Current myositis clinical trials and tribulations.

With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical trials in idiopathic inflammatory myopathies (myositis) over the last three years reaching as many as five trials per site. These trials share similar design and inclusion/exclusion criteria resulting in a competitive clinical trial landscape in myositis. While these are exciting times for the myositis field, we have a number of concerns about the design and conduct of the myositis trials. These include competitive landscape, lengthy placebo arms, underrepresentation of minority groups among participants, use of patient reported outcome measures with limited/no data on validity in myositis, antiquated disease classification criteria, and unclear performance of the ACR/EULAR Myositis Response Criteria in skin-predominant patients despite inclusion of these patients in trials. In this viewpoint, we further discuss these concerns and offer potential solutions such as including patient perspectives in the trial design and adoption of innovative frameworks.

Pathological autoantibody internalisation in myositis.

OBJECTIVES: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption. METHODS: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing. RESULTS: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets. CONCLUSIONS: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.

Breaking Down Statin Myopathy: Understanding the Self-Limited and Autoimmune Subtypes.

Statins are widely used crucial drugs for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Although generally well tolerated, statin intolerance can unfortunately limit statin use, with statin-associated muscle symptoms (SAMS) being the most common side effect associated with its discontinuation. Statin intolerance is an inability to tolerate a dose of statin required to sufficiently reduce an individual's cardiovascular risk, limiting the effective treatment of patients at risk of or with cardiovascular disease (CVD). Statin myopathy is a broad entity encompassing self-limited/toxic and autoimmune etiologies. As statins are a mainstay of therapy in those with or at risk for CVD and offer a mortality benefit, it is critical to determine whether one's symptoms are truly statin-associated before discontinuing the drug. This review article aims to provide an update on the epidemiology, pathophysiology, clinical features, diagnosis, evaluation, and management of statin myopathy and to elucidate key differences between autoimmune and self-limited types.

Extracorporeal Membrane Oxygenation for Acute Lung Injury in Idiopathic Inflammatory Myopathies-A Potential Lifesaving Intervention.

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units (ICU). Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome can be lifesaving. We aimed to report a case series of IIM patients that received ECMO. METHODS: Patients with IIM from tertiary care centers in Belgium, Canada, Denmark, United States, and Sweden who underwent ECMO were reviewed to describe clinical characteristics, disease outcomes and hospitalization course. Clinical characteristics at admission and during ICU stay including ECMO complications and mortality causes were summarized. RESULTS: The study included 22 patients (50% female, mean±SD age at admission 47 ± 12 years) with anti-MDA5 positive dermatomyositis (68%), anti-synthetase syndrome (14%), polymyositis (9%), overlap myositis (5%) and non-MDA5 dermatomyositis (5%). Patients had low comorbidity scores and 46% had received immunosuppression before their ICU admission. Eight (36%) patients died in the ICU, six (27%) were bridged to recovery and eight (36%) were bridged to transplant. When comparing patients bridged to recovery and those who died in the ICU, those who died were older (p= 0.03) and had higher median Charlson comorbidity index scores (p= 0.05). Both groups had similar frequencies of ECMO-related complications (33% vs 50%, p= 0.94). CONCLUSION: In the patients exposed to ECMO in this case series, 14 were successfully bridged to recovery or transplant, while 8 died in the ICU. Large studies are needed to collect data on clinical outcomes in patients with IIM-ILD exposed to ECMO to identify the best candidates for the intervention.

Prevalence and Risk Factors of Post-Acute Sequela of COVID-19 in Adults with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: Incidence and manifestations of post-acute sequelae of COVID-19 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. METHODS: Persons ≥18 years with systemic autoimmune diseases were recruited into a national, prospective cohort of SARS-CoV-2 vaccination between 12/2020-4/2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QoL) impact; PASC was defined as ≥1 symptom persisting for >12 weeks. PASC syndromes were mapped via overlapping symptom domains. Characteristics were compared between participants who did versus did not report PASC. RESULTS: Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded >12 weeks following reported infection. Respondents were 1.62% female, 90.2% white, median (IQR) age 48(40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). 89/299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an impact on QoL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2[2-3] versus 3[2-3]; p<0.001) and more reinfections (16.9% versus 5.7%; p=0.004). CONCLUSION: 29.8% of persons with systemic autoimmune disease in a large real-world cohort reported PASC, often affecting QoL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.

