Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study.

OBJECTIVES: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). METHODS: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. RESULTS: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. CONCLUSION: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.

COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey.

OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7). CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.

COVID-19 vaccination in autoimmune disease (COVAD) survey protocol.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators.

Sporadic inclusion body myositis: Diagnostic value of p62 immunostaining.

BACKGROUND AND OBJECTIVES: Sporadic inclusion body myositis (sIBM) diagnosis is frequently delayed or confused with another class of disorders, and misdiagnosis is common. Sometimes, we have problems diagnosing an sIBM in the early stages or predicting when a PM is going to become an sIBM. In this sense, we believe that p62 immunostaining could help clinicians. CASE REPORT: We report the case of a 61-year-old patient with sIBM who six years earlier had been diagnosed with polymyositis (PM). After muscle biopsies analyses, we showed the natural history of sIBM by p62 expression. RESULTS: When we looked for p62 aggregates retrospectively we could see small dotted p62 aggregates in the muscle fibres of the first muscle biopsy. Six years later, the patient presented with the typical clinical picture of sIBM, also the muscle biopsy was characteristic, with large p62 aggregates. CONCLUSIONS: Probably p62 immunostaining could help to distinguish PM patients that are going to become sIBM, but to date there has been no systematic study to clarify p62 utility in myositis.

BACE-1, PS-1 and sAPPß Levels Are Increased in Plasma from Sporadic Inclusion Body Myositis Patients: Surrogate Biomarkers among Inflammatory Myopathies.

Sporadic inclusion body myositis (sIBM) is a rare disease that is difficult to diagnose. Muscle biopsy provides three prominent pathological findings: inflammation, mitochondrial abnormalities and fibber degeneration, represented by the accumulation of protein depots constituted by ß-amyloid peptide, among others. We aim to perform a screening in plasma of circulating molecules related to the putative etiopathogenesis of sIBM to determine potential surrogate biomarkers for diagnosis. Plasma from 21 sIBM patients and 20 age- and gender-paired healthy controls were collected and stored at -80°C. An additional population of patients with non-sIBM inflammatory myopathies was also included (nine patients with dermatomyositis and five with polymyositis). Circulating levels of inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α), mitochondrial-related molecules (free plasmatic mitochondrial DNA [mtDNA], fibroblast growth factor-21 [FGF-21] and coenzyme-Q10 [CoQ]) and amyloidogenic-related molecules (beta-secretase-1 [BACE-1], presenilin-1 [PS-1], and soluble Aß precursor protein [sAPPß]) were assessed with magnetic bead-based assays, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and high-pressure liquid chromatography (HPLC). Despite remarkable trends toward altered plasmatic expression of inflammatory and mitochondrial molecules (increased IL-6, TNF-α, circulating mtDNA and FGF-21 levels and decreased content in CoQ), only amyloidogenic degenerative markers including BACE-1, PS-1 and sAPPß levels were significantly increased in plasma from sIBM patients compared with controls and other patients with non-sIBM inflammatory myopathies (p < 0.05). Inflammatory, mitochondrial and amyloidogenic degeneration markers are altered in plasma of sIBM patients confirming their etiopathological implication in the disease. Sensitivity and specificity analysis show that BACE-1, PS-1 and sAPPß represent a good predictive noninvasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis.