Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Inflammatory myopathies: shedding light on promising agents and combination therapies in clinical trials.

INTRODUCTION: Due to new insights into the pathogenesis of inflammatory myopathies - in short myositis - and the urgent need for new treatment options in patients who are refractory to standard therapy, multiple novel drugs have been developed and studied in clinical trials. In light of this exciting development, a critical evaluation of the present data is necessary in order to identify the best pathway to future treatment of inflammatory myopathies. AREAS COVERED: This review focuses on the current evidence from clinical trials in myositis and encompasses dermatomyositis, polymyositis, necrotizing myopathy, antisynthetase-syndrome, overlap myositis, and inclusion body myositis. The results of studies on new therapeutic agents are summarized, in particular larger cohort studies and randomized trials from recent years. When such data were not available, earlier and smaller representative studies were included instead. EXPERT OPINION: Current studies in most myositis subtypes have shown positive effects of novel biologicals such as abatacept, sifalimumab, JAK-Inhibitors as well as known agents such as rituximab, but further studies are needed to confirm these observations. In inclusion body myositis, the eagerly awaited recent therapeutic trials have missed their primary endpoints, except for the phase 2 study with rapamycin, which has demonstrated significant improvements in secondary endpoints. Future trials will also need to focus on combination therapies of multiple immunomodulatory agents.

Dyspnea, Elevated Jugular Venous Pulse, and Lower Extremity Edema in the Setting of Interstitial Lung Disease in a Patient Who Has Undergone Liver and Kidney Transplantation.

CASE PRESENTATION: A 64-year-old man with a past medical history of alcoholic cirrhosis with resultant hepatorenal syndrome requiring kidney and liver transplantation 10 years previously sought treatment at the ED with progressive lower-extremity edema and dyspnea. After noting worsening shortness of breath and cough as an outpatient, he had been referred to a pulmonary clinic and was undergoing a workup for interstitial lung disease (ILD). He had been started on prednisone 40 mg/d after a lung biopsy 4 months before admission. He was also receiving chronic immunosuppression with tacrolimus and mycophenolate mofetil. He had noted worsening of edema since starting prednisone.

MR imaging findings of musculoskeletal involvement in microscopic polyangiitis: a comparison with inflammatory myopathy.

OBJECTIVE: The purpose of this study was to evaluate the importance of MR imaging findings of musculoskeletal involvement of the lower limbs in diagnosing microscopic polyangiitis (MPA) vs polymyositis (PM) or dermatomyositis (DM). MATERIALS AND METHODS: This study included 13 patients diagnosed with MPA clinically and through histologically, and 38 diagnosed with PM/DM, who underwent MR imaging of the lower limbs prior to treatment. Axial and coronal short tau inversion recovery (STIR) images were reviewed retrospectively. RESULTS: The sites affected by MPA were the lower legs in six (46%) patients and the thighs in seven (54%). Intramuscular hyperintensity and fascial hyperintensity were observed in all cases of MPA (100%). Fascial hyperintensity was more frequently encountered in MPA than in PM/DM (100% vs. 45%, p < 0.01). As the predominantly involved sites, the fascial regions were more frequently affected by MPA than by PM/DM (77% vs. 18%, p < 0.01). Diffuse subcutaneous fat hyperintensity was more frequently observed in MPA than in PM/DM (100% vs. 16%, p < 0.01). However, no significant differences in intramuscular hyperintensity (100% vs. 97%, p = 0.745) and subcutaneous fat hyperintensity (54% vs. 50%, p = 0.533) were found between MPA and PM/DM. CONCLUSION: Intramuscular hyperintensity and fascial hyperintensity have always been observed in MPA, and the predominantly affected sites were usually the fascial regions. Compared with PM/DM, fascial hyperintensity and diffuse subcutaneous fat hyperintensity were more frequent in MPA.

Sex Dimorphism in Muscle Damage-induced Inflammation.

INTRODUCTION: The purpose of this study was to determine the effect of resistance exercise (RE)-induced hormonal changes on intramuscular cytokine gene expression after muscle damage in untrained men and women. METHODS: Men (n = 8, 22 ± 3 yr) and women (n = 8, 19 ± 1 yr) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either an upper body RE bout (EX) or a time-matched period (CON). Muscle samples (vastus laterals) were analyzed for mRNA expression of interleukin (IL) 6, IL-10, IL-15, TNFA, TGFB, CCL2, and CD68 at PRE, 12 h, and 24 h after the session. RESULTS: A significant time-sex-condition interaction was found for TGFB with an increase for EX in men at 12 h from PRE. For EX, TGFB was also greater in men than in women at 12 and 24 h. Significant time-sex and condition-sex interactions were found for IL-10 with an increase for men that was greater than for women at 12 and 24 h. IL-10 was lower in EX than CON for men. A significant time-sex interaction was found for TNFA with an increase for men that was greater than for women at 24 h. A significant time-condition interaction was found for CD68 with an increase at 12 h and decrease at 24 h for EX and CON. CD68 was lower in EX than CON at 12 h. A significant time effect was found for IL6 and CCL2 with an increase at 12 and 24 h. CONCLUSIONS: Results suggest that women seem to have a muted intramuscular cytokine (i.e., IL-10, TNF-α, and TGF-ß) response to muscle damage compared with men.

COVID-19 and Myositis: What We Know So Far.

PURPOSE: Myositis as a rare manifestation of COVID-19 is only recently being reported. This review examines the current literature on COVID-19-induced myositis focusing on etiopathogenesis, clinical presentations, diagnostic practices, and therapeutic challenges with immunosuppression, and the difficulties experienced by rheumatologists in established myositis in the COVID-19 era. RECENT FINDINGS: COVID-19 is associated with a viral myositis attributable to direct myocyte invasion or induction of autoimmunity. COVID-19-induced myositis may be varied in presentation, from typical dermatomyositis to rhabdomyolysis, and a paraspinal affliction with back pain. It may or may not present with acute exponential elevations of enzyme markers such as creatine kinase (CK). Virus-mediated muscle inflammation is attributed to ACE2 (angiotensin-converting enzyme) receptor-mediated direct entry and affliction of muscle fibers, leading on to innate and adaptive immune activation. A greater recognition of the stark similarity between anti-MDA5-positive myositis with COVID-19 has thrown researchers into the alley of exploration - finding common etiopathogenic basis as well as therapeutic strategies. For patients with established myositis, chronic care was disrupted during the pandemic with several logistic challenges and treatment dilemmas leading to high flare rates. Teleconsultation bridged the gap while ushering in an era of patient-led care with the digital transition to tools of remote disease assessment. COVID-19 has brought along greater insight into unique manifestations of COVID-19-related myositis, ranging from direct virus-induced muscle disease to triggered autoimmunity and other etiopathogenic links to explore. A remarkable shift in the means of delivering chronic care has led patients and caregivers worldwide to embrace a virtual shift with teleconsultation and opened doorways to a new era of patient-led care.

Sexual function in patients with idiopathic inflammatory myopathies: a cross-sectional study.

OBJECTIVES: To date, there is almost no information concerning the sexual health of patients with idiopathic inflammatory myopathies (IIM). This cross-sectional study aimed to compare sexual function in patients with IIM to age-/sex-matched healthy controls (HC) and determine the potential impact of clinical features on sexual function. METHODS: In total, 122 women (61 with IIM, 61 age-matched HC) and 22 men (11 with IIM, 11 age-matched HC) aged 18-80 years completed gender-specific selection of 7 well-established and validated questionnaires assessing sexual health and function (Female Sexual Function Index, Brief Index of Sexual Function for Women, Sexual Function Questionnaire, Sexual Quality of Life Questionnaire-Female, International Index of Erectile Function, Male Sexual Health Questionnaire, Sexual Quality of Life Questionnaire-Male). Results were compared between patients and HC and correlated with selected disease-related features. RESULTS: The prevalence of sexual dysfunction in IIM was 59% in women (vs 40% in HC), and 64% (vs 9% in HC) in men. Men and women with IIM reported significantly impaired sexual function compared with sex-/age-matched HC. Decreased sexual function was associated with muscle weakness, disability, physical inactivity, fatigue, depression and decreased quality of life. CONCLUSIONS: Our results suggest that sexual dysfunction is common among IIM patients and more attention should be paid to this aspect of the disease.

A 64-Year-Old Man With Multifocal Infiltrates.

CASE PRESENTATION: A 64-year-old previously healthy man presented with 8 weeks of progressive dyspnea on exertion and cough. Prior to presentation, the patient was able to bicycle > 60 miles per week and work full-time in a home improvement store. He was up-to-date with age-appropriate cancer screening and immunizations, and home medications included famotidine for reflux and nonsteroidal antiinflammatories for osteoarthritis, both as-needed. He had no significant respiratory exposure, aside from previous work as an electrician. His symptoms began in mid-February 2020 amid the coronavirus disease 2019 pandemic, although he had no known exposure to the virus.

Reliability, validity and responsiveness of physical activity monitors in patients with inflammatory myopathy.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) cause proximal muscle weakness, which affects the ability to carry out the activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity and potentially have clinical usefulness in the assessment of IIMs. We examined the psychometric characteristics for PAM outcomes in IIMs. METHODS: Adult IIM patients were prospectively evaluated (at baseline, 3 months and 6 months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/minute, peak 1-minute cadence, and vector magnitude/minute. Validated myositis core set measures (CSMs) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extramuscular disease activity (Ex-muscular global), HAQ-DI (HAQ disability index), muscle enzymes, and patient-reported physical function were evaluated. Test-retest reliability, construct validity, and responsiveness were determined for PAM measures and CSMs, using Pearson correlations and other appropriate analyses. RESULTS: A total of 50 adult IIM patients enrolled [mean (s.d.) age, 53.6 (14.6); 60% female, 94% Caucasian]. PAM measures showed strong test-retest reliability, moderate-to-strong correlations at baseline with MD global (r = -0.37 to -0.48), Pt global (r=-0.43 to -0.61), HAQ-DI (r = -0.47 to -0.59) and MMT (r = 0.37-0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal associations with MD global (r=-0.38 to -0.44), MMT (r = 0.50-0.57), HAQ-DI (r = -0.45 to -0.55) and functional tests (r = 0.30-0.65) were moderate to strong. PAM measures were responsive to MMT improvement ≥10% and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-minute cadence had the largest effect size and standardized response means. CONCLUSION: PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-minute cadence. PAMs are able to provide valid outcome measures for future use in IIM clinical trials.

Predictors, outcome and characteristics of oropharyngeal dysphagia in idiopathic inflammatory myopathy.

INTRODUCTION: Oropharyngeal dysphagia is a clinical hallmark of idiopathic inflammatory myopathy (IIM). This study investigated predictors, outcome, and characteristics of oropharyngeal dysphagia in patients with different types of IIM. METHODS: Flexible endoscopic evaluation of swallowing (FEES) videos of 71 IIM patients were retrospectively analyzed for bolus spillage, penetration, aspiration, and pharyngeal residue. Based on these findings, dysphagia severity was rated. Regression analyses were performed to investigate demographic and disease-specific predictors of dysphagia severity and pneumonia as outcome-relevant complications of dysphagia. A score was developed to rate the quality of the endoscopic white-out as a surrogate marker for pharyngeal muscle weakness with consecutive residue. RESULTS: Our analysis revealed no independent predictors of dysphagia severity. Dysphagia severity, however, was an independent predictor for pneumonia, which occurred in 24% of patients. Pharyngeal residue with risk of postdeglutitive aspiration was the most common dysphagia pattern. Attenuation of the endoscopic white-out was related to residue severity. DISCUSSION: Dysphagia in IIM assessed with FEES is associated with relevant complications, such as aspiration pneumonia, and must be considered independently of peripheral muscle weakness and disease duration. Swallowing impairment mainly presents with pharyngeal residue. The quality of the white-out may serve as a semi-quantitative surrogate marker for pharyngeal contractility.

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals.

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.

Clinical features of anti-synthetase syndrome associated interstitial lung disease: a retrospective cohort in China.

BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD. METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies. RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic's hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05). CONCLUSION: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.

Functioning in adult patients with idiopathic inflammatory myopathy: Exploring the role of environmental factors using focus groups.

OBJECTIVE: Health-related quality of life is impaired in idiopathic inflammatory myopathies. This study aimed to identify the main areas of the health-related quality of life environment domain that are affected in patients with myositis. METHODS: A qualitative study was performed using focus groups and applying the International Classification of Functioning, Disability, and Health. Participants were recruited from a cohort of 323 adult inflammatory myopathy patients consulting at a reference center for idiopathic inflammatory myopathy in Spain, selected by the maximum variation strategy, and placed in focus groups with 5 to 7 patients per group. The number of focus groups required was determined by data saturation. RESULTS: Twenty-five patients distributed in 4 focus groups were interviewed. The verbatim provided 54 categories directly related with environmental factors. Those associated with products or substances for personal consumption (e110), health professionals (e355), health services, systems and policies (e580), products and technology for personal use in daily living (e115), and immediate family (e310) were the ones most frequently reported. CONCLUSION: The results of this study led to identification of several environmental factors that affect the health-related quality of life of patients with myositis. Remedial interventions should be designed to address some of these factors.

Characteristics and outcomes of overlap myositis: a comparative multigroup cohort study in adults from the MyoCite cohort.

Overlap myositis (OM), an important subset of idiopathic inflammatory myopathies (IIM), is being increasingly recognized with wider myositis-specific autoantibody (MSA) testing. We studied the differences in clinical characteristics and long-term outcomes of OM with Dermatomyositis (DM), Polymyositis (PM), anti-synthetase syndrome (ASSD), and Cancer-associated IIM (CAM). Data from the MyoCite registry (Dec2017-May2020), a prospective dataset of IIM was extracted for the clinical profile, and MSAs, immunosuppressants received, disease activity (relapses and incomplete response), and treatment-related (drugs ADRs and infections) adverse events (DRAE and TRAE) were collected and analyzed between groups. Of 214 adults (58-OM,89-DM,27-ASSD,33-PM,7-CAM), OM had a greater female preponderance (13.5:1). Raynaud's and sclerodactyly were the prime distinguishing features of OM. OM could be distinguished from PM by frequent arthritis (OR-3.2) and infrequent dysphagia (OR-0.17); DM with greater nephritis (OR-20), infrequent dysphagia (OR-0.24) and rashes (OR-0.02); and ASSD by infrequent ILD (OR-0.07), and mechanic's hand (OR-0.05). 50% fulfilled the classification criteria for ASSD in the absence of MSA testing. ANA was positive more often (PM/DM: OR-6.7) and anti-Ro52 (OR-4.5) frequent in OM. Baseline serum creatinine and acute phase reactants were higher. OM received lower glucocorticoids (0 mg/kg, p < 0.001). Overall, 90% and 84% of OM at 12 and 24 months, respectively, achieved remission, with similar DRAE and TRAE as other IIM subsets. OM can be misdiagnosed as ASSD in the absence of MSA testing. Raynaud's, sclerodactyly, and a positive ANA may identify OM and prevent overtreatment.

Sensitivity and specificity of single and combined clouds analyses compared with quantitative motor unit potential analysis.

INTRODUCTION: Turns-amplitude, number of small segments (NSS)-activity, and envelope-activity clouds are three methods of electromyography (EMG) interference pattern analysis. Our objective was to evaluate the sensitivity and specificity of each individual cloud analysis and combined clouds analysis to compare with that of quantitative motor unit potential (QMUP) analysis. METHODS: A total of 379 muscles from 100 patients were analyzed by both QMUP and clouds analyses. Calculation of sensitivity and specificity was based on the clinical diagnosis as the "gold standard." RESULTS: For discrimination of abnormal vs normal and neuropathic vs non-neuropathic, combined clouds analysis had greater sensitivity than QMUP analysis and any single cloud analysis, but there were no differences in specificity. For discrimination of myopathic vs non-myopathic, combined clouds analysis and single cloud analysis had greater sensitivity than QMUP analysis, but there were no differences in specificity. DISCUSSION: Combined clouds analysis was superior to QMUP and each single cloud analysis for distinguishing normal, myopathic, and neuropathic muscles.

Hand-held dynamometry for assessment of muscle strength in patients with inflammatory myopathies.

OBJECTIVES: Muscle weakness in idiopathic inflammatory myopathies (IIMs) is conventionally assessed using manual muscle testing (MMT). However, more objective tools must be developed to accurately and reliably quantify muscle strength in myositis patients. Hand-held dynamometry (HHD) is a quantitative, portable device with reported reliability in neuromuscular disorders. Our aim was to assess the reliability, validity and responsiveness of HHD in myositis. METHODS: Myositis patients [DM, necrotizing myopathy (NM), PM and anti-synthetase syndrome] evaluated at the University of Pittsburgh myositis centre were prospectively enrolled. Each patient was assessed at 0, 3 and 6 months for validated outcome measures of myositis disease activity and physical function. At each visit, muscle strength was assessed using both MMT and HHD (Micro FET2, Hoggan Health Industries, Draper, UT, USA). The reliability, validity and responsiveness of the HHD was assessed using standard statistical methods. RESULTS: Fifty IIM patients (60% female; mean age 51.6 years; 6 PM, 9 NM, 24 DM and 11 anti-synthetase syndrome) were enrolled. HHD showed strong test-retest intrarater reliability (r = 0.96) and interrater reliability (r = 0.98). HHD correlated significantly with the MMT score (r = 0.48, P = 0.0006) and myositis disease activity and functional measures. Longitudinal analysis showed a significant and strong association between the HHD and MMT as well as 2016 ACR/EULAR myositis response criteria (r = 0.8, P < 0.0001) demonstrating responsiveness. The mean effect size and standardized response mean of HHD was large: 0.95 and 1.03, respectively. MMT had a high ceiling effect compared with HHD. CONCLUSION: HHD demonstrated strong reliability, construct validity and responsiveness in myositis patients. External validation studies are required to confirm these findings.