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Background: Antisynthetase syndrome (ASyS) is characterised by the association of inflammatory myopathy, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon (RP) or mechanic's hands (MH), with the presence of anti-aminoacyl-tRNA-synthetase antibodies (anti-ARS). It has been suggested that different anti-ARS may be associated with distinct clinical pictures., Objective: To characterise the clinical and immunological features of a multicentric nationwide cohort of ASyS patients., Methods: This is a multicentre retrospective cohort study including patients with ASyS from nine Portuguese rheumatology centres. Data on patients' demographics, signs and symptoms, laboratory results, pulmonary imaging findings and treatment with immunomodulators were collected. Comparison between patients with different anti-ARS antibodies was made using the Chi-square test for categorical variables and Student's t-test or Man-Whitney test for continuous variables, considering anti-Jo1 positive patients as the reference group., Results: Seventy patients were included (70% female) with a median age in years at disease onset of 52 (15-75) years and median follow-up time of 3 years (range 0-32). The three most common clinical manifestations were ILD (n=53, 75.7%), followed by arthritis (n=43, 61.4%) and myositis (n=37, 52.9%). Forty-three patients were positive for anti-Jo1 (61.4%), 11 for anti-PL12 (15.7%), 10 for anti-PL7 (14.3%), 4 for anti-EJ (5.7%), and 2 for anti-OJ (2.9%) antibodies. Antibody co-positivity with anti-Ro52 antibodies was found in 15 patients (21.4%) and was more prevalent in anti-Jo1 patients. ILD prevalence was similar in the different anti-ARS subgroups, without statistically significant differences. Patients positive for anti-PL7 antibodies had significantly lower risk of presenting arthritis (p =< 0.05) and those positive for anti-PL-12 antibodies had a significantly lower risk of presenting myositis than the reference group of anti-Jo1 positive patients (p =< 0.05). RP was more frequently found in patients positive for anti-PL-12 than in anti-Jo1-positive patients (p =< 0.05). Malignancies were reported in four (5.7%) patients, none of whom were anti-Ro52-positive, and one of such patients had a double malignancy. Only three deaths were reported. Corticosteroids were the most frequently prescribed therapy and the use of immunosuppressive drugs was decided according to the type of predominant clinical manifestation., Conclusion: The three most common clinical manifestations were ILD, followed by arthritis and myositis. Patients positive for anti-PL7 antibodies had significantly lower risk of presenting arthritis and those positive for anti-PL-12 antibodies had a significantly lower risk of presenting myositis than the reference group of anti-Jo1 positive patients. RP was more frequently found in patients positive for anti-PL-12 than in anti-Jo1-positive patients. Corticosteroids were the most frequently prescribed therapy. These results are generally concordant with data retrieved from international cohorts.

Objective: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR)., Methods: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists., Results: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission., Conclusion: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Background: Axial spondyloarthritis (axSpA), particularly ankylosing spondylitis was historically considered a male's disease and has been under-recognized in women. Emerging evidence reveals sex differences in pathophysiology, disease presentation and therapeutic efficacy., Objective: To identify differences between sexes in a Portuguese cohort of patients with axSpA regarding clinical manifestations, disease activity, functional capacity, patient related outcomes and presence of sacroiliitis on x-ray or magnetic resonance imaging., Methods: Patients with ≥18 years fulfilling the ASAS- Assessment of Spondyloarthritis International Society classification criteria for axSpA registered in the electronic Rheumatic Diseases Portuguese Register (Reuma.pt) were included in this multicentric cross-sectional study. Sociodemographic data, clinical features and imaging were collected from the first record in Reuma.pt. These variables were compared between sexes using Mann-Whitney test and Chi-Square test. Variables with a significant association with variable sex were considered in the multiple variable analysis to adjust the sex effect on the outcome variables. Statistical analysis was performed with R version 4.0.2 and p <0.05 was considered statistically significant., Results: A total of 1995 patients were included, 1114 (55.9%) men and 881 (44.1%) women. Men had an earlier disease onset (25.1 vs 28.4, p <0.001), were younger at diagnosis (26.9 vs 30.4, p<0.001) and were more frequently smokers (32.1% vs 15.7%, p <0.001). Comparing to women, men had worse Bath Ankylosing Spondylitis Metrological Index scores (4.0 vs 3.4, p<0.001), higher levels of C-Reactive Protein (10.5 vs 6.9 mg/L, p <0.001) and were more often Human Leukocyte Antigen-B27 positive (67.8% vs 54%, p <0.001). In contrast, women more frequently had inflammatory bowel disease (8.8% vs 4.9%, p =0.004), higher levels of erythrocyte sedimentation rate (25.0 vs 21.0mm/h, p=0.003) and worse patient-related outcomes- Bath Ankylosing Spondylitis Disease Activity Index (5.7 vs 4.5, p<0.001), Patient Global Assessment (60.0 vs 50.0, p <0.001) and fatigue (6.2 vs 5.0, p <0.001)., Discussion: In this large multicentric study from a Portuguese axSpA cohort, we confirmed sex differences in patients with axSpA. This work brings awareness to these differences, resulting in less underdiagnosis and misdiagnosis, optimizing treatment strategies, and improving outcomes in axSpA.

Competing Interests: The authors declare no conflict of interest.

