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The aim of this study was to evaluate the frequency of systemic treatment in a cohort of sarcoidosis patients and identify presenting clinical features as predictive factors of the need for systemic immunosuppressive therapy.Retrospective study of 342 patients diagnosed and followed-up from January 1999 to December 2019 in a University Hospital in Northern Spain. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria. A comparative analysis was performed between treated and untreated patients. Predictive factors of treatment prescription according to initial clinical manifestations were identified (multivariate analysis).Mean age at diagnosis was 47.7±15.1 years, with a slight female predominance (51.8%) and Caucasian majority (94.2%). The main clinical manifestation was thoracic involvement (88.3%). Extrathoracic manifestations were detected in 68.4% cases, mainly cutaneous (34.2%), articular (27.8%) and ocular (17.8%). A total of 207 (60.5%) patients required systemic treatment. Glucocorticoid therapy was the most widely used (60.5%). Conventional immunosuppressive therapy in 25.4%, more frequently MTX (21.9%). Biologic therapy was prescribed in 12.9%, especially adalimumab (9.1%). Male gender (OR: 1.65; 95%CI: 1.06-2.56), intrathoracic (OR: 2.41; 95%CI: 1.22-4.76), ocular (OR: 4.14; 95%CI: 2.01-8.52), parotid (OR: 1.60; 95%CI: 1.39-1.94), neurological (OR: 5.00; 95%CI: 1.68-14.84), and renal (OR: 1.59; 95%CI: 1.38-1.94) involvement were identified as risk factors associated with the need of systemic treatment.Most patients (60.5%) of sarcoidosis in our series required systemic therapy. An association between certain characteristics at initial presentation (male gender, lung, ocular, parotid, neurological and renal involvement) and the need of systemic treatment was identified.

Psoriasis of the external auditory canal (PsEAC) is often under-recognized. The aims of this study were to assess the prevalence of PsEAC, its association with a particular psoriasis subtype and its impact on quality of life (QoL). A prospective study was carried out in two Spanish university hospitals, enrolling consecutive patients who attended a consultation for psoriasis. The clinical features of psoriasis and PsEAC were recorded and the Dermatology Life Quality Index (DLQI) and Itch Numerical Rating Scale (Itch-NRS) were distributed to patients. Overall, 188 of 1000 patients (18.8%) included in the study had PsEAC, which was associated with severity of psoriasis, presence of inverse psoriasis and involvement of the scalp, nails and genitals, but not with obesity or psoriatic arthritis. PsEAC was the main reason for consultation in 27 patients, with itching being the main symptom. In this study, PsEAC had a prevalence of 18.8%. The occurrence of PsEAC was associated with poorer QoL, as measured by DLQI and Itch-NRS.

Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy therapeutic approaches to ILD treatment is an urgent need. The interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin initiates leukocyte extravasation and deletion of the corresponding gene (Selplg) induces a SSc-like syndrome with high incidence of ILD in aged mice.Aged PSGL-1 KO (SelplgPSGL-1 KO mice had increased numbers of CD45+ and CD45- cells, including alveolar and interstitial macrophages, eosinophils, granulocytes and NK cells, and myofibroblasts in bronchoalveolar lavage (BAL). CD45+ and CD45- cells expressing pro-inflammatory and pro-fibrotic cytokines were also increased. Lungs from PSGL-1 KO mice showed increased immune cell infiltration and apoptosis and exacerbated interstitial and peribronchial fibrosis. Targeted nanotherapy with LipHA+Ev decreased the myofibroblasts in BAL, cells producing proinflammatory and profibrotic cytokines, and the degree of lung inflammation at histology. LipHA+Ev treatment also decreased the severity of peribronchial and interstitial lung fibrosis, from moderate to mild levels.In PSGL-1 KO mice, targeted nanotherapy with LipHA+Ev was an effective treatment for SSc-ILD, reducing the number of inflammatory and fibrotic cells in BAL and reducing inflammation and fibrosis in lungs.

To characterize the demographic, genetic, clinical, and serological features of patients with anti-3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) in a region of northern Spain.Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521TC) single nucleotide polymorphism (SNP) in the SLCO1B1 gene.8 patients (5 women, 3 men) with a mean ± SD age of 64.9 ± 7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had been exposed to statins. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 and had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25‑hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population.In northern Spain, anti-HMGCR IMNM preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this disease.

