The idiopathic inflammatory myopathies module of the Rheumatic Diseases Portuguese Register.

AIMS: To characterise the idiopathic inflammatory myopathies (IIM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/myositis) and the patients in its cohort. METHODS: Reuma.pt is a web-based system with standardised patient files gathered in a registry. This was a multicentre open cohort study, including patients registered in Reuma.pt/myositis up to January 2022. RESULTS: Reuma.pt/myositis was designed to record all relevant data in clinical practice and includes disease-specific diagnosis and classification criteria, clinical manifestations, immunological data, and disease activity scores. Two hundred eighty patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years. Patients were classified as having definite (N=57/118, 48.3%), likely (N=23/118, 19.5%), or possible (N=2/118, 1.7%) IIM by 2017 EULAR/ACR criteria. The most common disease subtypes were dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), and myositis in overlap syndromes (N=41/280, 14.6%). The most common symptoms were proximal muscle weakness (N=180/215, 83.7%) and arthralgia (N=127/249, 52.9%), and the most common clinical signs were Gottron's sign (N=75/184, 40.8%) and heliotrope rash (N=101/252, 40.1%). Organ involvement included lung (N=78/230, 33.9%) and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%). Cancer was found in 11/127 patients (8.7%), most commonly breast cancer (N=3/11, 27.3%). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), and mycophenolate mofetil (N=56/280, 20.0%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125). CONCLUSIONS: Reuma.pt/myositis adequately captures the main features of inflammatory myopathies' patients, depicting, in this first report, a heterogeneous population with frequent muscle, joint, skin, and lung involvements.

Rheumatoid arthritis and Hailey-Hailey disease treated with methotrexate.

We report a rare case of long-standing Hailey-Hailey disease in a Caucasian Portuguese 69-year-old woman, recently diagnosed with rheumatoid arthritis. The patient's skin lesions remained active and exudative despite topical and oral treatments with corticosteroids, tetracyclines, antifungals, and oral treatment with azathioprine. After introduction of methotrexate for rheumatoid arthritis treatment, the skin lesions regressed, with significant impact on the patient's quality of life. This case report supports the clinical evidence of methotrexate's potential role in Hailey-Hailey disease treatment.

Ethics and non-evidence based therapies: Portuguese perspective in a global setting.

A contemporary serious lack of scientific knowledge by the general public and many decision-makers is now quite perceptible, both globally and in Portugal. Living in a science-driven technological world filled with scientific illiteracy is dangerous and a path toward disaster. Recent years brought a fairly strong global movement promoting the so-called "alternative therapy" that also affected Portugal. I propose an evidence-based ethics reflection and argumentation, both encompassing the global and the specific Portuguese reality. I debate the specific arguments used in favour of alternative therapies, demonstrating the inherent fallacies of thought, deliberate manipulation of words and concepts, and the dire consequences for global and local health politics by following this line of biased reasoning.

Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.

Pachydermodactyly: the role of ultrasonography, superb microvascular imaging, and elastography in diagnosis.

Pachydermodactyly is a rare and benign superficial fibromatosis characterized by painless and progressive swelling of periarticular soft tissues of the proximal interphalangeal (PIP) joints, most commonly of both hands. There is no tenderness, warmth, morning stiffness, or reduced range of motion associated. Our purpose is to highlight the diagnostic utility of ultrasonography, superb microvascular imaging (SMI), and elastography in pachydermodactyly. We report the case of a 15-year-old adolescent white boy, with a 6-month history of insidious and progressive, asymptomatic swelling of the lateral and dorsal regions of the metacarpophalangeal (MCP), and PIP joints of both hands. Articular ultrasonography showed thickening of the skin around the lateral regions of the PIP and MCP joints, with no synovitis, hydrarthrosis, or muscle, tendon, or bone changes. Strain elastography revealed lower elasticity in the aforementioned skin regions, corresponding to increased tissue hardness due to hyperkeratosis. No SMI or Doppler signals were detected in epidermal or dermal tissues, as well as in tendons, joints, and bone. This case report shows that ultrasonography, SMI, and elastography may play a significant role in the accurate diagnosis of pachydermodactyly and exclusion of alternative conditions. These imaging modalities have no ionizing radiation; they are fast, inexpensive, and performed on site. They do not require usage of contrast agents and thus can eliminate the need of invasive procedures such as skin biopsy. They also contribute to reduce health care costs with unnecessary complementary tests and inappropriate treatment.

