 patients investigated, 39 (9%) presented overt renal involvement during follow-up. Severe renal disease necessitating kidney biopsy was relatively rare (23%). Renal involvement may complicate pSS at any time during the disease course and is associated with severe disease (indicated by higher scores of involvement, activity, and damage), systemic multiorgan involvement, and a higher frequency of lymphoma. Multivariate analysis showed that older age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.07), higher European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index scores (OR 1.1, CI 1.03–1.18), serum anti-La/SSB positivity (OR 6.65, CI 1.41–31.372), and non-vasculitic cutaneous involvement (OR 5.47, 1.03–29.02) were independently associated with this complication. Chronic renal failure developed in 23 of 39 patients (59%); only 1 of them progressed to end-stage renal disease necessitating renal replacement therapy. Patients with renal disease showed higher Sjögren’s syndrome disease damage index scores, higher rates of hospitalization due to disease activity and higher rates of clinically relevant comorbidities.Conclusion Renal involvement is an uncommon complication in pSS that was observed in 9% of patients. Although categorized as a non-negligible comorbidity, this condition shows a favorable prognosis.

Background To evaluate the presence of oral lesions in a group of patients with primary Sjögren’s syndrome (pSS) and compare these results with a matched control group (CG). Material and Methods An observational cross-sectional study was conducted. 61 pSS patients (60 women, 1 man, mean age 57.64±13.52) diagnosed according to the American European Criteria (2002), and 122 matched control patients (120 women, 2 men, mean age 60.02±13.13) were included. Demographic and medical data, oral lesions and salivary flow rate were collected. Results Compared with the controls, pSS patients were 3.95 more likely to have oral lesions (OR 3.95; 95% CI 2.06-7.58; p=0.0001). 57.4% pSS patients presented oral lesions compared to 25.4% in CG. The most common were candidiasis (13.1% vs 2.5%), traumatic lesions (13.1% vs 4.1%), apthae (8.2% vs 0), and fissuration of the tongue (8.2% vs 0.8%). pSS patients with oral lesions had lower salivary flow levels (stimulated and unstimulated), although these differences were not significant. Significant associations were found between the presence of oral lesions and systemic manifestations and history of parotid gland enlargement in pSS patients. Conclusions pSS patients suffer more oral lesions than general population and these lesions may aggravate the pSS disease. Key words:Sjögren’s syndrome, oral lesions, oral diseases, oral manifestations, oral disorders.

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age 64 years group, OR was 20.610 (4.679-90.774, p 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age 64 years, OR was 7.674 (1.675-35,151, p 0.009); disease duration, OR 1.049 (CI 1.003-1097, p 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.

To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination. Key points: • Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered. • However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required. • This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.

Background Primary Sjogren’s syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands. These patients have a higher risk than the general population of developing non-Hodgkin lymphoma (NHL). This risk also increases with the time of evolution of the disease. pSS is also associated with the development of non-hematological cancer such as thyroid, digestive or gynecological among others. Objectives The aim of the study is to explore the association between the development of neoplasia and demographic, clinical or therapeutic factors in pSS. Methods The SJOGRENSER registry is a multicenter, cross-sectional study of patients with pSS who meet the American-European consensus criteria of 2002, of 33 Spanish rheumatology units. The demographic, clinical, analytical, therapeutic and neoplastic data were collected through review of the clinical records and interviews with the patients. Previously, all the patients signed informed consent and the approval of the local ethic committees was obtained. Descriptive statistics was used for the analysis of the data. The chi-squared test was used to establish the statistical associations and it was considered a p Results Four hundred and thirty-seven patients were included in SJOGREN-SER Registry (female gender 95.19%; median age 58.3 years). We found 30 patients (6.86%) with neoplasia (3 of them with more than one neoplasia): 7 with lymphomas (23.3%) (4 MALT lymphomas, 2 Hodgkin’s lymphomas, 1 immunocytoma), 9 with gynecological neoplasia (30%), 2 with digestive malignancies, 2 with hematological, 2 with endocrine, 6 with malignancies in other locations, 3 with multiple mieloma and 2 patients with Waldenstrom macroglobulinemia. The results of the bivariate analysis are shown in the table. The factors significantly associated with the development of neoplasia were older age, glandular inflammatory involvement, lung involvement and use of rituximab. The age at diagnosis of the disease tended to be higher in the group with neoplasia (50.1 (± 12.9) vs 54.7 (± 11.7), p = 0.059). In the multivariate analysis, positive associations were found for the development of neoplasia in older patients (OR 1.045; CI95% 1.010-1.081), patients with glandular inflammation (OR 3.104; CI95% 1.396-6.906), and use of rituximab (OR 3.745; CI95% 1.386-10.118). Conclusion Thirty (6.86%) patients with pSS from the SJOGRENSER registry developed some neoplasia; the most frequent was gynecological, followed by lymphoproliferative processes. Older age, glandular inflammatory involvement and use of rituximab (presumably indication bias) were associated with the presence of neoplasia. References [1] Brito –Zeron, et al. Characterization and risk estimate of cancer in patients with primary Sjogren syndrome. Journal of hematology & oncology 2017;10:90. [2] Liang Y, et al. Primary Sjogren syndrome and malignance risk: a systematic review and meta-analysis. Ann Rheum Dis 2014;73:1151 Disclosure of Interests Monica Fernandez Castro: None declared, Carlos Sanchez-Piedra: None declared, Jose Luis Andreu: None declared, Jose Rosas Consultant for: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, UCB Pharma, Speakers bureau: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, UCB Pharma, Victor Martinez Taboada: None declared, Alejandro Olive: None declared