Objectives: To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA)., Methods: Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima-media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared., Results: 49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (-0.34, -0.37 and -0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012)., Conclusions: Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID-19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management., Methods: In this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjögren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237., Findings: Between June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46-67]; 2239 [73·9%] women and 789 [26·1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5·5% [95% CI 4·7-6·4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4·0% [95% CI 3·4-4·8]) of 3028 patients, of whom 24 (19·7%) were admitted to hospital and four (3·3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1·18, 95% CI 1·05-1·33; p=0·0063), and higher numbers of recent disease flares (1·27, 1·02-1·58; p=0·030), whereas use of biological therapy was associated with reduced risk (0·51, 0·32-0·82; p=0·0057). At least one disease flare occurred in 654 (21·6%) of 3028 patients. Over the study period, 519 (20·6%) of 2514 patients had treatment changes, of which 125 (24·1%) were due to the pandemic., Interpretation: This study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic., Funding: Pfizer, Sanofi, Amgen, Galapagos, and Lilly., Competing Interests: DS has received grant or research support from Amgen, Galapagos, Sanofi, Janssen, Lilly, Pfizer, Roche Chugai, Mylan, GlaxoSmithKline, and Hifibio, and consulting fees from AbbVie, Amgen, Janssen, Celgene, Sanofi, and UCB outside the submitted work. ES has received research support from AbbVie outside the submitted work. LG has received grant or research support from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, and Galapagos, and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB outside the submitted work. PMM has received consulting or speaker's fees from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB outside the submitted work, and is supported by the UK National Institute for Health Research and University College London Hospitals Biomedical Research Centre. XB has received grant or research support from AbbVie and Novartis, and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB outside the submitted work. JMAG is partially supported by the Instituto de Salud Carlos III. All other authors declare no competing interests., (© 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: To provide an updated review on epidemiology, clinical manifestations, diagnostic assessment, treatment, and prognosis of localized vasculitis, following the 2012 Revised International Chapel Hill Consensus Conference Nomenclature on single-organ vasculitis., Recent Findings: Localized, single-organ vasculitides encompass a group of rare conditions in which there is no evidence of concomitant systemic vasculitis. Most data on this topic derives from case reports and small case series. Although some aspects of these diseases, such as clinical manifestations and histologic findings, have already been extensively investigated, there is still a lack of robust data concerning the pathogenesis, epidemiology, and treatment. Localized vasculitides may have a wide range of clinical features depending on the organ affected. The inflammatory process may have a multifocal/diffuse or unifocal distribution. Diagnosis is usually based on histopathology findings and exclusion of systemic vasculitis, which may frequently pose a challenge. Further research on treatment is warranted.

Objectives: To describe our experience with a coronavirus disease 2019 (COVID-19) outbreak within a large rheumatology department early in the pandemic. Methods: Symptomatic and asymptomatic healthcare workers (HCWs) had a naso-oropharyngeal swab for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were followed clinically. Reverse transcription polymerase-chain reaction (RT-PCR) was repeated to document cure, and serological response was assessed. Patients with risk contacts within the department in the 14 days preceding the outbreak were screened for COVID-19 symptoms. Results: 14/34 HCWs (41%; 40 ± 14 years, 71% female) tested positive for SARS-CoV-2, and 11/34 (32%) developed symptoms but were RT-PCR-negative. Half of RT-PCR-positive HCWs did not report fever, cough, or dyspnea before testing, which were absent in 3/14 cases (21%). Mild disease prevailed (79%), but 3 HCWs had moderate disease requiring further assessment, which excluded severe complications. Nevertheless, symptom duration (28 ± 18 days), viral shedding (31 ± 10 days post-symptom onset, range 15-51), and work absence (29 ± 28 days) were prolonged. 13/14 (93%) of RT-PCR-positive and none of the RT-PCR-negative HCWs had a positive humoral response Higher IgG indexes were observed in individuals over 50 years of age (14.5 ± 7.7 vs. 5.0 ± 4.4, p = 0.012). Of 617 rheumatic patients, 8 (1.3%) developed COVID-19 symptoms (1/8 hospitalization, 8/8 complete recovery), following a consultation/procedure with an asymptomatic (7/8) or mildly symptomatic (1/8) HCW. Conclusions: A COVID-19 outbreak can occur among HCWs and rheumatic patients, swiftly spreading over the presymptomatic stage. Mild disease without typical symptoms should be recognized and may evolve with delayed viral shedding, prolonged recovery, and adequate immune response in most individuals., (Copyright © 2020 Romão, Oliveira-Ramos, Cruz-Machado, Martins, Barreira, Silva-Dinis, Mendonça-Galaio, Proença, Cristino, Sacadura-Leite, Khmelinskii, Romeu, Fonseca and the CHULN Rheumatology Department.)

Inhaled corticosteroids are generally considered safe and do not usually lead to systemic adverse events since their plasma concentrations are low due to hepatic metabolism by the cytochrome P450 3A4. However, when associated with inhibitors of this cytochrome, such as ritonavir, they may lead to iatrogenic Cushing syndrome by the systemic accumulation of corticosteroids and consequent suppression of the hypothalamic-pituitary-adrenal axis. We present a case of iatrogenic Cushing syndrome complicated by multifocal osteonecrosis in a patient with HIV infection on antiretroviral therapy with protease inhibitors boosted with ritonavir, after the association of inhaled fluticasone. This clinical case highlights a relevant interaction between corticosteroids and inhibitors of the cytochrome P450 and the severe consequences that may occur., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development., Results: A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet's disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported., Conclusions: Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.

Objective: To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017., Methods: Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models., Results: The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire-Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months., Conclusion: In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

Imaging has a central role in the diagnosis, management, and follow-up of patients with axial spondyloarthritis (axSpA). For the early diagnosis of axSpA, magnetic resonance imaging is of utmost relevance. While no novel imaging techniques were developed during the past decade, improvements to the existing modalities have been introduced. This report provides an overview of the applications and limitations of the existing imaging modalities.

Introduction: Infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic diseases and the management of infectious complications in patients under biological therapies deserves particular attention., Objective: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies., Methods: A search in PubMed (until 10 November 2014) and EMBASE (until 20 December 2014) databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedicated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey., Results: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the management of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections., Conclusion: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists.