Impaired physical function in patients with idiopathic inflammatory myopathies: results from the multicentre COVAD patient-reported e-survey.

OBJECTIVES: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs. METHODS: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease. RESULTS: 1057 IIM patients, 3635 non-IIM AIRD patients, and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs (36.3 [95% confidence interval (CI) 35.5-37.1] vs 41.3 [95%CI 40.2-42.5] vs 46.2 [95%CI 45.8-46.6], P < 0.001), irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis. CONCLUSION: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

Presence and Implications of Anti-Angiotensin Converting Enzyme-2 Immunoglobulin M Antibodies in Anti-Melanoma-Differentiation-Associated 5 Dermatomyositis.

OBJECTIVE: Patients with anti-melanoma-differentiation-associated 5 (anti-MDA5)-positive dermatomyositis (DM) share several striking similarities to patients with SARS-CoV-2. Our objective was to assess the prevalence of anti-angiotensin converting enzyme-2 (ACE2) immunoglobulin M (IgM) antibodies, found in patients with severe SARS-CoV-2, in two independent anti-MDA5-positive DM cohorts. METHODS: Anti-ACE2 IgM antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) in two anti-MDA5-positive DM cohorts: a predominantly outpatient North American cohort (n = 52) and a Japanese cohort enriched for new-onset disease (n = 32). Additionally, 118 patients with SARS-CoV-2 with a spectrum of clinical severity were tested for anti-MDA5 antibodies by ELISA. RESULTS: Five of fifty-two (9.6%) North American patients and five of thirty-two (15%) Japanese patients were positive for anti-ACE2 IgM. In the North American cohort, all five patients with anti-ACE2 IgM antibodies had proximal muscle weakness, had interstitial lung disease, were significantly more likely to receive pulse dose methylprednisolone (80% vs 30%, P = 0.043), and had worse forced vital capacity (median 59% predicted vs 78%, P = 0.056) compared with the anti-ACE2-IgM-negative group. In the Japanese cohort, all five anti-ACE2-IgM-positive patients also required pulse dose methylprednisolone, and three of five (60%) patients died. Japanese patients with anti-ACE2 IgM had significantly worse oxygenation, as defined by a lower partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (233 vs 390, P = 0.021), and a higher alveolar-arterial oxygenation gradient (91 vs 23 mm Hg, P = 0.024) than the IgM-negative group. CONCLUSION: We describe anti-ACE2 IgM autoantibodies in two independent cohorts with anti-MDA5-positive DM. These autoantibodies may be biomarkers for severe disease and provide insight into disease pathogenesis.

Refractory Longitudinally Extensive Transverse Myelitis after Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in a Japanese Man.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and administered worldwide. There have been reports of neurological adverse events following immunization (AEFIs). We herein report a case of refractory longitudinally extensive transverse myelitis in a 75-year-old Japanese man following the first dose of the BNT162b2 vaccine. The patient developed total sensory loss below the umbilicus and complete paralysis in both legs. Although he was treated with steroid therapy and plasma exchange, his recovery was limited, and severe sequelae remained. Further studies, including large epidemiological studies, are required to understand the association between SARS-CoV-2 vaccines and neurological AEFI.

Detection of cytokine storm in patients with achalasia using ELISA.

Esophageal achalasia is characterized by abnormal peristaltic movements of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). However, its etiology remains unknown. In our previous study, it was shown that in the LES of patients with achalasia, hsv1-miR-H1 was overexpressed, ATG16L1 expression was downregulated and interleukin (IL)-1ß levels were upregulated. However, systemic features were not evaluated. Herein, the plasma cytokine levels in patients with achalasia were determined. Plasma was collected from patients at Nagasaki University Hospital between February 2013 and March 2016, both before and after peroral endoscopic myotomy (POEM). Cytokine analysis was performed using plasma collected from 10 healthy individuals (control group) and 12 patients with achalasia using the Bio-Plex Pro™ Human Cytokine 27-plex assay kit. The levels of IL-17, IL-1ß, C-C motif chemokine ligand 2, IL-4, IL-5, IL-1ra, IL-7, IL-12, interferon-γ, IL-2, fibroblast growth factor-2, colony-stimulating factor (CSF)2 and CSF3 were significantly higher in patients with achalasia compared with the control subjects. However, the levels did not differ between plasma samples collected before and after POEM. Thus, the occurrence of a cytokine storm was confirmed in the patients with achalasia.