Background Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. Among the extraglandular manifestations, digestive involvement (DI) is frequent, and may condition the quality of life of these patients. There are few studies that systematically analyze gastrointestinal involvement in pSS. Objectives To describe the prevalence of DI in patients with pSS included in SJOGRENSER Spanish registry and the phenotype of these patients, and to analyze their association with other clinical manifestations, serological markers, activity index and treatments used. Methods Transversal multicenter study that includes all patients of SJOGRENSER registry (patients who meet 2002 pSS classification criteria), a study conducted in 33 units of rheumatology in Spain between 2014-2016, which collected demographic and clinical and serological data (1). Patients were classified according to the presence of DI (that included esophagus, stomach, intestine, liver and pancreas). A descriptive analysis was done, with means and standard deviations, frequencies and proportions. Student t for quantitative variables and Chi2 for qualitative ones were performed to evaluate differences between groups. The association of DI with other variables was analyzed by bivariate and multivariate binomial logistic regression analysis. In the multivariate model all variables with p Results From 437 patients included (95% women, median age of 58 years), 59 (13.5%) had some DI (21 (36%) chronic atrophic gastritis, 12 (20%) esophageal dismotility, 3 (5%) lymphocytic colitis, 23 (39%) other). 54% of patients developed DI at the time of pSS diagnosis or later, and 45% before the diagnosis, with a mean age of 49 years at the onset of pSS symptoms. Patients with DI were older, both at diagnosis, onset of pSS symptoms and inclusion in the cohort, than those without it. There were no differences in the ESSDAI index between both groups. Comparison regarding clinical and serological characteristics is shown in Table 1. Patients with DI had more thyroid involvement and C3 hypocomplementemia. In addition, patients with DI had been treated more frequently with glucocorticoids and immunosuppressants. In the multivariate analysis, DI was significantly associated with older age at diagnosis (OR 1.03 (1.00-1.05); p=.005), more C3 hypocomplementemia (OR 2.40 (1.10-5.26) p=.027) and absence of anti-Ro antibodies (OR 0.33 (0.12-0.87) p=.025). Conclusion In patients with pSS from the SJOGRENSER cohort, the prevalence of digestive involvement is 13.5%. These patients are older at diagnosis, have more C3 hypocomplementemia and negative anti-Ro antibodies. These patients need more frequently glucocorticoids and immunosuppressants, suggesting a more severe disease phenotype. Reference [1] Fernandez Castro M, Reum Clin2016; 12:184-9 Disclosure of Interests Sheila Melchor: None declared, Carlos Sanchez-Piedra: None declared, Monica Fernandez Castro: None declared, Jose Luis Andreu: None declared, Victor Martinez Taboada: None declared, Alejandro Olive: None declared, Jose Rosas Consultant for: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, UCB Pharma, Speakers bureau: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, UCB Pharma, Patricia Carreira: None declared

