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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.

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.

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.

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.

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.

Objective To investigate if the Systematic Coronary Risk Evaluation (SCORE) and the QRISK3 algorithms as well as the carotid ultrasound are useful predictors of cardiovascular (CV) events and death in a prospectively defined population-based rheumatoid arthritis (RA) inception cohort. Methods A set of 327 consecutive RA patients without history of diabetes, chronic kidney disease or CV events were studied by carotid ultrasound between 2012 and 2013. At that time, CV risk was calculated according to the modified EULAR systematic coronary risk evaluation (mSCORE) for RA. A five-year prospective follow-up study was conducted by survival analysis models. The EULAR mSCORE based on the 2015/2016 updated EULAR recommendations and the QRISK3 algorithms were retrospectively tested using baseline data. Results After 1,984.25 patient-years of follow-up, 23 had died and 27 had experienced CV events. Linearized mortality rate was 1.16/100 patient-years (95% confidence interval [CI]: 0.74--1.73). Adjusting for age, gender and disease duration, a model with carotid plaques (Hazard ratio [HR]: 6.10 [95% CI:0.74--50.0]; p = 0.09) and another model with carotid plaques and QRISK3 (HR for carotid plaques: 6.12 [95% CI: 0.74--50.5]; p = 0.09 and HR for each 1% in QRISK3: 1.03 [95% CI: 0.99--1.07], p = 0.11, respectively were the best predictors of death whereas a model with carotid plaques (HR: 5.25 [95% CI:1.41--19.50]; p = 0.01) and another model with carotid plaques and QRISK3 (HR for carotid plaques: 5.13 [95% CI: 1.36--19.3]; p = 0.02 and HR for each 1% in QRISK3: 1.03 [95% CI: 0.99--1.07], p = 0.12, respectively, were the best predictors of CV events. In contrast, the mSCORE was a weaker predictor of the risk of death or CV events. Conclusions The presence of carotid plaques predicts the development of CV events and death in patients with RA. The predictable capacity of carotid plaques and QRISK3 is higher than that of mSCORE in RA patients.

Purpose We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behcet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. Methods Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. Main outcome measures Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. Results The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.

To compare the efficacy of TNF inhibitors (adalimumab (ADA) and infliximab (IFX)) vs tocilizumab (TCZ) in patients with refractory cystoid macular edema (CME) due to Behçet's disease (BD).Multicenter study of patients with BD-associated CME refractory to conventional and/or biological immunosuppressive drugs. From a cohort of 177 patients treated with anti-TNF and 14 patients treated with TCZ, we selected those with CME at baseline. We analyzed the evolution of macular thickness (main outcome), best-corrected visual acuity (BCVA) and intraocular inflammation (Tyndall and vitritis) from baseline up to 4 years in the 3 groups mentioned.49 patients and 72 eyes with CME were included. ADA was used in 25 patients (40 eyes), IFX in 15 (21 eyes) and TCZ in 9 (11 eyes). No statistically significant baseline differences were observed between the 3 groups except for a lower basal BCVA in TCZ group and a higher basal degree of intraocular inflammation in ADA group. Most patients from all groups had received several conventional immunosuppressive drugs. In addition, most patients in the group of TCZ had also received anti-TNF agents. Biological therapy was used in monotherapy (n=8) or combined with conventional immunosuppressive drugs (n=41). Macular thickness progressively decreased in the 3 groups, with no signs of CME after 1 year of treatment. Similarly, BCVA improvement and inflammatory intraocular remission was achieved in all groups.Refractory CME associated with BD uveitis can be effectively treated either with ADA, IFX or TCZ. Furthermore, TCZ is effective in patients resistant to anti-TNF therapy.

To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA).This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected.888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs.Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.

Objective To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions Our results support the association of the HLA complex with the susceptibility to ASSD.