Ultrasound registry in Rheumatology: a first step into a foreseeable future.

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Portuguese recommendations for the use of ultrasound in rheumatology.

INTRODUCTION: Ultrasound (US) is a relatively cheap, easily available and reliable method to improve the care of rheumatic patients. However, its use in rheumatology practice is very heterogeneous and needs to be standardized. OBJECTIVES: To develop recommendations for the use of US in rheumatic diseases endorsed by the Portuguese Society of Rheumatology. METHODS: A systematic literature review of the available recommendations on the use of ultrasound in rheumatic diseases was performed and presented in a Portuguese Society of Rheumatology meeting to a subgroup of rheumatologists and rheumatology trainees with special interest in the subject. The most important topics to be addressed were selected and assigned to subgroups for literature review and draft recommendations. Following an iterative process of consensus, the final recommendations were developed, and their level of agreement voted anonymously online. A recommendation was approved when the average level of agreement was ≥ 7.5 in a 10-point Likert scale. RESULTS: Fourteen recommendations were produced regarding nine rheumatology topics: rheumatoid arthritis, spondyloarthritis, connective tissue diseases, polymyalgia rheumatica, vasculitis, crystal-deposition diseases, soft tissue rheumatism, osteoarthritis and ultrasound-guided procedures. CONCLUSION: We developed an up-to-date guidance in the form of recommendations for the use of US in nine different areas of rheumatology. As ultrasound is an important imaging modality with increasing use in the rheumatology setting, and there are frequent technological advances in the ultrasound machines and probes, in parallel with continuous associated research, these recommendations should be regularly updated.

EULAR 'points to consider' for the conduction of workforce requirement studies in rheumatology.

OBJECTIVE: Current methods used for forecasting workforce requirements in rheumatology are disparate, as are the parameters incorporated into workforce projection studies. The objective of these European League Against Rheumatism (EULAR points to consider (PTC) is to guide future workforce studies in adult rheumatology in order to produce valid and reliable manpower estimates. METHODS: The EULAR Standardised Operating Procedures were followed. A multidisciplinary task force with experts including patients with rheumatic diseases from 11 EULAR countries and the USA was assembled. A systematic literature review (SLR) was conducted to retrieve workforce models in rheumatology and other medical fields. PTC were based on expert opinion informed by the SLR, followed by group discussions with consensus obtained through informal voting. The level of agreement with the PTC was voted anonymously. RESULTS: A total of 10 PTC were formulated. The task force recommends models integrating supply (=workforce available in rheumatology), demand (=health services requested by the population) and need (=health services that are considered appropriate to serve the population). In general, projections of workforce requirements should consider all factors relevant for current and future workload in rheumatology inside and outside of direct patient care. Forecasts of workforce supply should consider demography and attrition of rheumatologists, as well as the effects of new developments in healthcare. Predictions of future need/demand should take demographic, sociocultural and epidemiological development of the population into account. CONCLUSION: These EULAR-endorsed PTC will provide guidance on the methodology and the parameters to be applied in future national and international workforce requirement studies in rheumatology.

Portuguese Recommendations for the use of biological therapies in patients with rheumatoid arthritis- 2016 update.

OBJECTIVE: To update the recommendations for the treatment of Rheumatoid Arthritis (RA) with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 10 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, assessment of activity and RA impact and treatment objective. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Pachydermoperiostosis in an African patient caused by a Chinese/Japanese SLCO2A1 mutation-case report and review of literature.

