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Ana Teresa Melo,1,2,* Eduardo Dourado,1,2,* Raquel Campanilho-Marques,1,2,* Matilde Bandeira,1,2 Sofia C Barreira,1,2 José Costa,3 Rita Pimenta,4 Sofia Antunes-Duarte,4 Inês Cordeiro,1,2 João E Fonseca1,2 1Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 2Rheumatology Investigation Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 3Physical Medicine and Rehabilitation Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 4Dermatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal*These authors contributed equally to this workCorrespondence: Ana Teresa Melo, Serviço de Reumatologia, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, EPE, R. Prof. Egas Moniz, Lisboa, 1700, Portugal, Tel +351 217805139, Email anateresamelo@campus.ul.ptBackground: Idiopathic inflammatory myopathies (IIM) are a rare heterogeneous group of diseases characterised by chronic skeletal muscle inflammation, but other organs are also frequently involved. IMM represent a diagnostic challenge and a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients.Objective: To describe the general functioning of our multidisciplinary myositis clinic, highlighting the benefits of multidisciplinary team management in patients with confirmed or suspected IIM and to characterise our clinical experience.Methods: Description of the organization of a dedicated multidisciplinary myositis outpatient clinic, supported by IMM specific electronic assessment tools and protocols based on our Portuguese Register - Reuma.pt. In addition, an overview of our activity between 2017 and 2022 is provided.Results: An IIM multidisciplinary care clinic, based on a close collaboration between Rheumatologists, Dermatologists and Physiatrist is detailed in this paper. One hundred and eighty-five patients were assessed in our myositis clinic; 138 (75%) of those were female, with a median age of 58 [45– 70] years. At the last appointment, 130 patients had a confirmed IIM diagnosis, and the mean disease duration was 4 [2– 6] years. The most frequent diagnosis was dermatomyositis (n = 34, 26.2%), followed by antisynthetase syndrome (n = 27, 20.8%) and clinically amyopathic/paucimyopathic dermatomyositis (n = 18, 13.8%). Twenty-four patients (18.5%) were on monotherapy and 94 (72.3%) were on combination therapy.Conclusion: A multidisciplinary approach is important to ensure the correct diagnosis and follow-up of these patients. A myositis clinic, with a standardised practice at a tertiary hospital level, contributes to a standardization of care and opens research opportunities.Keywords: inflammatory myopathies, rheumatology, dermatology, rehabilitation medicine, multidisciplinary clinic

Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 ± 2.86 U/mL) compared to controls (11.85 ± 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = −0.496, p = 0.007), and higher triglyceride levels (r = 0.421, p = 0.020) and TC/HDL and LDL/HDL ratios (r = 0.612, p < 0.001 and r = 0.437, p = 0.023, respectively). Patients with psoriasis have higher ACE activity levels, independent of ACE genotype. Moreover, disease activity correlated with cardiovascular risk. This could support the eventual role of ACE as a possible biomarker for disease severity and cardiovascular risk in psoriasis patients.

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

SARS-CoV-2 infection can present in different clinical forms, most commonly as bilateral pneumonia, but also with pericardial/myocardial involvement. Cardiac involvement in COVID-19 is associated with worse outcomes. The authors report a case of myopericarditis as the primary manifestation of SARS-CoV-2 infection in a 20-year-old male patient with no known cardiovascular (CV) disorders or risk factors. The patient presented with pleuritic chest pain and high fever, with no respiratory symptoms. Electrocardiogram (ECG) and echocardiogram changes were consistent with pericarditis; concomitant elevation of cardiac enzymes revealed myocardial involvement. The patient had a slow but favourable evolution with no apparent impact on cardiac function. Other causes of myopericarditis were excluded and SARS-CoV-2 admitted as the most likely aetiological agent. This case highlights possible cardiac involvement in SARS-CoV-2 infection with little or no pulmonary disease in a young healthy patient. Such systemic and potentially troublesome manifestations of COVID-19 are increasingly being described.Acute myopericarditis is a possible manifestation of SARS-CoV-2 infection.SARS-CoV-2 cardiac involvement may occur both in older and in younger previously healthy subjects, and could be more frequent than expected.Further investigation should address the prevalence of myocardium and pericardium involvement in COVID-19 patients, as well as its complications, sequelae and prognostic value for both older and young patients.

In order to identify risk factors for SARS-CoV-2 infection as well as for severe/critical COVID-19 in rheumatic and musculoskeletal diseases (RMDs) patients, we conducted a multicentre observational nationwide study of adult patients prospectively-followed in the Rheumatic Diseases Portuguese Register – Reuma.pt – during the first 6 months of the pandemic. We further evaluated the development of IgG antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in patients with RMDs. We used multivariate logistic regression to compare patients with COVID-19 (COVID-19+) with those who did not develop the disease (COVID-19-) and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. COVID-19+ patients were asked to collect a blood sample for IgG testing ≥ 3 months after infection and results were compared with age-, sex- and sampling date-matched controls. Overall, 179 cases of COVID-19 were registered in Reuma.pt in the period of interest (median age 55 (IQR 20); 76.5% females) in a total of 6404 registered appointments. We found that patients treated with TNF inhibitors had reduced odds of infection (OR=0.16, 95%CI 0.10-0.26, p

BackgroundVitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways.MethodsThis study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed.ResultsThe results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.042). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%).ConclusionThis study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registrationNCT04370808

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021, Purpose of review: In recent years, the spectrum of neurological manifestations of antiphospholipid syndrome (APS) has been growing. We provide a critical review of the literature with special emphasis on presentation, proposed mechanisms of disease, and treatment of neurological involvement in APS. Recent findings: Although stroke is the most common cause of neurological manifestations in patients with APS, other neurological disorders have been increasingly associated with the disease, including cognitive dysfunction, headache, and epilepsy. Direct oral anticoagulants have failed to show non-inferiority compared to vitamin K antagonists for the prevention of major thrombotic events. Antiphospholipid antibodies are often found in patients with acute COVID-19 but clear evidence supporting an association between these antibodies and the risk of thrombotic events, including stroke and cerebral venous thrombosis, is still lacking. APS patients may present with several distinct neurological manifestations. New criteria will facilitate the classification of patients presenting with increasingly recognized non-criteria neurological manifestations.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases., This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.

We aimed to investigate the clinical off-label use of mycophenolate mofetil (MMF), including its safety and efficacy in patients with rare and complex rheumatic connective tissue diseases (rCTDs).A survey was distributed across experts from ERN-ReCONNET reference centres in order to assess the experience with MMF off-label use. Patient-level data of patients with rCTDs under treatment with MMF was also collected for analysis of safety and efficacy.Twelve experts from eleven centres distributed throughout Europe (7 countries) answered the survey. The experience was concordant in that, despite of its off-label use, experts reported opting frequently for this therapeutic alternative with robust confidence on its efficacy and safety. The analysis of 108 patients with rCTDs under MMF revealed a good safety profile, as well as good clinical outcomes, especially for systemic lupus erythematosus and idiopathic inflammatory myopathies. The presence of interstitial lung disease was, as expected, associated with a worse clinical outcome despite use of MMF.MMF is widely used in reference centres for rCTDs. Its safety profile and efficacy seem to be recognised by experts and demonstrated with patient-level analysis. While selected rCTDs will likely remain an off-label indication for MMF, robust data seem to support this therapy as an appropriate alternative for safely and effectively treating many manifestations of rCTDs.