In the few last years, a new family of drugs, anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), has been developed for migraine therapy. Anti-CGRP mAbs are highly effective, but the current limited experience with their use and their high-cost warrant establishing certain rules of use.The present review provides an overview of the management of migraine patients, especially those who are undergoing treatment with anti-CGRP mAbs.Thanks to new research focused on the pathophysiology of migraine, and the discovery that CGRP plays a key role in its etiopathogenesis, new drugs targeting CGRP have been developed. These drugs have led to a paradigm shift, anticipating new and stimulating possibilities in migraine treatment. While physicians and patients are full of expectation about the advantages of this new family of drugs, there are still obstacles to overcome in order to make the best use of them. It is essential to form multidisciplinary teams that can identify patients who will benefit from these therapies, conducting cost-effective treatments. The follow-up of these therapies in the coming years is paramount due to the lack of experience in the management of these drugs and the peculiarity of disease evolution in migraine patients.

Background The purpose of this study was to learn about the clinical practice of specialists who care for patients with giant cell arteritis, to verify whether they follow the diagnosis and treatment recommendations for this disease, and to identify areas for improvement. Methods A cross-sectional survey on clinical practice in 2019. The survey was completed by 167 physicians (64% rheumatologists, 27% internal medicine specialists, and 9% other specialists) who attended a course on updating giant cell arteritis treatment. We compared the clinical practice collected in the study with the latest recommendations approved by the European League Against Rheumatism (EULAR). Results The physicians surveyed cared for a median of 10 patients (interquartile range 6–30) with giant cell arteritis during their practice. As a diagnostic method, respondents used temporal artery biopsy (84%), temporal artery ultrasound (61%) or other imaging techniques (37%). As first-line therapy, respondents used high-dose glucocorticoids (at least 40 mg of prednisone, or equivalent, per day) (84%), glucocorticoids with methotrexate (7%) and glucocorticoids with tocilizumab (5%). The most frequent drugs used for relapse were methotrexate (37%) and tocilizumab (58%). Conclusion Our results indicate that the medical specialists surveyed follow the recent EULAR recommendations for giant cell arteritis diagnosis and therapy.

Resumen Antecedentes El proposito de este estudio fue conocer la practica clinica de especialistas que atienden a pacientes con arteritis de celulas gigantes, para comprobar si siguen las recomendaciones para el diagnostico y tratamiento de esta enfermedad e identificar areas de mejora. Metodos Encuesta transversal de practicas clinicas realizada en 2019. Ciento sesenta y siete medicos (64% reumatologos, 27% especialistas en medicina interna, 9% otros especialistas) que asistieron a un curso de actualizacion del tratamiento de la arteritis de celulas gigantes completo la encuesta. Comparamos la practica clinica recogida en el estudio con las ultimas recomendaciones aprobadas por la Liga Europea Contra el Reumatismo (EULAR). Resultados Los medicos encuestados atendian a una mediana de 10 pacientes (rango intercuartilico 6-30) con arteritis de celulas gigantes en su practica clinica. Como metodo de diagnostico, los encuestados utilizaron biopsia de arteria temporal (84%), ecografia de arteria temporal (61%) u otras tecnicas de imagen (37%). Como terapia de primera linea, los encuestados utilizaron glucocorticoides en dosis altas (al menos 40 mg de prednisona o equivalente por dia) (84%), glucocorticoides con metotrexato (7%) y glucocorticoides con tocilizumab (5%). Los farmacos mas utilizados para la recaida fueron el metotrexato (37%) y tocilizumab (58%). Conclusion Los resultados de esta encuesta indican que los medicos especialistas encuestados siguen las recomendaciones recientes de EULAR sobre diagnostico y tratamiento de la arteritis de celulas gigantes.

Autoimmune eye diseases (AED) are inflammatory eye conditions caused by dysregulation of the immune system at the ocular level. Among them, the most representative is noninfectious uveitis, which can be limited to the eye or associated with various systemic autoimmune diseases. Other conditions include peripheral ulcerative keratitis, Graves' orbitopathy, and some forms of optic neuropathy. Glucocorticoids are the cornerstone of treatment for most AEDs. However, conventional and/or biologic immunosuppressive drugs are often required to achieve clinical remission and reduce adverse events related to long-term glucocorticoid therapy.To summarize all the available evidence on the use of the anti-interleukin-6 tocilizumab receptor (TCZ) for the different AEDs.The heterogeneity of the reported studies and the relatively small number of prospective randomized clinical trials make it difficult to establish robust guidelines on the positioning of TCZ in the treatment of AEDs. However, based on our own experience and the growing number of published studies, we are in favor of the use of TCZ as an effective and safe alternative for patients with severe and/or refractory AEDs. We highlight the efficacy of TCZ in patients with optic neuropathy related to giant cell arteritis, noninfectious uveitis, and Graves´ orbitopathy.