OBJECTIVES: Pachydermoperiostosis is a rare clinical entity characterized by skin thickening of the forehead, eyelids, and hands, digital clubbing, and periostosis. Two genes have been associated, HPGD and recently SLCO2A1. We present a detailed clinical and genetic description of an African pachydermoperiostosis patient with a SLCO2A1 mutation. METHODS: Standard clinical and laboratory evaluation was carried out. Genetic screening was done with PCR followed by direct sequencing. We discuss the clinical features and known mutations of previously reported cases identified through a PubMed literature review. RESULTS: The clinical findings showed special features, including exuberant knee effusions and an extraordinary good response on surgery of the blepharoptosis. We found a splice site mutation in the SLCO2A1 gene in homozygous form: c.940+1G>A. This mutation was previously reported only in 1 Chinese and 3 Japanese cases and was considered as a founder mutation in Japan. Beside our case, only one other patient in the literature carried this mutation in homozygous condition, but with different main clinical symptoms. CONCLUSIONS: Our case demonstrates phenotypic heterogeneity of PDP even between homozygous carriers of the same mutation, suggesting further modifiers. Besides, it shows that this rare SLCO2A1 mutation is not exclusively present in East-Asia, but can occur in various ethnicities, with different origin, thus the incidence is probably underestimated.

Comparison of remission criteria in a tumour necrosis factor inhibitor treated rheumatoid arthritis longitudinal cohort: patient global health is a confounder.

INTRODUCTION: Our objectives were to assess the frequency and sustainability of American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) and Disease Activity Score (DAS)28(4v)-C-reactive protein (CRP) remission 12 months after the initiation of tumour necrosis factor inhibitor (TNFi) therapy in a rheumatoid arthritis (RA) cohort. METHODS: Data were collected of 273 biologic naive RA patients at baseline, then 3, 6 and 12 months post-TNFi therapy. Remission status was calculated using DAS28(4v)-CRP <2.6 and ACR/EULAR Boolean criteria. Response was scored using EULAR criteria. RESULTS: Mean (range) patient age was 59.9 (7.2-85.4) years with disease duration of 13.4 (1.0-52.0) years. Responder status maintained from 3-12 months (86%, 82.4%), laboratory/clinical parameters (erythrocyte sedimentation rate (ESR), CRP, patient global health (PGH), DAS28(4v)-CRP) also showed sustained improvement (P < 0.05). DAS28 remission was reached by 102 subjects at 1 year, 27 patients were in Boolean remission, but 75 missed it from the DAS28 remission group. Patients in remission were younger (P = 0.041) with lower baseline tender joint count (TJC)28 and PGH than those not in remission (P = 0.001, P = 0.047). DAS28 remission patients were older (P = 0.026) with higher 12 months PGH and subsequently higher DAS28 than Boolean remission patients (P < 0.0001). Patients not achieving Boolean remission due to missing one subcriteria most frequently missed PGH ≤1 criteria (79.8%). CONCLUSIONS: Only 10% of this TNFi treated cohort achieved remission according to the new ACR/EULAR criteria, which requires lower disease activity. More stringent criteria may ensure further resolution of disease activity and better longterm radiographic outcome, which supports earlier intervention with biologic therapy in RA.

Localized Pigmented Villonodular Synovitis of the shoulder: a rare presentation of an uncommon pathology.