Patient Perspectives of the Manifestations and Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis: An Observational Survey.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders classically characterized by proximal skeletal muscle inflammation leading to weakness, but they often possess additional systemic manifestations such as cutaneous, pulmonary, and articular disease.1 Although originally dichotomized as either dermatomyositis (DM) or polymyositis, the discovery of new myositis-specific antibodies (MSA) and myositis-associated antibodies has led to the delineation of more refined IIM patient subgroups.

Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

Decoding the Intricacies of Statin-Associated Muscle Symptoms.

PURPOSE OF REVIEW: Hyperlipidemia is the major cardiovascular morbidity and mortality risk factor. Statins are the first-line treatment for hyperlipidemia. Statin-associated muscle symptoms (SAMS) are the main reason for the discontinuation of statins among patients. The purpose of this review is to guide clinicians to recognize the difference between self-limited and autoimmune statin myopathy in addition to the factors that potentiate them. Finally, treatment strategies will be discussed. This review mostly focuses on new data in the past 3 years. RECENT FINDINGS: Recent findings suggest that SAMS is a complex and multifactorial condition that involves mitochondrial dysfunction, oxidative stress, and immune-mediated mechanisms. Effective management of SAMS requires a thorough evaluation of the patient's symptoms, risk factors, and medication history, as well as consideration of alternative treatment options. While statins are effective in reducing the risk of cardiovascular events, their use is associated with a range of adverse effects, including SAMS.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.

OBJECTIVES: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies. METHODS: Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies. RESULTS: Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer. CONCLUSIONS: Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.

OBJECTIVES: Myositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients. METHODS: RNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies. RESULTS: A set of 135 genes, including SCRT1 and MADCAM1, was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei. CONCLUSIONS: Based on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study.

Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis.

OBJECTIVES: Inflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis. METHODS: Bulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM). RESULTS: Unsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway. CONCLUSIONS: We identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis.

The pattern of MHC class I expression in muscle biopsies from patients with myositis and other neuromuscular disorders.

OBJECTIVE: Diagnostic muscle biopsies are routinely immunostained for major histocompatibility complex class I (MHC-I) protein. In this study we analysed the prevalence and patterns of MHC-I immunostaining in biopsies from patients with different types of myopathies and neurogenic disorders. METHODS: All 357 diagnostic muscle biopsies processed at the Johns Hopkins Neuromuscular Pathology Laboratory from August 2013 to January 2017 were immunostained for MHC-I. The prevalence and patterns of MHC-I immunostaining were compared between patients with histologically normal muscle biopsies (n = 31), idiopathic inflammatory myopathies (IIMs; n = 170), non-inflammatory myopathies (n = 60) and neurogenic disorders (n = 96). RESULTS: MHC-I immunostaining was abnormal in most patients with DM (98%), sporadic IBM (sIBM; 100%), immune-mediated necrotizing myopathy (IMNM; 100%) and polymyositis (77%). In contrast, MHC-I immunostaining was less frequently present in non-inflammatory myopathies (32%) or neurogenic disorders (30%). Overall, abnormal MHC-I immunostaining had a sensitivity of 0.95 and a specificity of 0.82 for diagnosing IIMs. A focal MHC-I staining pattern was associated with IMNM, whereas a global pattern was more prevalent in sIBM and a perifascicular pattern was significantly more common in dermatomyositis. Among 18 DM biopsies without perifascicular atrophy, 50% had a perifascicular MHC-I staining pattern. Sarcoplasmic upregulation staining was more common than sarcolemmal staining across all groups. CONCLUSION: MHC-I immunostaining was useful to distinguish IIMs from non-inflammatory myopathies or neurogenic disorders. Of note, a perifascicular MHC-I staining pattern was present only in those with DM, including half of those without perifascicular atrophy; many of these biopsies may not otherwise have been diagnostic for DM.

Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy that commonly manifests with proximal muscle weakness and is associated with extramuscular pathology, including characteristic skin lesions such as Gottron's papules and heliotrope rash, as well as lung, gastrointestinal, joint, and cardiac involvement. Systemic corticosteroids are a cornerstone of therapy, and more recently intravenous immunoglobulin (IVIG; OCTAGAM®) has been approved by the US Food and Drug Administration for the treatment of adults with DM. Both steroids and IVIG represent nonspecific anti-inflammatory therapy, and more targeted approaches are lacking. Transcriptomics has identified upregulation of interferon (IFN)-regulated genes as key features of both adult DM and juvenile DM (JDM). Accordingly, blocking IFN signalling through inhibition of the Janus kinase (JAK) pathway represents a potential treatment option for DM. Placebo-controlled trial data assessing the use of JAK inhibitors for the treatment of DM are limited; as such, a systematic literature review was undertaken to assess the evidence of JAK inhibitors in the treatment of patients with DM. Terms related to DM and JAK inhibitors were searched using PubMed, Embase, Web of Science, Scopus, and Dimensions to identify peer-reviewed publications reporting patients with DM who were treated with a JAK inhibitor. Baseline demographics, clinical characteristics, and treatment outcome data were extracted. A total of 48 publications reporting 145 unique patients (adult DM, n=84; JDM, n=61) were identified. Among cases of adult DM, 61 of 84 (73%) had refractory skin disease at baseline, and all (61 of 61) reported improvement in cutaneous symptoms. Of patients with adult DM, 16 of 84 (19%) had refractory muscle disease at baseline, and all (16 of 16) reported improvement in muscle symptoms. In patients with adult DM complicated by interstitial lung disease (ILD; n=33), 31 (94%) patients improved with JAK inhibitor treatment. Among cases of JDM with refractory skin disease at baseline (60 of 61), most patients (57 of 60; 95%) showed improvements in skin symptoms after JAK inhibitor treatment. Of patients with JDM with refractory muscle disease at baseline (36 of 61), most (30 of 36; 83%) reported improvement in muscle symptoms. Four patients with JDM and ILD experienced improvement in lung disease activity following treatment with a JAK inhibitor. Among both DM and JDM cases, all patients (17 with DM and 16 with JDM) who had elevated serum IFN and/or IFN-stimulated gene expression at baseline showed reduction in IFN or IFN gene expression. Although the conclusions that can be drawn from this analysis are limited because of the differences in assessments used across publications, overall treatment of patients with DM or JDM with a JAK inhibitor was associated with significant improvement of a wide range of DM manifestations, including skin lesions, muscle weakness, and ILD. Our systematic literature review suggests that JAK inhibitors may be a viable treatment option for DM/JDM, and randomised controlled trials are necessary to confirm these findings.

Anti-MDA5-positive dermatomyositis and remission in a single referral centre population.