Background Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease characterized by the involvement of the exocrine glands, mainly salivary and lacrimal glands. Approximately half of patients will experience extraglandular complications throughout their evolution. Objectives To characterize the involvement of the nervous system (NS) in patients with pSS. Methods Multicenter cross-sectional study of a cohort of patients with pSS, constructed by random selection of pSS patients fulfilling the 2002 American-European Consensus Criteria for pSS1 from 33 rheumatology units. Through review of clinical records and interview with patients, demographic, clinical, analytical, therapeutic data and disease activity indexes were collected. Univariate analysis was done by Chi square test, Mann-Whitney U test and Student’s t test. Multivariate analysis was done by linear logistic regression. A p Results 437 patients were included (95% women, median age of 58 years). 65 patients developed NS involvement: 26 patients central NS, 31 peripheral NS and 8 both. Multivariate analysis showed association between NS involvement and atherosclerotic stroke (OR 10.4, 95% CI 2.8-38.5), ear disease (OR 2.1, 95% CI 1.1-4.2) and myopathy (OR 6.5, 95% CI 1.3-31,6). Patients with NS involvement had higher probability of being treated with glucocorticoids (OR 3.3, 95%CI 1.5-7.2) and cyclophosphamide (OR 6.8, 95% CI 1.5-31). Conclusion 15% of patients with pSS develope NS involvement that is associated with atherosclerotic stroke, ear disease and myopathy. Reference [1] Vitali C. et al. Ann Rheum Dis 2002; 61:554 Disclosure of Interests Jose Luis Andreu: None declared, Carlos Sanchez-Piedra: None declared, Monica Fernandez Castro: None declared, Victor Martinez Taboada: None declared, Alejandro Olive: None declared, Jose Rosas Consultant for: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, UCB Pharma, Speakers bureau: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, UCB Pharma, Raul Menor-Almagro: None declared, Beatriz Rodriguez Lozano: None declared, Angel Garcia-Aparicio: None declared, Francisco J Lopez-Longo: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Jesus ALberto Garcia Vadillo: None declared, Susana Gil: None declared, Ruth Lopez Gonzalez: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Carles Galisteo: None declared, Jorge Juan Gonzalez Martin: None declared, M E Ruiz: None declared, Inigo Rua-Figueroa: None declared, Oscar Illera: None declared, Lurdes Romani: None declared, Sheila Melchor: None declared, Begona Moreira: None declared, Enrique Raya: None declared, Jose M Pego-Reigosa: None declared, Natalia Cid Boza: None declared, Enrique Judez: None declared, Clara Moriano: None declared, Vicente Torrente: None declared, Hector Corominas: None declared, Blanca Garcia-Magallon: None declared, Carlos Guillen-Astete: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Cristina Bohorquez: None declared, Javier Loricera: None declared, Joaquin Belzunegui: None declared

Background: Belimumab is a human IgG1l monoclonal antibody directed against BAFF, a B lymphocyte survival factor. It is indicated as adjuvant treatment in adult patients with active systemic lupus erythematosus (SLE), with positive autoantibodies and with a high degree of activity of the disease despite standard treatment. Objectives: This study aims to describe a sample of patients diagnosed with SLE who received treatment with belimumab in a tertiary hospital. Methods: Retrospective longitudinal unicentric observational study. Clinical records of all patients diagnosed with SLE who had received treatment with belimumab were reviewed. Demographic characteristics, clinical manifestations and reason for belimumab indicaton were collected. Results: The twelve patients included in the sample were women. Median age was 48.5 years (31-70). The most frequent reason for indication of belimumab was uncontrolled arthritis. The average time of treatment with belimumab in the total sample was 27.5 (+/- 26.24) months, with a median of 12 months (4-78). Mean treatment time (cases in which belimumab was discontinued excluded) was 31.25 (+/- 26.98) months with a median of 25 (5-78). The average dose reduction of prednisone after initiation of treatment with belimumab (in patients in which it was considered effective) was 5 mg per day (+/- 5). It should be noted that of the 14 cases, treatment was only discontinued in 4 patients, 2 of which were withdrawn due to ineffectiveness. There were 2 adverse events that required drug withdrawal: neutropenia and urothelial carcinoma. (Table). Conclusion: BLM is a well tolerated drug and effective in clinical practice. Adverse effects leading to drug withdrawal are infrequent. Disclosure of Interests: Carolina Merino Argumanez: None declared, Olga Rusinovich: None declared, Consuelo Ramos Giraldez Speakers bureau: Sanofi, Maria Espinosa: None declared, Hilda Godoy: None declared, Carmen Barbadillo Mateos: None declared, Jose Campos Esteban: None declared, Mercedes Jimenez Palop: None declared, Jesus Sanz: None declared, Luis Fernando Villa Alcazar: None declared, Carlos Isasi Zaragoza : None declared, Monica Fernandez Castro: None declared, Jose Luis Andreu Sanchez: None declared

Objective: To compare the prevalence of the main comorbidities in two large cohorts of patients with Primary Sjogren's Syndrome (pSS) and Systemic Lupus Erythematosus (SLE), with focus on cardiovascular (CV) diseases. Methods: Cross-sectional multicenter study where the prevalence of more relevant comorbidities in two cohorts was compared. Patients under follow-up from the SJOGRENSER (Spanish Rheumatology Society Register of pSS) and RELESSER (Spanish Rheumatology Society Register of SLE) registries, and who fulfilled the 2002-AECG and 1997-ACR classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when it was judged appropriate. Results: A total of 437 pSS patients (95% female) and 2,926 SLE patients (89% female) were included. Mean age: 58.6 (p55-p75: 50.0-69.9) and 45.1 years (36.4-56.3), respectively (p

Resumen Objetivo Describir los objetivos y metodologia del registro de sindrome de Sjogren primario (SSp) de la Sociedad Espanola de Reumatologia (SJOGREN-SER). Metodos Estudio transversal descriptivo multicentrico de pacientes con SSp que cumplen los criterios de clasificacion del consenso europeo-americano del 2002 atendidos en servicios de reumatologia espanoles. Cohorte elaborada a partir de la seleccion al azar de pacientes con SSp. Los datos se obtuvieron de la historia clinica y por entrevista medica al paciente el dia de la inclusion en el estudio. Se recogieron 298 variables agrupadas en caracteristicas epidemiologicas, clinicas, serologicas y terapeuticas, asi como diferentes desenlaces reportados por el paciente. El estudio fue aprobado por los CEIC locales y los pacientes firmaron un consentimiento informado. Para el analisis de los datos se utilizo estadistica descriptiva, se analizaron medias, medianas y frecuencias, con sus respectivas desviaciones y rangos intercuartilicos de las variables recogidas (p25-p75). Resultados Han participado 33 centros espanoles. El numero de pacientes incluidos es de 437, la mayoria mujeres (95%), con una mediana de edad al diagnostico de SSp de 50 anos. La mediana de edad de esta cohorte es de 58 anos. La mayoria de los pacientes (95%) presenta sindrome seco y hasta el 94% anti-Ro positivo. Un total de 119 pacientes (27%) cumplen los nuevos criterios de clasificacion SICCA-ACR de 2012. Conclusiones SJOGREN-SER ha sido disenado con el fin de caracterizar una cohorte representativa de pacientes con SSp en nuestro pais, en situacion de practica clinica habitual, para analizar la magnitud y distribucion de sus manifestaciones, la actividad, el dano acumulado y el manejo terapeutico de la enfermedad. Esto nos permitira ampliar y actualizar el conocimiento sobre esta enfermedad y planificar estrategias de actuacion en el SSp.

Objective To describe the objectives and methods of the Spanish Society of Rheumatology primary Sjogren syndrome (pSS) registry (SJOGREN-SER). Methods This is a multicenter descriptive transversal study of a cohort of pSS patients fulfilling European/American consensus criteria collected from Rheumatology clinics all over Spain. Patients were included by randomisation from an anonymised list provided by every department. Data were collected by reviewing clinical records and an interviewing the patients. Two hundred and ninety eight variables were investigated: epidemiological, clinical, serological characteristics, treatments and complications. Informed consent was obtained and local ethics committees approved the study. Variables were analyzed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25–p75). Results A total of 3 rheumatology departments participated in the registry. A total of 437 patients were included. And 95% of them were women, with a median age of 58. Median age at pSS's diagnosis was 50 years. Dryness symptoms (95%) were the most frequent complaint and anti-Ro/SS-A were present in 94% of the cases. Only 27% of the patients fulfilled the new 2012 SICCA-ACR classification criteria. Conclusions SJOGREN-SER has been designed in order to characterize a representative pSS Spanish cohort, in clinical daily practice, to analyze the magnitude and distribution of its manifestations, activity, accumulated damage and therapeutic management of the disease. This will allow broadening the knowledge of this disease and plan strategies of action in pSS.

To assess the effects of XerostomA double-blinded, randomized study where patients were assigned at baseline test or control products. Patients used the products 3 times/day/28 days. We used a visual analogue scale (VAS) for xerostomia and an Oral Health Impact Profile-14 (OHIP-14), baseline and after treatment, to assess possible improvement.A total of 28 patients with pSS were included in this study, but only 24 finished it (all women, mean age 55.21 ± 11.87), and 13 patients received the test and 11 the control. VAS and OHIP-14 scores decreased in both groups after treatment but significant differences between groups were not found. We do not detect VAS intragroup significant differences before and after treatment in test and control groups. A significant improvement in OHIP-14 was identified in the treatment group, while no significant differences were observed in the control group. No adverse effects were present.Xerostom

To formulate SER recommendations for the use of biological agents in primary Sjögren's syndrome (pSS).Relevant clinical research questions were identified on the use of biological agents in pSS. The clinical questions were reformulated into 4PICO questions. A search strategy was designed and a review of the scientific evidence of studies published until May 2017 was carried out. The scientific evidence available was systematically reviewed. The overall level of scientific evidence was assessed using the SIGN evidence levels. After that, specific recommendations were made.Rituximab is recommended as the biological agent of choice for extraglandular manifestations refractory to conventional treatment. The use of anti-TNF agents is discouraged. The scientific evidence with belimumab and abatacept is scarce, so they should be considered only in cases refractory to rituximab.Rituximab is the biological agent of choice in severe extraglandular manifestations of pSS. Belimumab or abatacept may be useful in selected cases.

