Idiopathic inflammatory myopathies: one year in review 2023.

Idiopathic inflammatory myopathies are a group of rare, autoimmune, diseases typically involving striate muscle and also variously affecting several other systems or organs, such as joints, skin, lungs, heart and gastrointestinal tract. IIM are mainly characterised by subacute onset and chronic course and are burdened by significant morbidity and mortality. Despite the rarity of these conditions, several efforts have been undertaken in the last years to better understand their pathogenesis, as well as to achieve a more precise classification and to define the optimal therapeutic approach. The aim of this review is to provide an up-to-date digest of the most relevant studies published on this topic over the last year.

Cancer-associated myositis before and after the COVID-19 pandemic onset: a changing trend.

OBJECTIVES: During the COVID-19 pandemic, there was a significant impact on the management of non-COVID-19 related diseases, potentially increasing the incidence of paraneoplastic syndromes such as cancer-associated myositis (CAM).The aim of this study is to determine the incidence of CAM in our cohort before and after the COVID-19 pandemic onset. METHODS: We included patients with idiopathic inflammatory myopathy (IIM), diagnosed between June 2016 and June 2023. The patients were divided into two groups according to the date of IIM diagnosis. RESULTS: We included 132 patients; 65.1% (n=86) were diagnosed prior to and 34.9% (n=46) after the COVID-19 pandemic. The most common IIM was dermatomyositis (DM) before and after the COVID-19 pandemic onset (p=0.750). The most frequent myositis-specific antibody (MSA) before the COVID-19 pandemic was anti-Mi2 (15.1%). After the COVID-19 pandemic onset, anti-TIF1γ was the most common MSA (21.7%), with a significantly higher relative prevalence (p=0.006). The incidence of CAM was significantly higher after the COVID-19 pandemic onset (11 vs. 3 new cases, p<0.002). Patients with CAM more frequently had anti-TIF1γ-positivity (p<0.001) and a diagnosis after the pandemic (p=0.001) than non-CAM-IIM patients. No significant differences were found regarding vaccination status or previous COVID-19 infection in CAM and non-CAM-IIM patients. Diagnosis after the COVID-19 pandemic was an independent predictor of CAM among IIM patients (OR 0.012, 95% CI 0.000-0.400, p=0.013), regardless of age, sex or previous COVID-19 infection. CONCLUSIONS: There was a significant increase in the incidence of CAM after the COVID-19 pandemic. IIM diagnosis after the COVID-19 pandemic was an independent predictor of CAM.

Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Idiopathic inflammatory myopathies: one year in review 2022.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of disorders in which chronic inflammation of the skeletal muscle, leading to muscle weakness, is a common feature. Different phenotypes have been identified within the IIM spectrum based on extra-muscular manifestations, immunology, muscle histology, responsiveness to therapy, and prognosis. The pathogenesis, classification, treatment, and prognosis of the different IIM subtypes are subject to active discussion and research. This review highlights the most relevant literature published on this topic over the last year.

The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability.

PURPOSE: To assess the relationship between adherence to the Mediterranean Diet (MD) /individual Dietary Inflammatory Index (DII) and disease activity, disease impact, and functional status in Rheumatoid Arthritis (RA) patients. METHODS: RA patients followed at a hospital in Lisbon, Portugal, were recruited. DII was calculated using dietary intake data collected with a food frequency questionnaire (FFQ). Adherence to the MD was obtained using the 14-item Mediterranean Diet assessment tool. Disease Activity Score of 28 Joints (DAS28) and the DAS28 calculated with C-Reactive Protein (DAS28-CRP) were used to assess disease activity. Impact of disease and functional status were evaluated using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Health Assessment Questionnaire (HAQ), respectively. RESULTS: 120 patients (73.3% female, 61.8 ± 10.1 years of age) were included. Patients with higher adherence to the MD had significantly lower DAS28-CRP (median 3.27(2.37) vs 2.77(1.49), p = 0.030), RAID (median 5.65(2.38) vs 3.51(4.51), p = 0.032) and HAQ (median 1.00(0.56) vs 0.56(1.03), p = 0.013) scores. Higher adherence to the MD reduced the odds of having a higher DAS28 by 70% (OR = 0.303, 95%CI = (0.261, 0.347), p = 0.003). Lower adherence to MD was associated with higher DAS28-CRP (ß = - 0.164, p = 0.001), higher RAID (ß = - 0.311, p < 0.0001), and higher HAQ scores (ß = - 0.089, p = 0.001), irrespective of age, gender, BMI and pharmacological therapy. Mean DII of our cohort was not significantly different from the Portuguese population (0.00 ± 0.17 vs - 0.10 ± 1.46, p = 0.578). No associations between macronutrient intake or DII and RA outcomes were found. CONCLUSIONS: Higher adherence to the MD was associated with lower disease activity, lower impact of disease, and lower functional disability in RA patients.