Pigmented Vilonodular Synovitis is a rare clinical entity characterized as a synovial membrane benign tumour, despite possible aggressive presentation with articular destruction. The localized variant is four times less frequent and the shoulder involvement is uncommon. We present the case of a Caucasian 59 year-old patient, who presented with left shoulder pain, of uncharacteristic quality, with local swelling and marked functional limitation of 1 month duration. Shoulder ultrasonography showed subacromial bursitis. An ultrasound-guided aspiration was performed: synovial fluid was citrine-colored and translucid. One month later, the patient maintained swelling, pain and functional impairment of the left shoulder. New shoulder ultrasound revealed exuberant subacromial bursitis, which was again aspirated using ultrasound guidance. The synovial fluid was haematic, without changes in the cell count or biochemical analysis and cultural exams. We performed an injection with 60 mg of hexacetonide triamcinolone. Two months later there was a relapse, with shoulder ultrasonography once more showing subacromial bursitis with extensive synovial membrane proliferation. Shoulder MRI revealed subacromial bursitis involving the anterior, posterior and medial recesses, with deltoid distension, but without tendinous or intra-articular involvement. In the interior of the bursa hypointense images in T2 were observed, suggesting the diagnosis of Pigmented Vilonodular Synovitis. The patient had surgical bursectomy with success and without complications. The histological exam of the operatory piece confirmed the imaging diagnosis. Pigmented Vilonodular Synovitis is uncommon, rarely affecting the shoulder in a localized variant. It is a diagnosis to be considered in shoulder pain, especially if associated with recurrent subacromial bursitis.

A Sinovite Vilonodular Pigmentada é uma entidade clínica rara caracterizada como um tumor benigno da membrana sinovial, apesar de possível apresentação agressiva com destruição articular. A variante circunscrita é quatro vezes menos frequente e o envolvimento do ombro é incomum. Apresentamos o caso de uma doente de 59 anos de idade, que apresentava omalgia à esquerda, incaracterística, com tumefacção local e limitação funcional de um mês de duração. A ecografia do ombro mostrou bursite subacromial. Foi efectuada uma aspiração ecoguiada: o líquido sinovial era translúcido e de cor citrina. Um mês mais tarde, a doente mantinha tumefacção, dor e incapacidade funcional do ombro esquerdo. Foi efectuada nova ecografia do ombro, que revelou bursite subacromial exuberante, que foi novamente aspirada com apoio ecográfico. O líquido sinovial era hemático, sem alterações nos exames culturais e citoquímico. Efectuou-se injecção ecoguiada na bursa com 80 mg de hexacetonido de triamcinolona. Dois meses mais tarde houverecorrência de sintomas e a ecografia mostrou uma vez mais bursite subacromial com proliferação sinovial extensa. A RMN do ombro revelou bursite subacromial envolvendo os recessos anteriores, posterior e interno, com distensão do deltóide, mas sem envolvimento tendinoso ou intra-articular. No interior da bursa observaram-se imagens hipointensas em T2, sugerindo o diagnóstico de Sinovite Vilonodular Pigmentada. A doente foi sujeita a bursectomia cirúrgica, com sucesso e sem complicações. O exame histológico da peça operatória confirmou o diagnóstico imagiológico. A Sinovite Vilonodular Pigmentada é incomum, raramente afectando o ombro na variante circunscrita. É um diagnóstico a ser considerado na omalgia, especialmente se associado a bursite subacromial recorrente.

BAFF and TACI gene expression are increased in patients with untreated very early rheumatoid arthritis.

OBJECTIVE: B cells play important roles in rheumatoid arthritis (RA). Given the beneficial effect of B cell depletion therapy in RA as well as the observed alterations in B cell subpopulations in this disease, we evaluated whether changes in the expression of genes related to B cell survival and activation were already present in patients with untreated very early RA (VERA; < 6 weeks of disease duration). METHODS: The expression of a group of B cell-related activation and survival genes was quantified in peripheral blood mononuclear cells from patients with VERA by real-time PCR and compared with untreated early RA (< 1 year), established treated RA, and other untreated early arthritis conditions. Serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) was quantified by ELISA. RESULTS: BAFF gene expression and serum levels were highest in patients with VERA. The expression of BAFF receptor (BAFF-R) increased with disease progression, while transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) was elevated since the first weeks of RA onset. Paired box 5 gene expression was also increased at all RA stages. Chemokine (C-X-C motif) receptor 5 was elevated only in established RA. No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression. CONCLUSION: Disturbances in the expression of B cell-related activation and survival genes, particularly BAFF and TACI, occur from the onset of RA and precede changes in BAFF-R. These alterations can lead to the development of autoreactive B cells from the first weeks of RA onset.