Objective 18F-FDG PET/CT has proved to be of potential value for early diagnosis of large-vessel vasculitis (LVV), which frequently involves the aorta. However, its role in the follow-up of these patients has not been well established. Our aim was to evaluate the contribution of 18F-FDG PET/CT in this clinical situation. Methods This study included 37 consecutive patients (28 women, 66.5 ± 9.9 years) with an initial 18F-FDG PET/CT positive for LVV and a mean ± standard deviation follow-up PET/CT of 7.5 ± 2.9 months after the initial scan. A semiquantitative analysis of aortic wall uptake was performed calculating the target-to-background ratio (TBR: aortic wall uptake divided by blood pool uptake). The initial and follow-up TBR as well as the clinical and laboratory outcome were compared. Results Overall, the mean TBR decreased from 1.7 ± 0.5 at the initial scan to 1.5 ± 0.3 at the time of follow-up (p = 0.0001). In the 21 patients who experienced clinical improvement following therapy the TBR also decreased from 1.8 ± 0.6 to 1.5 ± 0.3 (p = 0.0002). However, in the other 16 patients, in whom the treating physician considered that there was no clinical improvement following therapy, no statistically significant differences in TBR were found when data from the first and the follow-up PET/CT scans were compared (1.6 ± 0.3 versus 1.5 ± 0.3, p = 0.1416). Patients who experienced clinical improvement following therapy showed a nonstatistically significant higher TBR at the time of disease diagnosis (1.8 ± 0.6 versus 1.6 ± 0.3; p = 0.12). Conclusions The results obtained in the present study highlight the impact of 18F-FDG PET/CT on the management of patients with LVV. Professor Gonzalez-Gay´s research was supported by “Fondo de Investigación Sanitaria” (grant PI12/00060 and PI15/00525) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). His work is also partially supported by RETICS Programs RD12/0009 (RIER) from ISCIII (Spain) (RD16/0012/0009).

Polymyalgia rheumatica is an inflammatory disease that affects the shoulder, the pelvic girdles, and the neck, usually in individuals older than 50 years. Increases in acute phase reactants are typical of polymyalgia rheumatica. The disorder might present as an isolated condition or in association with giant cell arteritis. Several diseases, including inflammatory rheumatic and autoimmune diseases, infections, and malignancies can mimic polymyalgia rheumatica. Imaging techniques have identified the presence of bursitis in more than half of patients with active disease. Vascular uptake on PET scans is seen in some patients. A dose of 12·5-25·0 mg prednisolone daily or equivalent leads to rapid improvement of symptoms in most patients with isolated disease. However, relapses are common when prednisolone is tapered. Methotrexate might be used in patients who relapse. The effectiveness of biological therapies, such as anti-interleukin 6, in patients with polymyalgia rheumatica that is refractory to glucocorticoids requires further investigation. Most population-based studies indicate that mortality is not increased in patients with isolated disease.

Objective To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE). Methods We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients. Results The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio=5.0); mean age at diagnosis was 34 years (range: 14–56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis. Conclusions While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE.

Summary Objective Lipocalin-2 (LCN2) is an adipokine that was first identified in neutrophil granules. In the last years it was recognized as a factor that could impair chondrocyte phenotype, cartilage homeostasis as well as growth plate development. Both pro-inflammatory cytokines and glucocorticoids (GCs) modulate LCN2 expression. Actually, GCs were found to be LCN2 inducers, suggesting that part of the negative actions exerted by these anti-inflammatory drugs at cartilage level could be mediated by this adipokine. So, in this study we wanted to investigate whether corticoids were able to act in synergy with IL-1 in the induction of LCN2 and the signaling pathway involved in this process. Materials and methods For the realization of this work, ATDC5 mouse chondrogenic cell line was used. We determined the mRNA and protein expression of LCN2 by real-time reverse transcription-polymerase chain reaction (RT-qPCR) and western blot respectively, after GC or mineralcorticoid treatment. Different signaling pathways inhibitors were also used. Results GC and mineralcorticoid were able to induce the expression of LCN2 in ATDC5 cells. Interestingly, both corticoids synergized with IL-1 in the induction of LCN2. The effect of these corticoids on the expression of LCN2 occurred through GC or mineralcorticoid receptors and the kinases PI3K, ERK1/2 and JAK2. Conclusions Prolonged use of corticoids may have detrimental effects on cartilage homeostasis. Based on our results, we conclude that corticoids could increase the negative actions exerted by IL-1 by increasing the expression of LCN2.