Aims To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). Methods and results The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014–19. The treatment goal for BP was Conclusion We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). Methods: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted ‘yes’ (yes/no). Results: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients’ risk management. Conclusions: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs, Desarrollar recomendaciones sobre el uso de metotrexato (MTX) en combinación con medicamentos modificadores de la enfermedad (DMARD) biológicos (b) o sintéticos específicos (ts) en la artritis reumatoide (AR). Se seleccionaron 11 expertos en AR. Dos coordinadores formularon 13 preguntas sobre la terapia combinada de MTX con bDMARD o tsDMARD. Se realizó una revisión sistemática para responder las preguntas. Se establecieron criterios de inclusión y exclusión, así como las estrategias de búsqueda (se realizaron búsquedas en Medline, Embase y la Biblioteca Cochrane hasta enero de 2019). Dos revisores seleccionaron los artículos y recopilaron datos. Simultáneamente, se evaluaron los resúmenes de las reuniones EULAR y ACR. Con base en esta evidencia, los coordinadores propusieron recomendaciones preliminares que los expertos discutieron y votaron en una reunión de grupo nominal. El nivel de evidencia y el grado de recomendación se establecieron utilizando el Centro de Oxford para Medicina Basada en Evidencia y el nivel de acuerdo con un Delphi. El acuerdo se estableció si al menos el 80% de los expertos votaron «sí» (sí/no). La revisión sistemática recuperó 513 citas, de las cuales finalmente se incluyeron 61. Se generaron, votaron y aceptaron un total de 10 recomendaciones. El nivel de acuerdo fue muy alto en todas ellas y se logró en la primera ronda de Delphi. Las recomendaciones finales cubren aspectos como la dosis óptima de MTX, la estrategia de reducción o la gestión del riesgo de los pacientes. Este documento está destinado a ayudar a los médicos a resolver preguntas clínicas habituales y facilitar la toma de decisiones al tratar a pacientes con AR con MTX, en combinación con bDMARD o tsDMARD

C-reactive protein (CRP) is an acute-phase protein that is used as an established biomarker to follow disease severity and progression in a plethora of inflammatory diseases. However, its pathophysiologic mechanisms of action are still poorly defined and remain elusive. CRP, in its pentameric form, exhibits weak anti-inflammatory activity. On the contrary, the monomeric isoform (mCRP) exhibits potent pro-inflammatory properties in endothelial cells, leukocytes, and platelets. So far, no data exists regarding mCRP effects in human or mouse chondrocytes. This work aimed to verify the pathophysiological relevance of mCRP in the etiology and/or progression of osteoarthritis (OA). We investigated the effects of mCRP in cultured human primary chondrocytes and in the chondrogenic ATDC5 mouse cell line. We determined mRNA and protein levels of relevant factors involved in inflammatory responses and the modulation of nitric oxide synthase type II (NOS2), an early inflammatory molecular target. We demonstrate, for the first time, that monomeric C reactive protein increases NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 expression in human and murine chondrocytes. We also demonstrated that NF-kB is a key factor in the intracellular signaling of mCRP-driven induction of pro-inflammatory and catabolic mediators in chondrocytes. We concluded that mCRP exerts a sustained catabolic effect on human and murine chondrocytes, increasing the expression of inflammatory mediators and proteolytic enzymes, which can promote extracellular matrix (ECM) breakdown in healthy and OA cartilage. In addition, our results implicate the NF-kB signaling pathway in catabolic effects mediated by mCRP.

The aim of this study was to determine the role of endothelin-1 (ET-1), a molecule involved in multiple vascular and fibrosing abnormalities, as a biomarker of interstitial lung disease (ILD), as well as its use for the differential diagnosis between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD), using a large and well-defined cohort of patients with ILD. A total of 112 patients with IPF, 91 patients with AD-ILD (28 rheumatoid arthritis (RA), 26 systemic sclerosis, 20 idiopathic inflammatory myositis and 17 interstitial pneumonia with autoimmune features) and 44 healthy controls were included. ET-1 serum levels were determined by enzyme-linked immunosorbent assay. A significant increase in ET-1 levels was found in patients with IPF compared to controls. Likewise, AD-ILD patients also showed higher ET-1 levels than controls when the whole cohort was stratified by the type of AD. Similar ET-1 levels were found in IPF and AD-ILD patients, regardless of the underlying AD. Interestingly, increased ET-1 levels were correlated with worse lung function in IPF and RA-ILD patients. Our study supports that serum ET-1 may be useful as a biomarker of ILD, although it could not help in the differential diagnosis between IPF and AD-ILD. Moreover, ET-1 levels may be associated with ILD severity.