The aim of this study is to describe the findings of a protocolised odontological evaluation of patients with primary Sjögren's syndrome (pSS) treated in rheumatology units in the Community of Madrid.Multicentric descriptive study in which pSS patients classified according to the American-European consensus of 2002 criteria were included. We collected the demographic, clinical and serological data of each patient. A complete oral examination was performed and salivary flow and the CAOD caries index were collected. The patients completed the visual analogue scale for xerostomia, the Oral Health Impact Profile-14 questionnaire and an oral health questionnaire.Sixty-one patients were recruited. Ninety-eight percent were women and the mean age of the patients was 57 years. Pathological oral signs (unstimulated salivary flow/salivary glands sialography/scintigraphy) were present in 52.5% of the patients, anti-Ro/anti-La were positive in 90.2%. Ninety-two percent of the patients reported xerostomia and 61% of the patients suffered from hyposialia. Thirty-five patients presented oral mucosa lesions. CAOD index was 16.97±7.93 and visual analogue scale for xerostomia was 46.69±14.43. The results of the OHIP-14 questionnaire were 23.13±14.16. Patients with pathological oral signs obtained a significantly higher Oral Health Impact Profile-14 score (P=.03). We also found that patients with peripheral nervous system involvement obtained a significantly higher Oral Health Impact Profile-14 score (P=.001) CONCLUSIONS: The presence of xerostomia in this cohort of pSS patients was high and hyposialia was present in 61% of the patients. Oral lesions appeared in more than half of the subjects. Oral health had a negative impact on the quality of life of patients with pSS, being higher in those with pathological objective oral signs and in those with peripheral nervous system involvement.

Background Belimumab is a human monoclonal antibody that inhibits B-cell activating factor shown to be efficacious in systemic lupus erythematosus. In other B cell mediated autoinmune disease such as primary Sjogren’s syndrome(pSS) the efficacy is unclear. Objectives To evaluate the efficacy of belimumab in patients with pSS. Methods A systematic literature review was perfomed (EMBASE, MEDLINE and Cochrane) as part of the Spanish Rheumatology Society’s Recommendations for the Use of Biological Therapies in Primary Sjogren’s Syndrome. Inclusion criteria was defined as: Population: patients with pSS according to American-European Consensus Criteria 2002 Intervention: belimumab; Control: synthetic or biologic DMARDs, corticosteroids, ursodesoxicolic acid or placebo; Outcome: efficacy in dryness, glandular and extraglandular manifestations. Studies with Results 3 articles were included out of 135. All of them published results from the same study1 at different timepoints. The study design was experimental but with a small sample size and no control group or randomization. The article of Mariette et al 20151 evaluated the efficacy and safety of belimumab in 30 patients with systemic activity or early disease until week 28(W28). There was a significant decrease in mean ESSDAI (8.8 to 6.3 p=0.02), ESSPRI (6.4 to 5.6 p=0.02) and VAS for dryness (7.8 to 6.2 p=0.02). Physician’s VAS for disease systemic activity also decreased in 43% as well as parotid inflammation in 76.9% of patients. Also, B cell biomarkers decreased: IgG (21.2 to 18.2 g/L, p=0.02), IgA (3.7 to 3.3 g/L, p=0.04), IgM (1.6 to 1.3 g/L, p The study of De Vita et al 20152 compared results at week 52 (W52) and W28 in 19 patients, of whom 15 had previously responded to treatment. Of these 15 patients 13 maintained response and 3 out of the 4 patients that did not respond achieved primary outcome. The improvement at W52 continued for ESSDAI, glandular inflammation, lympadenopathy and joints. B cell biomarkers remained stable. Overall items conributing to ESSDAI descreased but only physician’s VAS for disease systemic activity was statistically significant (3.2 W28 vs 2.5 W52; p=0.04). The study of Quartuccio et al.3 compared clinical and lab variables of W52 with 12 months of follow up after interrupting belimumab. A significant decrease in ESSDAI in 9 out of 13 patients (3.5±3.7 vs 7.0±5.7; p Conclusions Published evidence to determine the efficacy of belimumab in primary Sjogren is limited and poor. Belimumab seems to be effective to reduce systemic activity, parotid enlargement, dryness, lymphadenopathies, articular manifestation, fatigue and B cell biomarkers. References [1] ARD 2015;74:526–531. [2] Rheumatology2015;54(12):2249–56. [3] Clin Exp Rheumatol2016;34(2):311–4. Acknowledgements This Project has been financed by the SER. Disclosure of Interest None declared

Resumen El sindrome de Sjogren primario (SSp) es una enfermedad autoinmune sistemica cronica, que cursa con destruccion del tejido glandular lagrimal y salival. Sus sintomas mas frecuentes y tempranos son la sequedad oral y ocular. La sequedad oral dificulta que el paciente hable, deguste y mastique correctamente, lo que disminuye la calidad de vida del enfermo. Los signos y sintomas orales mas frecuentes son la hiposialia con o sin xerostomia, la caries dental, las infecciones fungicas, las lesiones orales traumaticas, la disfagia, la disgeusia y la inflamacion de las glandulas salivales. Existen distintas estrategias terapeuticas en funcion de la gravedad de cada caso que aumentan la cantidad de saliva y disminuyen el numero de caries e infecciones orales. Por ello, es de especial importancia establecer una relacion cercana entre el dentista y el reumatologo que permita hacer un diagnostico temprano y correcto, fomentar las medidas dieteticas e higienicas adecuadas, tratar y prevenir las posibles complicaciones orales.

