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To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS).All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies.We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases.We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Objectives Several IgG4-related disease (IgG4-RD) phenotypes have been proposed and the first set of classification criteria have been recently created. Our objectives were to assess the phenotype distribution and the performance of the classification criteria in Spanish patients as genetic and geographical differences may exist. Methods We performed a cross-sectional multicentre study (Registro Español de Enfermedad Relacionada con la IgG4, REERIGG4) with nine participating centres from Spain. Patients were recruited from November 2013 to December 2018. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) were used. Results We included 105 patients; 88% had Caucasian ethnicity. On diagnosis, 86% met the international pathology consensus while 92% met the Japanese comprehensive criteria. The phenotype distribution was head and neck 25%, Mikulicz and systemic (MS) 20%, pancreato-hepato-biliary (PHB) 13%, retroperitoneal and aorta (RA) 26%. Sixteen per cent had an undefined phenotype. Seventy-seven per cent of the cases met the AECC. From the 24 patients not meeting the AECC, 33% met exclusion criteria, and 67% did not get a score ≥20 points. Incomplete pathology reports were associated to failure to meet the AECC. Conclusions The PHB phenotype was rare among Spanish IgG4-RD patients. The MS phenotype was less frequent and the RA phenotype was more prevalent than in other, Asian patient series. An undefined phenotype should be considered as some patients do not fall into any of the categories. Three quarters of the cases met the 2019 AECC. Incomplete pathology reports were the leading causes of failure to meet the criteria.

Resume Contexte La maladie associee aux IgG4 (MAG-4) est une maladie auto-immune qui declenche une cascade inflammatoire aboutissant a une fibrose. Les criteres d’evaluation sont limites et les options therapeutiques insuffisamment explorees. Objectifs Evaluer la variation du score d’activite de la MAG-4 (IgG4-RI) dans une cohorte de patients atteints et explorer leurs traitements et resultats. Methodes Nous avons etudie le phenotype clinique, la gravite de la maladie et la reponse au traitement dans une etude longitudinale multicentrique ambispective menee dans 14 hopitaux en Espagne. Tous les patients remplissaient les criteres de diagnostic du consensus international de 2012 sur cette maladie. Resultats Soixante-huit patients ont ete inclus, d’âge moyen 53,4 ans, avec une predominance d’hommes. Les tissus les plus frequemment touches etaient le retroperitoine (33 %), des pseudotumeurs de l’orbite (28 %) et les sinus maxillaires et paranasaux (24 %). Le score IgG4-RI etait plus eleve lorsque plusieurs organes etaient atteints et avant traitement. Il diminuait apres le traitement, ce qui est conforme aux taux eleves de reponse au traitement. La plupart des patients ont ete traites par glucocorticoides (GC), chirurgie, azathioprine (AZA), mycophenolate mofetil (MMF) ou rituximab (RTX). La plupart des episodes d’activite de la MAG-4 ont ete pris en charge avec des GC seuls, des GC et une intervention chirurgicale ou des GC et de l’AZA. Les taux de reponse etaient eleves pour tous les traitements mais les rechutes et les poussees etaient frequentes. Conclusion Le score IgG4-RI, encore en developpement, est un indicateur prometteur dans la MAG-4. Les algorithmes de traitement ne sont pas clairement definis. Les GC et le RTX sont les traitements medicamenteux disponibles soutenus par le plus d’elements probants. Il est possible que les traitements de fond antirhumatismaux jouent un role dans la MAG-4, justifiant de nouvelles etudes prospectives.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p

Background The ACR/EULAR IgG4-related disease (IgG4-RD) provisional classification criteria were presented at the ACR conference in 2018. The performance of these criteria in a fully non-Asian cohort is unknown. Objectives To explore the performance of these provisional criteria in a cohort of Spanish patients with IgG4-RD. Methods Data were obtained from the Spanish IgG4-RD registry (REERIgG4) from October 2013 to December 2018, including 9 centers. Patients needed to fulfill almost 1 of the available diagnostic criteria sets (pathology consensus and/or comprehensive). N provisional ACR/EULAR classification criteria (PAECC) were applied based on the public information disclosed at the abovementioned meeting. Results One-hundred patients were included. Thirty-four (34%) were females, median age at diagnosis was 54.8 years (IQR 20.7). The ethnicity of the participants was: Caucasian 83%, Hispanic 12% and North-African/Middle-East 5%. Ninety-two percent were diagnosed with a biopsy. Regarding the diagnostic criteria, 85% met consensus pathology criteria and 94% comprehensive criteria. Fifty-one patients (51%) had systemic IgG4-RD involving >1 tissue. The most commonly involved tissues were: retroperitoneum (35%), lymph nodes (19%), orbit pseudotumor (18%), salivary glands (16%) and pancreas (14%). Forty-two patients (42%) had elevated serum IgG4. Seventy-one individuals (71%) met the PAECC including entry criteria, exclusion criteria with an inclusion criteria score equal or >19 points. From the 29 cases that did not meet the PAECC, 9 (31%) did not fulfill the first step (entry). Those patients had rarer organs involved as hypophysis, mesenterium or jaw. Eight patients (28%) met one of the exclusion items. Two had positive antineutrophil cytoplasmic antibodies, 2 steroid resistance, 2 double-stranded anti-deoxyribonucleic acid antibodies, 1 other specific autoantibodies, 1 eosinophilia and fever. None of them had evidence of active connective tissue disease, vasculitis, malignancy or infection. Finally, 16 of the patients who did not meet the PAECC (55%) had an inclusion criteria score under 19 points (median 12): 3 (19%) did not have a biopsy, 8 (50%) biopsies had partial reports, and 10 subjects (62.5%) had normal serum IgG4 levels. Six (38%) of them had involvement limited to the head and neck and 3 (19%) had retroperitoneal or aortic involvement. Conclusion Seventy-one percent of the Spanish patients participating in the REERIgG4 met the 2018 PAECC, while all of them met almost one of the previous diagnostic criteria. Populations with non-Asian ancestry might get lower scores, as they would make less points in significant domains (serum IgG4, pancreatic-biliary) or have presentations that may grant lower scores or exclusion. Enforcing complete pathology reports might increase the scores. Nevertheless, the new classification criteria are provisional and primarily intended for clinical trial recruitment, focusing in the most common manifestations. Therefore, the preexisting diagnostic criteria should be used for standard clinical purposes. Reference [1] Wallace Zs, Naden RP, Choi H. The 2018 ACR/EULAR Classification Criteria for igG4- Related Disease. Submitted 2018. Disclosure of Interests None declared

To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS).The GEAS-SS multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain.Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p0.001), lymphopenia (p0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p0.001) and cryoglobulins (p0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p0.001), immunosuppressants (p0.001), intravenous immunoglobulins (p=0.008) and rituximab (p0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved.13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.

Background IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored. Objectives To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes. Methods We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis. Results Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4-RD disease activity episodes. All treatments had high response rates but relapses and flares were common. Conclusions IgG4-RI is a promising outcome measure in IgG4-RD, but still in development. Treatment algorithms are ill defined. GC and rituximab are the drugs with more evidence available. Disease modifying anti-rheumatic drugs may have a role in IgG4-RD and warrant more prospective studies.