Objective Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. Methods Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. Results 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p=0.002). Conclusion Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Background: The impact of chronic inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we systematically identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Findings: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Patients were on treatment with glucocorticoids (40%), conventional synthetic disease modifying antirheumatic drugs (csDMARD) (57%), targeted synthetic or biological (ts/bDMARD) (23%), or other immunosuppressants (12%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31·6% in the rheumatic and 28·1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe were increased age (OR 5·31; CI 3·14-8·95), male sex (2·13; CI 1·35-3·36) and having an AI/IMID (OR 1·98; CI 1·15-3·41). Interpretation: In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19. Funding Statement: The RIER network was supported by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (RD16/0012 RETICS program) and cofinanced by the European Regional Development Fund. Declaration of Interests: None of the authors have competing interests to declare. Ethics Approval Statement: The study was approved by Comite de Etica de la Investigacion del Hospital Universitario 12 de Octubre, CEIm number: 20/160.

Background Interstitial lung disease (ILD) is a serious complication that represents the second leading cause of death in patients with rheumatoid arthritis (RA). Treatment of RA-ILD remains controversial. The absence of randomized clinical trials and specific ACR or EULAR therapeutic guidelines makes it difficult to establish solid therapeutic recommendations on this issue. In this scenario, real-world data is especially valuable. Objective To review the literature evidence on the efficacy and safety of abatacept (ABA) for the treatment of rheumatoid arthritis (RA) with associated interstitial lung disease (ILD), given its clinical relevance and the lack of consensus on its therapeutic management. Methods PUBMED and EMBASE were searched from the date of approval of ABA to the end of 2020 using a combination of RA, ILD and ABA terms following PRISMA guidelines. Identified studies were evaluated by two independent investigators. Results Nine original studies (1 case series and 8 observational studies) were selected for inclusion in the systematic review. No randomized trial or meta-analysis were identified. The mean age of patients ranged from 61.2 to 75 years and the mean RA duration varied from 7.4 to 18 years. Subcutaneous ABA (74.5%–91%) predominated in combination with conventional synthetic DMARDs (csDMARDs) (58%–75%), and it was used as first-line biologic agent in 22.8%–64.9% of the patients. The mean course of ILD ranged from 1 to 6.7 years, being usual and nonspecific interstitial pneumonia the most frequent patterns. Improvement or stabilization of ILD imaging (76.6%–92.7%) and FVC or DLCO (>85%) was described after a mean follow-up of 17.4–47.8 months, regardless of the pattern of lung involvement, being more remarkable in patients with shorter evolution of ILD. ABA led to significantly lower ILD worsening rates than TNF inhibitors (TNFi) and was associated with a 90% reduction in the relative risk of deterioration of ILD at 24 months of follow-up compared to TNFi and csDMARDs. Combination with methotrexate may have a corticoid-sparing effect. No unexpected adverse events were identified. Conclusions Current evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD. It would be highly desirable to develop prospective randomized controlled studies to confirm these findings.

Cardiovascular disease (CV) is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). This is the result of an accelerated atherosclerotic process. Adequate CV risk stratification has special relevance in RA to identify patients at risk of CV disease. However, current CV risk screening and management strategies underestimate the actual CV risk in RA. Consequently, the search for additional tools that may help to identify those patients at high CV risk has become a key objective in the last years. In this regard, non-invasive surrogates, such as carotid ultrasonography, have been found to be excellent predictors of future CV events. In addition, several studies have revealed the relevance of a genetic component in the development of CV disease in RA patients. Besides an association with HLA-DRB1* shared epitope alleles other gene polymor-phisms located inside and outside the HLA seem to influence the risk of cardiovascular disease in RA. Moreover, serum levels of some metabolic syndrome-related biomarkers, adipokines such as adiponectin and biomarkers of endothelial cell activation and inflammation such as Osteoprotegerin and Asymmetric dimethylarginine have recently been found useful for the prediction of CV disease in these patients. An update of the current knowledge on these potential markers, especially focused on new genetic and serological biomarkers is shown in this review. (C) 2016 The Authors. Published by Elsevier B.V., This work was supported by European Union FEDER funds and "Fondo de Investigation Sanitaria" (grants PI06/0024, PS09/00748, PI12/00060 and PI15/00525) from 'Institut de Salud Carlos III' (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from 'Instituto de Salud Carlos III' (ISCIII, Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. We wish to specially thank Mercedes Garcia-Bermudez, Begona Ubilla, Veronica Mijares, Patricia Fuentevilla Rodriguez, Virginia Portilla Gonzalez and all the clinicians from Spanish National Health Care system that have been involved in our studies.

Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.

Cardiovascular (CV) morbidity and mortality are increased in patients with active, untreated rheumatoid arthritis (RA), despite lower levels of total and low-density lipoprotein cholesterol reported in individuals with active RA compared with those without RA. Alterations in non-traditional lipid assessments, such as high-density lipoprotein (HDL) function and HDL-associated proteins, have been described in patients with active RA, including elevated HDL-associated serum amyloid A and decreased paraoxonase-1 activity. We review changes in both traditional lipoprotein concentrations and non-traditional lipoprotein assessments in multiple studies of treatment with disease-modifying antirheumatic drugs (DMARDs), including non-biologic and biologic DMARDs and tofacitinib. In addition, data from a recently published clinical trial with tofacitinib that describe a potential mechanism for suppression of cholesterol levels in active RA patients are reviewed. Finally, CV event data from various studies of DMARDs are presented, and the current management of RA patients with regard to the CV risk is reviewed.

Objectives To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. Methods Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. Results A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13−76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4−8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range—IQR) 0.5 (0−2) versus 0 (0−0) ( p = 0.003), vitritis 0 (0−1.25) versus 0 (0−0) ( p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) ( p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0−30)mg at the onset of the anti-TNF-α therapy to 0 (0−0)mg at 2 years ( p = 0.02). Significant reduction was also achieved in the immunosuppressive load. Conclusion Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.

Standard therapeutic schemes for vasculitis are usually associated with numerous side effects and uneven clinical response. However, recent advances in understanding of the pathogenesis of these systemic diseases have resulted in the development of a group of biologic agents potentially useful in patients with vasculitis. Thus, anti-tumor necrosis factor-α drugs may be effective in patients with refractory Kawasaki disease but have failed to do so in giant cell arteritis, and their role in Takayasu arteritis is yet unclear. Preliminary reports on the use of the anti-IL6-receptor antibody, tocilizumab, in large-vessel vasculitis have been encouraging. Interferon alpha has showed positive results in hepatitis B virus-associated polyarteritis nodosa, and hepatitis C virus-induced cryoglobulinemia. Early experience with rituximab in several types of vasculitis has been quite promising, but must be confirmed in ongoing randomized clinical trials. The development of new biologic targeted therapies will probably open a hopeful future for patients with vasculitis.

Purpose: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behcet disease (BD) who achieved remission after the use of this biologic agent. Design: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Subjects: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. Methods: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Main Outcome Measures: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. Results: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean +/- standard deviation follow-up of 34.7+/-13.3 and 26+/-21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). Conclusion: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and costeffective. (C) 2018 by the American Academy of Ophthalmology

Resume But Evaluer le risque cardiovasculaire (CV) chez les patients atteints de rhumatisme psoriasique (RP) sans maladie CV cliniquement evidente ni de facteurs de risque CV classiques, selon le diagramme SCORE suivant les recommandations de l’EULAR. Methodes Quatre-vingt patients atteints de RP sans antecedent d’evenement CV ni de facteurs de risque d’atherosclerose et 80 controles ont ete inclus. Les donnees demographiques, anthropometriques et clinico-serologiques ont ete evaluees. L’indice national Calibrated Systematic Coronary Risk Evaluation (SCORE) a ete calcule et l’association entre ce SCORE et les donnees clinico-serologiques a ete analysee. Resultats Les patients atteints de RP avaient des parametres de l’inflammation et des valeurs de SCORE plus eleves que les controles (1,99 ± 3,52 vs 1,0 ± 1,74 ; p = 0,028). Selon les definitions SCORE, 71 (89 %) patients avaient un risque CV faible/intermediaire et 9 (11 %) etaient en dessus de la limite du risque eleve. Dans le groupe temoin, 76 (95 %) avaient un risque faible/intermediaire et 4 (5 %) avaient un risque eleve. Cependant, il n’y avait pas de difference en termes de stratification du risque CV entre les deux groupes (p = 0,148). Les patients atteints de RP avec un risque CV eleve avaient une duree d’evolution de la maladie plus elevee (0,001) et un taux plus eleve de triglycerides (p = 0,009). Les patients atteints de RP presentaient une correlation significative entre les valeurs SCORE et la duree d’evolution de la maladie (β = 0,185 ; p = 0,0001) et avec les niveaux moyens annuels de C-reactive protein (CRPm), β = 2,38 ; p = 0,014. Conclusion L’evaluation du risque CV chez les patients atteints de RP sans atteinte CV evidente cliniquement et sans facteurs classiques d’atherosclerose pourrait etre sous-estimee si l’on n’utilise que le diagramme SCORE. Chez ces patients, la duree d’evolution de la maladie et la CRPm pourraient aider a obtenir une meilleure stratification des facteurs de risque CV.

The term large vessel vasculitidis includes two distinct clinical entities: Takayasu's arteritis and giant cell arteritis. Takayasu's arteritis mainly affects children and women under 40 years, affecting the aorta and its major branches. Its incidence in Southern Europe is low. Giant cell arteritis is the most common vasculitis in those 60. Its incidence in the European population is greater than that of Takayasu's arteritis. It mainly affects the extracranial vessels, especially those derived from the carotid artery. Both conditions are characterized by inflammation of the vessel wall, this causing structural damage and the expression of different clinical manifestations. The treatment of choice of both conditions is based on high-dose glucocorticoids associated, in some cases, to immunosuppressants. Biologic agents have been reserved for cases refractory to conventional therapies.

Resumen Las vasculitis de grandes vasos incluyen las arteritis de Takayasu y la de celulas gigantes. La arteritis de Takayasu afecta a ninos y mujeres menores de 40 anos, presenta una baja incidencia en el sur de Europa, y afecta principalmente a la aorta y sus ramas principales. La arteritis de celulas gigantes es la vasculitis mas frecuente en los mayores de 60 anos, con una incidencia mayor que la arteritis de Takayasu en la poblacion europea. Afecta principalmente los vasos extracraneales, especialmente, los derivados de la carotida. Ambas entidades presentan inflamacion a nivel de la pared vascular, lo que ocasiona el dano estructural y la expresion de un amplio espectro de manifestaciones clinicas. El tratamiento de eleccion de ambas entidades se basa en el uso de glucocorticoides a dosis elevadas asociados con frecuencia a inmunosupresores. La utilizacion de tratamientos biologicos se reservara para los casos refractarios al tratamiento convencional.

Introduction Rheumatoid arthritis (RA) is an inflammatory disease associated with increased cardiovascular (CV) mortality. A recent study has disclosed association between NFKB1 -94ATTG ins/del polymorphism and higher risk of coronary heart disease in healthy Caucasians. Because of that, we assessed the influence of this polymorphism in the risk of CV disease in RA patients. Material and methods 1437 Spanish patients with RA were genotyped for the NFKB1 -94ATTG ins/del polymorphism. Two hundred and seventy-one of them (18.8%) had experienced CV events. Results After adjusting for sex, age at RA diagnosis and traditional CV risk factors RA patients carrying the NFKB1 del/del genotype had higher risk of CV events than those with ins/ins genotype (Hazard ratio [HR] = 1.76, 95% CI: 1.05–2.97, p = 0.03), while heterozygous patients had an intermediate (but non-significant) risk (HR = 1.31, 95% CI: 0.90–1.92, p = 0.16). Conclusion Our results suggest that NFKB1 -94ATTG ins/del polymorphism is associated with CV disease in patients with RA.

Resumen Introduccion y objetivos La granulomatosis con poliangeitis (GPA), previamente llamada granulomatosis de Wegener, es una vasculitis de pequenos vasos que con frecuencia se asocia a manifestaciones clinicas de cabeza y cuello, y en ocasiones constituyen los sintomas de presentacion de la enfermedad. El objetivo de nuestro estudio fue identificar la afeccion otorrinolaringologica asociada a dicha enfermedad y proponer un protocolo diagnostico de los pacientes con sospecha clinica o confirmada de la misma. Pacientes y metodos Se realizo un estudio retrospectivo descriptivo que incluyo los pacientes diagnosticados de GPA que recibieron asistencia por el Servicio de Otorrinolaringologia de un hospital publico de tercer nivel de Cantabria. El periodo de inclusion fue de 20 anos. Se recogieron de la historia clinica diferentes variables clinicas concernientes al area de cabeza y cuello. Resultados Veinticinco pacientes con edades comprendidas entre 30 y 81 anos de edad fueron incluidos en nuestro estudio. El 88% de los mismos presentaron manifestaciones otorrinolaringologicas en algun momento de la evolucion de la enfermedad, y en un 28% constituyeron la forma de presentacion de la misma. Los sintomas nasosinusales fueron los mas frecuentes (52%), seguido de los otologicos (32%). Un paciente desarrollo un carcinoma de nasofaringe 3 anos despues del tratamiento con ciclofosfamida. Conclusiones Los pacientes con GPA presentan con frecuencia manifestaciones clinicas de cabeza y cuello. Es necesario realizar una exploracion sistematica otorrinolaringologica en los pacientes con sospecha o diagnostico confirmado de GPA, tanto para contribuir al diagnostico de la enfermedad, si esta no estuviese confirmada, como para establecer el grado de afeccion sistemica de pacientes con esta vasculitis.

Introduction Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. IL-6 is a key mediator of inflammation in RA. A recent study showed an association between IL6 -174 G/C gene polymorphism and cardiovascular (CV) disease in UK individuals with RA. To confirm this association we assessed the influence of three IL6 gene polymorphisms in the risk of CV disease in a large series of patients with RA. Material and methods We studied 1250 Spanish patients with RA. Besides genotyping the traditional single nucleotide polymorphism (SNP) promoter -174G/C (rs1800795), we assessed another two SNPs (rs2069827 and rs2069840) located in the IL6 gene that were selected by SNP-tagging. Results Two-hundred and twenty (17.6%) of the 1250 patients experienced CV events. No significant differences in the genotype, allele and haplotype frequencies between RA patients with and without CV events were observed. Conclusion Our results do not confirm in a Spanish population the association of IL6 gene with CV disease in RA previously reported in the UK.

To further explore the potential role of chemokines in giant cell arteritis (GCA), we have studied whether the CCR5/Δ32CCR5 polymorphism is implicated in the susceptibility to the disease and its specific features. A total of 352 Spanish patients with biopsy-proven GCA and 479 matched controls were assessed. DNA was obtained from peripheral blood. Samples were genotyped by PCR with specific primers spanning the 32-bp deletion region. No statistically significant difference in the Δ32CCR5 allele frequency between GCA patients (6.1%) and controls (6.8%) was observed (p = 0.58). This was also the case when the CCR5 /Δ32CCR5 genotype distribution was assessed (p = 0.49). The Δ32CCR5 allele frequency did not differ between patients with or without specific manifestations of the disease, such as polymyalgia rheumatica, visual ischemic manifestations, or irreversible occlusive disease. Hence, our results do not support a potential influence of Δ32CCR5 in the susceptibility to or clinical spectrum of GCA.

Giant cell arteritis (GCA) is a complex polygenic disease in which more than one genetic locus is likely to contribute to disease susceptibility and clinical expression. In the present study, we have analyzed for first time the implication of rs13277113 and rs2736340 variants from the C8orf13-BLK gene region in the susceptibility to GCA. A total of 220 biopsy-proven GCA patients and 486 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the C8orf13-BLK region rs13277113 and rs2736340 using a predesigned TaqMan allele discrimination assay. No significant differences in the genotype distribution between GCA patients and controls for the rs13277113 and rs2736340 C8orf13-BLK gene variants were found. GCA patients were also stratified according to the presence of specific clinical features of the disease. In this regard, the allele A of the rs13277113 variant was overrepresented in patients with severe ischemic manifestations compared with patients without severe ischemic manifestations (p = 0.04; OR =1.65; 95% CI = 0.99–2.78). In conclusion, our results do not support a major implication of the C8orf13-BLK gene region in susceptibility to GCA. However, a potential implication of the rs13277113 variant in the development of severe ischemic complications may exist.