Background The incidence of sarcoidosis varies widely worldwide. The aim of this study was to estimate the incidence of sarcoidosis in a population-based cohort from northern Spain. Methods Patients diagnosed with sarcoidosis at Marques de Valdecilla University Hospital, corresponding to the central Cantabria that encompasses Santander city and the surroundings, between January 1999 and December 2019were assessed. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria as follows: compatible clinical and radiological presentation, histopathologic confirmation, and exclusion of other granulomatous diseases. Demographic and clinical data were collected. The incidence of sarcoidosis between 1999-2019 was estimated by sex, age, and year of diagnosis. Results A total of 234 patients were included, with a male/female ratio of 0.81. The mean age of the cohort at diagnosis was 48.43 ± 14.83 years and 129 (55.1%) were women. Incidence during the period of study was 3.58 per 100,000 populations (95% confidence interval: 3.13 – 4.07). No gender predominance was observed. An increase in age at diagnosis over time was found in the linear regression analysis. Thoracic affection was found in 180 patients (76.9%). Most common extra-thoracic areas affected were skin (34.2%), joints (30.8%) and eyes (15.4%). Conclusions The incidence of sarcoidosis estimated in this study was similar to that of other Mediterranean countries. No gender predominance was observed. Consistent with previous studies, male presented an incidence peak 10 years earlier than female. A second peak between ages 60-69 years was identified in both sexes.

We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was supported by European Union FEDER funds and `Fondo de Investigaciones Sanitarias (Grant PI18/00042) from 'Instituto de Salud Carlos III' (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Rio Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future) (Grant Number CM20/00006). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). BA-M is a recipient of a `Lopez Albo Post-Residency Programme funded by Servicio Cantabro de Salud. LL-G is supported by funds from IDIVAL (INNVAL20/06). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (Grant Numbers RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, project 734899-Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by ESF (`Investing in your future) (Grant Number CP16/00033)., Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between, European Commission, 'Instituto de Salud Carlos III' (ISCIII, Health Ministry, Spain) PI18/00042 Instituto de Salud Carlos III, European Social Fund (ESF) CM20/00006, RETICS Program (ISCIII) RD16/0012/0009, European Commission IDIVAL 18/01 INNVAL20/06, Servicio Cantabro de Salud, European Union FEDER fund RD16/0012/0014 PI17/00409, European Commission 734899 CP16/00033

To analyze the prevalence of metabolic syndrome (MetS) in patients with psoriatic arthritis (PsA) in a systematic literature review (SLR) and in the Spanish CArdiovascular in RheuMAtology (CARMA) cohort.A SLR and a subanalysis of the CARMA cohort were performed. In the SLR, PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov up to March 2019 were searched. Systematic literature reviews, clinical trials, and observational studies that analyzed the prevalence or frequency of MetS in PsA were analyzed. Two reviewers selected the articles, assessed the quality of the studies, and collected data, independently. In addition, data on sociodemographic characteristics and MetS in patients with PsA from the CARMA cohort were collected and analyzed. Comparative descriptive analysis was performed.The SLR included 18 articles, of moderate to high quality, with PsA patients of both sexes, with mean ages between 42 and 59 years. The rate of MetS varied from 23.5% to 62.9%. The most commonly used classification method was that of the National Cholesterol Education Program. Additionally, 724 PsA patients from the CARMA cohort were analyzed; 327 (45.4%) were women, 157 (21.8%) smokers, with a mean age of 51 years and a mean PsA disease duration of 9 years. Hypertension was the most common abnormal finding (66.8%), followed by hyperglycemia (42.6%) and hypertriglyceridemia (30.6%). Notably, 222 patients (30.6%) had MetS.The prevalence of MetS in PsA varies, depending on the definition. Whereas 23.5% to 62.9% of PsA patients have MetS, in the CARMA cohort almost a third of patients with PsA have MetS.

Introduction: Recent studies suggest a role of adipokines in the pathogenesis of hidradenitis suppurativa (HS). Omentin-1 and apelin are two recently identified adipokines that have been involved in the regulation of metabolic and inflammatory responses. Aim: To investigate serum omentin-1 and apelin levels in patients with HS and to assess their associations with metabolic parameters, disease severity and HS risk. Material and methods: This case-control study included 139 non-diabetic individuals (78 HS patients and 61 ageand sex-matched controls). Serum concentrations of omentin-1 and apelin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in all participants. Results: Serum omentin-1 concentrations were significantly higher in HS patients compared to controls, whereas apelin serum levels did not significantly differ between both groups. These differences in omentin-1 concentrations remained significant even after adjusting for age, sex, and body mass index (BMI). The results of logistic regression analysis showed that increased omentin-1 plasma levels were an independent risk factor for HS. However, we found no association between serum levels of both omentin-1 and apelin with HS severity. Conclusions: Our results show that patients with HS have raised omentin-1 serum levels, which are associated with HS risk.