Hoarseness as the presentation of immunoglobulin G4-related disease with vocal cord and mediastinal infiltration.

Immunoglobulin G4-related disease is a rare fibroinflammatory infiltrative condition with heterogeneous clinical manifestations. We present the case of a 64-year-old man that presented with hoarseness due to vocal cord involvement, a particularly rare manifestation. A large mediastinal mass compressing thoracic large vessels was also identified. The patient was initially treated with glucocorticoids but had relapses during glucocorticoid tapering. Rituximab was started after a careful pre-treatment evaluation of the infectious risk and treatment of comorbidities.

Capillary leak syndrome in a patient with cancer-associated anti-transcriptional intermediary factor 1γ dermatomyositis treated with rituximab.

Capillary leak syndrome (CLS) is a rare condition characterised by increased capillary permeability, with subsequent hypoalbuminemia and hypotension, leading to an increased risk of shock and death. We present the case of a patient with anti-transcriptional intermediary factor 1γ dermatomyositis that developed CLS one week after starting treatment with rituximab and prophylactic co-trimoxazole. The patient was admitted to the Intensive Care Unit (ICU), recovered after treatment with intravenous immunoglobulin, albumin, and Ringer lactate, but died a month after the discharge due to a poorly differentiated hepatocarcinoma diagnosed in the ICU.

Rheumatology residency in a European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases centre: opportunities and challenges.

Rheumatology is a growing medical speciality with many attractive points to young doctors. Residency is a demanding period of a physician's life, and choosing the right hospital for one's residency may not be easy. We report on our personal experience as Rheumatology residents in European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN-ReCONNET) centres.

Localized Forms of Vasculitis.

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.

Reactive arthritis as a rare complication of intravesical bacillus Calmette-Guérin treatment: Report of two cases.

Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is recommended for non-muscle-invasive bladder cancer after transurethral resection. BCG-associated musculoskeletal adverse events are rare. We report two cases of BCG reactive arthritis that were unusually severe and refractory. These describe two male patients who presented with polyarthritis after BCG exposure. Ultrasonography-guided glucocorticoid injections, high-dose systemic glucocorticoids and the institution of sulfasalazine were required for achievement of remission. Bacillus Calmette-Guérin reactive arthritis can present as polyarthritis of small and medium joints or as mono-oligoarthritis of asymmetrical ankles and knees, frequently associated with tenosynovitis and enthesitis. The mechanism by which BCG promotes arthralgia and arthritis is poorly understood. The most well-accepted theory is that the BCG antigens migrate to different peripheral tissues, including the joints. There is also a lack of knowledge regarding risk factors, with possible genetic factors playing a role. As the two presented cases show, BCG-induced reactive arthritis should be considered in the differential diagnosis of arthritis and refractory tenosynovitis in BCG-exposed patients.

Systematic literature review to inform the Portuguese recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases.

OBJECTIVE: To perform a systematic literature review (SLR) aimed at evaluating the efficacy and safety of pharmacological and non-pharmacological treatments for Raynaud's phenomenon (RP) and digital ulcers (DU) in patients with systemic sclerosis (SSc) and other connective tissue diseases (CTD), in order to inform the Portuguese recommendations for managing RP and DU in these patients. METHODS: A SLR was conducted until May 2022 to identify studies assessing the efficacy and safety of pharmacological and non-pharmacological interventions for RP and DU in SSc and other CTD. Eligible study designs included randomized controlled trials (RCTs), controlled clinical trials, and their extensions for assessing efficacy and safety of interventions. Observational studies with a comparator were included for evaluating the efficacy and safety of non-pharmacological interventions and safety of pharmacological interventions. The risk of bias of each study was assessed using standard tools. RESULTS: Out of 71 publications meeting the inclusion criteria, 59 evaluated pharmacological and 12 non-pharmacological interventions. We found moderate quality evidence supporting the efficacy of calcium channel blockers, phosphodiesterase-5 inhibitors, and intravenous prostacyclin analogues in reducing RP frequency, severity, and duration. Intravenous iloprost had a small to moderate effect size in improving DU healing. Phosphodiesterase-5 inhibitors were effective in reducing total DU count, new DU occurrence, and enhancing DU healing. Bosentan effectively prevented new DU in SSc patients. No new safety concerns were associated with these treatments. The studies on non-pharmacological interventions were, in general, of low quality, and had a small sample size. Warming measures decreased frequency and duration of RP attacks; laser therapy improved RP-related outcomes; local oxygen-ozone therapy improved RP outcomes as an add-on therapy; bone marrow mononuclear cell implantation improved DU-associated pain; periarterial sympathectomy and vascular bypass reduced DU number and finger amputation risk. CONCLUSION: The available evidence supports the efficacy and safety of pharmacological interventions, namely nifedipine, sildenafil, iloprost, and bosentan in treating RP and DU in patients with SSc and other CTD. Scarce and low-quality evidence does support the use of some non-pharmacological interventions but with only a modest effect size. This SLR underscores the limited availability of high-quality evidence for determining the optimal treatment.

Anxiety and depression in patients with giant cell arteritis.

Objectives: To compare the prevalence of anxiety and depression in patients with GCA with that in the general population, using the Hospital Anxiety and Depression Scale (HADS), and to identify independent predictors of these psychiatric manifestations in patients with GCA. Methods: We conducted a cross-sectional study including all patients diagnosed with GCA followed during 1 year in a vasculitis outpatient clinic. The HADS and 36-item Short Form (SF-36) questionnaires were prospectively collected. Patients' HADS results were compared with an age- and gender-matched control group. HADS anxiety (HADS-A) and HADS depression (HADS-D) scores between 8 and 10 defined possible anxiety and depression and ≥11 defined probable anxiety and depression, respectively. Results: We included 72 patients and 288 controls. Compared with controls, patients with GCA had a statistically significant higher prevalence of HADS-A ≥8 (48.6% vs 26.4%), HADS-A ≥11 (30.6% vs 12.2%) and HADS-D ≥11 (33.3% vs 18.1%). GCA was an independent predictor of HADS-A ≥8 [odds ratio (OR) 3.3 (95% CI 1.9, 5.9)], HADS-A ≥11 [OR 3.8 (95% CI 2.0, 7.4)] and HADS-D ≥11 [OR 2.6 (95% CI 1.4, 4.7)]. Among patients with GCA, a negative correlation was observed between HADS-A/D and SF-36 mental health scores (r = -0.780 and r = -0.742, respectively). Glucocorticoid therapy was a predictor of HADS-A ≥8 [OR 10.4 (95% CI 1.2, 94.2)] and older age of HADS-D ≥8 [OR 1.2 (95% CI 1.1, 1.3)] and HADS-D ≥11 [OR 1.1 (95% CI 1.0, 1.2)]. Conclusions: Compared with the general population, patients with GCA have a higher prevalence of anxiety and depression and GCA is an independent predictor of these symptoms. Glucocorticoid treatment and older age are predictors of anxiety and depression, respectively, in patients with GCA.

Portuguese Recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases.

OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological and pharmacological management of Raynaud's phenomenon (RP) and digital ulcers (DUs) in patients with systemic sclerosis and other immune-mediated connective tissue diseases (CTDs). METHODS: A task force comprising 21 rheumatologists, two surgeons (vascular and plastic), two nurses, and one patient representative was established. Following a systematic literature review performed to inform the recommendations, statements were formulated and discussed during two meetings (one online and one in-person). Levels of evidence, grades of recommendation (GoR), and level of agreement (LoA) were determined. RESULTS: Five overarching principles and 13 recommendations were developed. GoR ranged from A to D. The mean ± standard difference (SD) LoA with the overarching principles and recommendations ranged from 7.8±2.1 to 9.8±0.4. Briefly, the management of RP and DUs in patients with CTDs should be coordinated by a multidisciplinary team and based on shared decisions with patients. Nifedipine should be used as first-line therapy for RP and/or DUs. Sildenafil, tadalafil, and/or iloprost IV are second-line options for severe and/or refractory patients with RP and/or DUs. Sildenafil, tadalafil and/or Iloprost IV, should be prescribed for healing and prevention (also including bosentan) of DUs. In patients with RP and/or DUs, non-pharmacological interventions might be considered as add-ons, but there is limited quality and quantity of scientific evidence supporting their use. CONCLUSIONS: These recommendations will inform rheumatologists, specialist nurses, other healthcare professionals, and patients about a comprehensive and personalized management of RP and DUs. A research agenda was developed to address unmet needs, particularly for non-pharmacologic interventions.