Objective To establish whether serum uric acid concentration correlates with carotid intima-media wall thickness (IMT) in a cohort of psoriatic arthritis (PsA) patients without overt cardiovascular (CV) disease or classic CV risk factors who attended a community hospital. Methods A series of 52 PsA patients were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were measured in the right common carotid artery. A correlation between serum uric acid concentration and carotid IMT was assessed and receiver operating characteristic curves to evaluate the ability of serum uric acid to predict carotid IMT > 0.90 mm and carotid plaques were performed. Results PsA patients with hyperuricemia ( n = 6 [11.5%]) had greater carotid IMT (mean ± standard deviation: 0.89 ± 0.20 mm) than those without hyperuricemia ( n = 46 [89%]; 0.67 ± 0.16 mm) ( P = 0.01). Patients with carotid IMT 0.90 mm; P for trend=0.02). A significant correlation between carotid IMT and serum uric acid concentration was observed ( r = 0.337; P = 0.01). High serum uric acid levels were associated with an increased risk of having carotid IMT > 0.90 mm (Odds ratio=2.66 [95% confidence interval: 1.08-6.53], P = 0.03, area under receiver operating characteristic curve: 0.80) or with the presence of carotid plaques (Odds ratio=1.85 [95%; confidence interval: 1.01-3.38], P = 0.05, area under receiver operating characteristic curve: 0.72). Conclusions In PsA patients without clinically evident CV disease there is a correlation between serum uric acid concentration and subclinical atherosclerosis.

Audiovestibular manifestations in systemic vasculitis Abstract Systemic vasculitides constitute a heterogeneous group of diseases with frequent overlapping in their clinical findings and the size of the vessels involved. They may be primary or secondary to other diseases. Their common characteristic is the inflammation of blood vessels, giving rise to ischaemia. In the present article, we have reviewed the most common audiovestibular features that may be observed in patients with systemic vasculitides. Audiovestibular manifestations may be the first symptom of a systemic vasculitis. Audiological manifestations include sudden hearing loss and progressive sensorineural hearing loss. Vertigo and nystagmus are vestibular symptoms that may be observed in several systemic vasculitides. Vestibular loss in caloric test, abnormal

Objective: To evaluate the prevalence of serum antibodies against hepatitis C virus and other infectious agents in a large cohort of well-characterized patients with autoimmune diseases (AID). Methods: We utilized 1322 sera from patients with 18 different AID and 236 sera from healthy controls from the same countries and with similar age and sex distribution. All sera were tested for the presence of serum anti-hepatitis C virus (HCV) antibodies as well as antibodies directed at other infectious agents and autoantibodies. Results: Anti-HCV antibody was detected in 115/1322 (8.7%) of patients with AID and 0.4% of matched healthy controls (P less than 0.0001). The prevalence of anti-HCV antibody was significantly higher in 7/18 different AID (i.e. cryoglobulinemia, mixed cryoglobulinemia pemphigus vulgaris, vasculitis, secondary anti-phospholipid syndrome, Hashimoto's thyroiditis, and inflammatory bowel disease) compared to controls. Patients with AID and serum anti-HCV positivity had an increased prevalence of antibodies against hepatitis B virus, Toxoplasma gondii and Cytomegalovirus as opposed to a lower frequency of serum autoantibodies. Conclusions: The enhanced prevalence of anti-HCV serum antibodies in AID may suggest a role for HCV in tolerance to breakdown, similarly to its established role in mixed cryoglobulinemia. This immune mediated effect does not rule out the role of other infectious agents. © 2009.

To establish whether carotid intima-media wall thickness (IMT) may be a good predictor for the development of cardiovascular (CV) events in patients with rheumatoid arthritis (RA).A series of 47 RA patients who at the time of recruitment did not have traditional CV risk factors or CV disease were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were measured in the right common carotid artery. Then, a prospective assessment of the CV outcome was performed over a 5-year period. Logistic regression models and receiver operating characteristic curves were performed to evaluate the ability of different variables to predict CV events.Carotid IMT was greater in RA patients who over the extended follow-up experienced CV events (1.01 +/- 0.16 mm) compared with the remaining RA patients who did not have CV complications (0.74 +/- 0.12 mm) (P0.001). Also, carotid IMT categorized in quartiles was strongly associated with CV events. In this regard, none of the patients with carotid IMT less than 0.77 mm had CV events. However, 6 of the 10 patients with carotid IMT greater than 0.91 mm experienced CV events (P value for the trend0.001). Carotid IMT yielded a high predictive power for the development of CV events over the 5-year follow-up period. The area under the receiver operating characteristic curve was 0.93 for a model that only included carotid IMT and 0.90 for carotid plaque.The results from the present study support the use of carotid ultrasonography as a predictor of CV events in RA.

To investigate the potential association between levels of the erythrocyte sedimentation rate (ESR) and specific clinical features of giant cell arteritis (GCA), in particular, visual loss, in a series of consecutive patients diagnosed with GCA at the reference hospital for a well-defined population.The case records of all biopsy-proven GCA patients diagnosed at the Department of Medicine of Hospital Xeral-Calde (Lugo, Northwest Spain) between 1981 and 2006 were reviewed. Clinical information and laboratory data including ESR at the time of disease diagnosis were assessed.Only 10 (3.6%) of the 273 patients had ESR50 mm/h. Significant differences in the frequency of visual ischemic complications according to different levels of ESR were observed (P = 0.01), mainly due to an increased frequency of visual ischemic events in patients with ESR between 70 and 100/h at the time of disease diagnosis. Twenty-five (21%) of 120 individuals with ESR values ranging between 70 and 100 mm/h experienced permanent visual loss compared with only 10 (7%) of the remaining 153 patients (P = 0.0005; OR: 3.76 [95% CI: 1.73-8.19]). An ESR between 70 and 100 mm/h was the best predictor of visual ischemic complications (OR = 2.29 [95% CI: 1.16-4.55]; P = 0.03) and irreversible visual loss (OR = 3.58 [95% CI: 1.51-8.49]; P = 0.004).The results from this study show an increased risk of severe ocular complications in biopsy-proven GCA patients presenting with an ESR between 70 and 100 mm/h. Prompt initiation of corticosteroid therapy and close follow-up of these patients is recommended to minimize the risk of irreversible visual loss.

Objective To investigate the potential association between giant cell arteritis (GCA) and cancer in a series of consecutive patients diagnosed with biopsy-proven GCA over a 25-year period at the single reference hospital for a well-defined population. Methods The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between January 1, 1981 and December 31, 2005 were reviewed. Information on cancer and cause of death over the extended follow-up was assessed. In all cases the presence of cancer was histologically confirmed. Results Cancer was found in 39 (15.3%) of the 255 GCA patients. Although 7 (18%) of the 39 patients had cancer either at the time or within the first 12 months after GCA diagnosis, the standardized mortality ratio (SMR) due to cancer in patients with biopsy-proven GCA showed no increase (overall SMR 1.06 [0.65-1.60]; men, 0.81; women, 1.50). The time interval between GCA diagnosis and cancer diagnosis was 5.2 ± 3.8 years (median 4.2 years; interquartile range: 3-7 years). When multivariate analysis adjusted by age and sex was performed, only the presence of dysphagia (adjusted hazards ratio (HR) = 3.90; P = 0.04), abnormal temporal artery on physical examination (adjusted HR=4.61; P = 0.04), and anemia at the time of GCA diagnosis (adjusted HR=3.39; P = 0.01) were associated with an increased risk of cancer over the extended follow-up. Conclusion The results from this series do not support an overall increase of mortality due to cancer in GCA.