Background Sjögren’s syndrome (SS) is an autoimmune disease related to two common symptoms: dry mouth and eyes. Although, xerostomia and hyposialia have been frequently reported in these patients, not many studies have evaluated other oral manifestations. The aim of this systematic review was to investigate prevalence rates of oral lesions (OL) in SS patients and to compare it to a control group (CG), when available. Material and Methods An exhaustive search of the published literature of the Pubmed, Scopus, Web of Science and the Cochrane Library databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) for relevant studies that met our eligibility criteria (up to September 1st 2017). Results Seventeen cross-sectional studies and one cohort study were finally included. The results showed that SS patients presented more OL compared to non-SS patients. The most frequent types of OL registered in primary and secondary SS were angular cheilitis, atrophic glossitis, recurrent oral ulcerations and grooves or fissurations of the tongue, also when compared to a CG. Conclusions OL are common and more frequent in SS patients when compared to a CG. This may be a consequence of low levels of saliva. More studies where these OL and all the possible cofounding factors are taken into account are needed. Key words:Sjögren’s syndrome, oral lesions, oral diseases, oral manifestations, oral disorders, systematic review.

To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources.

Primary Sjogren syndrome (PSS) is an autoimmune disease characterized by lymphocytic infiltration in exocrine glands, mainly the salivary and lachrymal glands, resulting in xerophthalmia and xerostomia. Occasionally, PSS has extra-glandular manifestations, including central (CNS) and peripheral nervous system (PNS) involvement. The reported prevalence varies in the literature, mainly because of heterogeneity in the diagnostic and classification criteria. Involvement of the PNS is more frequent than that of the CNS, presenting as axonal, sensory, autonomic or small fiber neuropathies and mononeuritis multiplex. CNS manifestations may be focal or diffuse and are associated with increased extra-glandular involvement and the presence of autoantibodies. Treatment is based on corticosteroids. In severe, refractory- or corticosteroid-dependant cases, immunosuppressant agents such as azathioprine or cyclophosphamide may be useful. Observational studies have suggested that rituximab is useful in some PSS extra-glandular manifestations. Currently, clinical trials with new biological agents such as belimumab and epratuzumab are being conducted in PSS.

To assess fibromyalgia (FM) prevalence in a large cohort of primary Sjögren's syndrome patients (pSS) from a National Database.Data included in the national retrospective register of pSS patients of the Spanish Society of Rheumatology (SJOGRENSER) were analysed.437 pSS patients were included and a 14.6% of FM prevalence was found. FM-pSS patients significantly showed more constitutional, fatigue and arthralgia symptoms, splenomegaly, genital, skin and ear involvement and dyslipidaemia (p0.05), as well as higher ESSPRI and SSDAI scores (p0.01). Several symptomatic treatments were more frequently used in FM-pSS patients. No differences were observed in laboratory markers, imaging techniques or histologic inflammatory findings. Patients with FM showed statistically more fatigue than pSS without FM. In the multivariate logistic regression analysis several features were associated to pSS-FM patients.We show data on a reliable prevalence of FM in pSS patients and its multiple associated factors along with the presence of higher disease activity scores than patients who did not show FM. The presence of fatigue, arthralgia, constitutional symptoms and dyslipidaemia were more likely to coexist in pSS-FM patients.

To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases.This was a cross-sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American-European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate.A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range [IQR] 50.0-69.9 years) for primary SS patients and 45.1 years (IQR 36.4-56.3 years) for SLE patients (P 0.001), and disease duration was 10.4 years (IQR 6.0-16.7 years) and 13.0 years (IQR 7.45-19.76 years), respectively (P 0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio [OR] 0.36 [95% confidence interval (95% CI) 0.28-0.48], 0.74 [95% CI 0.58-0.94], and 0.50 [95% CI 0.38-0.66], respectively) as were life-threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 [95% CI 0.35-0.92]). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 [95% CI 1.35-14.43]). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 [95% CI 0.39-0.76]; P 0.001).Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater.