We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was supported by European Union FEDER funds and `Fondo de Investigaciones Sanitarias´ (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant number CM20/00006). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud. LL-G is supported by funds from IDIVAL (INNVAL20/06). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (grant numbers RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, project 734899—Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by ESF (`Investing in your future´) (grant number CP16/00033)., Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1038/ s41598- 021- 91055-z, BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immunemediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV., European Union FEDER fund RD16/0012/0014, H2020 Programme 734899, Health Ministry, Servicio Cántabro de Salud, Servizo Galego de Saude, European Commission PI18/00042 EC, Research Executive Agency REA, Instituto de Salud Carlos III CP16/00033,PI17/00409 ISCIII, European Social Fund CM20/00006,RD16/0012/0009 ESF, European Regional Development Fund ERDF, Instituto de Investigación Marqués de Valdecilla PREVAL 18/01 IDIVAL, Servicio Gallego de Salud SERGAS

Clinical improvement following tocilizumab (TCZ) therapy in patients with large-vessel (LVV) giant cell arteritis (GCA) is well established. However, information on TCZ effect on imaging vascular activity is limited. We aimed to determine if clinical improvement correlated with reduction of vascular 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET/CT) scans.Observational study of patients with refractory LVV-GCA treated with TCZ who had a baseline and a follow-up 18F-FDG-PET/CT scan. For the visual analysis of 18F-FDG vascular uptake, a total vascular score (TVS) was defined, ranging from 0 to 15. Besides, a semiquantitative analysis was performed as a target to background ratio (TBR)= SUVmax thoracic aorta wall/SUVmax aortic vascular pool. The baseline and follow-up TVS and TBR were compared. Clinical and lab¬oratory outcomes were also assessed.We included 30 patients (24 women/6 men); mean age± standard deviation 65.7± 9.8 years. Baseline PET/CT scans were performed due to active disease at a median [interquartile range-IQR] of 1.5 [0.0-4.0] months before TCZ onset. Following TCZ therapy, 25 (83.33%) patients achieved clinical remission and reduction of 18F-FDG vascular uptake was also observed after a mean ± standard deviation of 10.8±3.7 months. TBR decreased from 1.70 ± 0.52 to 1.48 ± 0.25 (p=0.005) and TVS from 4.97±2.62 to 3.13±1.89 (p0.001). However, only 9 (30.0%) patients showed complete normalisation of TBR and only 3 (10%) normalisation of TVS. TBR and TVS showed a good correlation (r=0.576).Although most of LVV-GCA patients achieve clinical remission after TCZ therapy, less than one-third show normalisation of 18F-FDG vascular uptake.

Background Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory pathology that has been reported to affect principally the retroperitoneum, hepatobiliary system, salivary glands, orbital structures or lymph nodes. However, IgG4-RD with laryngeal involvement is a very rare entity. Our aims were to describe a case of subglottic stenosis as first and only manifestation of IgG4-RD and review the literature. A patient with IgG4-RD affecting the larynx that presented as subglottic stenosis is described. A MEDLINE database search of IgG4-RD cases with laryngopharyngeal manifestations was also conducted. A 30-year-old Caucasian woman was referred to a tertiary care hospital for dyspnea on exertion, which had been increasing for the last 4 months. Medical and surgical procedures revealed a subglottic stenosis, with a histological finding of IgG4 positive plasma cell infiltration. There was no evidence of other organ involvement. She was successfully treated with oral glucocorticoids and rituximab infusions. Glucocorticoids were rapidly tapered and the rituximab regimen was optimized, with no evidence of relapses. In the literature review, we found a total of 12 reported cases with laryngopharyngeal involvement, two of them with subglottic stenosis. IgG4-RD of the larynx is rare but should be considered after excluding more common disorders.

Objective.Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti–tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice.Methods.This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed.Results.There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1–5.4) to 3.7 (IQR 2.8–4.7,P< 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4–34.1) to 15.5 (IQR 10.1–25.7,P< 0.01), and C-reactive protein from median 1.9 (IQR 0.3–5.0) to 0.5 (IQR 0.1–2.2) mg/dL (P< 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2–86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial.Conclusion.Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.

Objective To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. Results We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) [ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5–15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. Conclusion In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.