BACKGROUND: Fungal arthritis is usually of haematogenous origin, and mainly affects patients with impaired cellular immunity or users of intravenous drugs. The infection in immunocompetent patients is generally caused by direct inoculation of the microorganism through an invasive device. The experience of azole therapy in these patients is limited. CASE REPORT: We report a case of arthritis caused by Scedosporium apiospermum characterized by its slow onset, lack of response to posaconazole and caspofungin, and its successful resolution after surgical debridement and treatment with voriconazole. CONCLUSIONS: Treatment with voriconazole and surgical debridement is an effective therapy for arthritis due to S. apiospermum.

Objective: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. Methods: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. Results: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0–8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. Conclusion: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

Systemic sclerosis (SSc) is a complex autoimmune disease which genetic component has not been yet completely understood. IL6 encodes a cytokine with a crucial role in the development of autoimmunity and fibrosis and its actions mainly are controlled by IL-6 receptor (IL-6R). We aimed to investigate whether the functional genetic variants rs8192284 and rs2228044 previously associated with several autoimmune diseases, located within the IL-6 receptor (IL-6R) subunits IL6R and IL6ST genes, respectively, are involved in the susceptibility to SSc and/or its major clinical subphenotypes. A Spanish cohort including 1013 SSc patients and 1375 controls was genotyped using the TaqMan® allelic discrimination technology. SSc patients were subdivided according to the major clinical forms, autoantibody status and presence of fibrotic lung affection. Our data showed no influence of the selected variants in global SSc susceptibility (rs8192284: P=0.67, odds ratios (OR)=0.98; rs2228044: P=0.99, OR=1.00). Similarly, the clinical/autoantibody subphenotype analyses did not yielded significant results. Our data suggest that the analyzed polymorphisms may not play a significant role in the SSc susceptibility.

A biomarker is a biological parameter that can be measured in blood or other body fluids or tissues and used as a sign of a normal or abnormal process, or of a condition or disease. In medicine, a biomarker can be used to diagnose a disease, to establish its prognosis or as a surrogate marker of outcome in research. In recent years, there has been strong interest in discovering new biomarkers, as well as in the development of new uses for well-known biomarkers in distinct diseases. In this article, the utility of several biomarkers not routinely used in rheumatology (procalcitonin, natriuretic peptides and cardiac troponins) in the diagnosis and follow-up of patients with systemic autoimmune diseases is reviewed.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Autoantibody production plays a critical role in its pathogenic pathways. Thus, B-cell directed biologic therapy is a logical option. The present article reviews the latest advances in the development of B-cell directed biological agents in the treatment of SLE. Rituximab has been studied in a number of open series of patients that suggest efficacy but two recent controlled clinical trials have failed to show efficacy versus placebo. In contrast, a recent placebo-controlled, double-blind, randomized trial has reported that belimumab has statistically significant efficacy versus placebo. Atacicept, a fusion protein that blocks cytokines that play a critical role in the differentiation and survival of B-cells and plasma cells, markedly reduces autoantibody levels but could increase the risk of infection. Further studies are needed to establish the role of B-cell directed biologic therapy in SLE.

No effective treatment has been documented for the glandular primary Sj ¨ ogren syndrome (PSS) despite the development of oral and biologic agents that have significant activity against other autoimmune disorders. Some disease-modifying agents have been empirically evaluated for the treatment of PSS. Targeting B cells also seems very promising in SSP because of the B-cell hyperactivity recognized in this desease. This article reviews existing data on the use of disease-modifying therapy for glandular of SSP. To date, published studies and trials of oral DMARDs for the treatment of SSP have shown disappointing results. B-cell modulation is clearly a promising therapy for PSS. Many challenges in trial design and execution are evident from the studies reviewed.

Shoulder pain is one of the most common presenting complaints in daily clinical practice. The assessment of patients with shoulder pain is usually complicated due to the wide variety of possible etiologies. Physical examination of the shoulder is especially important in the assessment of soft tissue disorders, since there are a number of physical examination manoeuvres specifically designed to examine particular structures. In this article, the various clinical tests and their diagnostic utility for examining subacromial impingement, supraspinatus, infraspinatus, subscapularis and biceps tendons, gleno-humeral instability and the acromioclavicular joint are reviewed and compared with procedures considered as the gold standard.

Objective Shoulder pain is a common complaint, frequently caused by subacromial impingement syndrome (SIS). There are a number of physical examination (PE) manoeuvres that explore the subacromial space. MRI provides an accurate anatomic image of the subacromial space, being the current gold standard in the diagnosis of SIS. The aim of this study is to evaluate the accuracy of the PE in the diagnosis of SIS and/or subacromial-subdeltoid bursitis (SSB) confirmed by MRI. Methods Consecutive outpatients with an episode of shoulder pain were prospectively included in the study. They were examined by a rheumatologist and, within 3 days, an MRI was done. Sensitivity, specificity, positive and negative predictive values, and accuracy of PE manoeuvres were calculated using a 2 x 2 table. Results Fourteen males and 16 females were included. All the tests exhibited acceptable sensitivity. As a result Yocum manoeuvre was considered the most sensitive and most accurate for SIS. With regard to SSB, the Gerber test was the most sensitive. The majority of the PE manoeuvres showed low specificity. Conclusions Most PE manoeuvres identify reasonably well subacromial impingement of the shoulder, although, in general, they have low specificity. The Yocum test has the best sensitivity and precision. Our data suggest that imaging techniques should be recommended to better define shoulder lesions.

Objectives. To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. Methods. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Results. Three damage clusters were identified. Cluster (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 10096 in clusters 2 and 3. P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 0.096 of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. Conclusion. In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

provide solid evidence that low-dose GC can inhibit radiographic damage in early RA, and that side effects of GC, when used in that clinical framework, are limited to hyperglycaemia, cataracts, and transient weight gain.

Objective The development of common variable immunodeficiency (CVID) or hypogammaglobulinemia in systemic lupus erythematosus (SLE) is rare. The purpose of this article is to provide a detailed review of lupus-associated CVID and to identify clinical characteristics and laboratory features in patients with SLE-associated CVID. Methods We describe 2 patients with SLE and CVID and review the cases published in the English literature highlighting both the demographic and the clinical characteristics and the laboratory and therapeutic aspects of this disorder. Results Detailed descriptions of 18 patients were available; 89% were females with a mean age at the onset of SLE of 23.8 years. In 50% of patients CVID developed within the first 5 years after the diagnosis of SLE. All patients had been treated with corticosteroids and 72% had also received immunosuppressive therapy. Sinopulmonary infections were the most frequent symptom. SLE disease activity decreased after the development of CVID in 67% of patients. Most patients (89%) were treated with gammaglobulin therapy. The most notable immunological feature was a reduced number or percentage of B-cells in 60% of patients. Conclusions CVID should be suspected in any SLE patient with recurrent sinopulmonary infections in the absence of SLE activity and/or immunosuppressive treatment.

Current treatment options for systemic lupus erythematosus (SLE) fail to control all the manifestations of the disease or fully prevent flares. The most extensively studied biological therapies are directed against B cells, although other biological targets have also been explored. Biological agents against tumor necrosis factor-alfa differ in their efficacy and have been associated with the generation of antinuclear and anti-dsDNA antibodies. Anti-interleukin-10 and anti-interleukin-6 agents have also been studied, with encouraging results. Abatacept, which has been approved in rheumatoid arthritis, has not shown efficacy in placebo-controlled clinical trials.

Primary Sjogren's syndrome is a chronic systemic autoimmune disease that causes destruction of lacrimal and salivary glands. The most common and earliest symptoms are oral and ocular dryness. Dry mouth makes talking difficult, tasting and chewing properly, impairing quality of life of these patients. The most common oral signs and symptoms are hyposialia with or without xerostomia, tooth decay, fungal infections, traumatic oral lesions, dysphagia, dysgeusia, and inflammation of salivary glands. There are different therapeutic strategies, depending on the severity of each case, and the increase in the amount of saliva, to reduce the number of cavities and oral infections. It is particularly important to establish a close relationship between the dentist and the rheumatologist in order to make an early and correct diagnosis, promoting appropriate dietary and hygiene measures, as well as to treat and prevent potential oral complications.

El tratamiento con agentes contra el factor de necrosis tumoral (TNF) alfa se ha asociado a la reactivacion de la infeccion cronica por el virus de la hepatitis B. Algunos casos publicados indican la necesidad de tratamiento cronico con lamivudina cuando se utilizan los agentes anti-TNFa. Describimos el caso de un paciente con espondilitis anquilosante y antigeno de superficie positivo tratado con infliximab y lamivudina. La respuesta clinica fue excelente, pero cuando el paciente interrumpio el tratamiento con lamivudina, se observo reactivacion de la replicacion viral. Una vez reinstaurado dicho tratamiento, se controlo nuevamente la replicacion viral y se normalizaron las concentraciones de transaminasas. Esta observacion indica que en pacientes con infeccion cronica por VHB que necesitan tratamiento anti-TNFa, se requiere un tratamiento preventivo a largo plazo con lamivudina.

Anti-tumor necrosis factor-a (TNF) therapy has been associated with reactivation of hepatitis B virus infection. Case reports have suggested the concomitant need of lamivudine treatment in patients with HBV infection treated with antiTNFa agents. We describe a case of ankylosing spondylitis with positive HBV surface antigen (HBsAg) treated with infliximab and lamivudine. Clinical response was excellent but when lamivudine therapy was stopped, reactivation of replication viral occurred. After the reintroduction of lamivudine, viral replication was controlled and liver function tests were normalized. Preventive long-term lamivudine therapy is mandatory when anti-TNFa therapy is maintained in patients with chronic HBV infection.