OBJECTIVES: To describe a single-centre North American adult cohort of anti-MDA5-positive dermatomyositis patients, with emphasis on drug-free long-term remission. METHODS: We conducted an observational retrospective cohort study of anti-MDA5-positive DM patients. All consented patients seen in the Johns Hopkins Myositis Centre from 2003-2020 with suspected muscle disease were routinely screened for myositis-specific autoantibodies. All sera were screened for anti-MDA5 autoantibodies by line blot; positives were verified by enzyme-linked immunoassay. Patients whose sera were anti-MDA5 positive by both assays (n=52) were followed longitudinally. If clinical status was unavailable, structured telephone interviews were conducted. Clinical remission was defined as being off all immunosuppression >1 year while remaining asymptomatic. RESULTS: 38/52 (73%) of the patients were women with a median age at disease-onset of 47 (IQR 40-54). Twenty-five of the patients (48%) were White, 16 (30%) were Black and 3 (6%) were Asian. Most patients (42/52, 80%) had interstitial lung disease, defined by inflammatory or fibrotic changes on high resolution computed tomography (HRCT). 18/52 (35%) of patients required pulse-dose methylprednisolone, 4/52 (8%) experienced spontaneous pneumothorax/pneumomediastinum, 6/52 (12%) required intubation, and 5/52 (10%) died. Over longitudinal follow-up (median 3.5 years), 9 (18%) patients achieved clinical remission. The median time from symptom onset to clinical remission was 4 years, and the median duration of sustained remission was 3.5 years (range 1.4-7.8). No demographic or disease characteristics were significantly associated with remission. CONCLUSIONS: In this single centre, tertiary referral population of anti-MDA5-positive dermatomyositis, ~20% of patients experienced long-term drug-free remission after a median disease duration of 4 years. No clinical or biologic factors were associated with clinical remission.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Racial disparities in skin tone representation of dermatomyositis rashes: a systematic review.

OBJECTIVE: This systemic review assesses skin tone representation in images of DM rashes in medical education literature. METHODS: A review was performed of 59 dermatology, 11 neurology, 10 neuromuscular, 7 rheumatology and 6 internal medicine textbooks published between 2011 and 2021 and 3 online image databases (UpToDate, VisualDx and DermNet NZ) that were available through an online medical school library. After extracting images, images with poor lighting or unclear rashes were removed. Authors graded skin tone independently on the Massey and Martin Skin Colour Scale (MMSCS) from 1 (very light) to 10 (very dark). The median score was taken for a final score, grouped within MMSCS 1-2, 3-4, 5-7 or 8-10. Inter-rater reliability was assessed using Kendall's coefficient of concordance (W). RESULTS: Six hundred and twenty-one images were extracted after reviewing 93 textbooks and 3 online databases. Of the 561 images analysed, 73.1% of images represented MMSCS 1-2, followed by 3-4 (13.4%), 5-7 (11.8%) and 8-10 (1.8%). Inter-rater reliability was high (W = 0.835). Of the images in MMSCS 5-10, 59.2% were in online databases and 80.6% of textbook images were in dermatology books. CONCLUSIONS: Patients with lighter skin tones were represented in a higher number of DM-related educational materials compared with patients with darker skin tones. Our findings add to current research implicating that darker skin tones are under-represented in cutaneous educational materials, specifically for DM. This leads to the inability to properly characterize skin involvement in DM and may lead to inappropriate exclusion from clinical trials due to erroneous skin scoring.

Prevalence of avascular necrosis in idiopathic inflammatory myopathies: a single-centre experience.

OBJECTIVES: To assess the prevalence of avascular necrosis (AVN) in a large cohort of patients with idiopathic inflammatory myopathies (IIM) and define the major associated risk factors. METHODS: We retrospectively reviewed the electronic medical records of all patients with a definitive diagnosis of IIM enrolled in our registry between 2003 and 2017, and followed until 2020. Pertinent demographic, clinical, serologic and imaging data were collected. A matched group of patients without AVN was then selected for comparison. RESULTS: A total of 1680 patients were diagnosed with IIM. Fifty-one patients developed AVN, with an overall prevalence of 3%. Musculoskeletal MRI was available for 1085 patients and AVN was present in 46 patients (43 lower extremities and 3 upper extremities MRI studies), with a relative prevalence of 4.2%. Most patients with AVN were Caucasian females (57%) with a mean (s.d.) age at diagnosis of 44.5 (12.4) years. Sixty-one percent had DM and 29% had PM. The median time from onset of IIM to diagnosis of AVN was 46 months. The hip joint was most commonly involved in 76% of cases, followed by the knee joint in 15% and shoulder joint in 9%. Some 81% of patients were asymptomatic. Established risk factors for AVN were not found to be associated with the development of AVN in IIM patients. CONCLUSION: Although mostly asymptomatic and incidental, the overall prevalence of AVN in IIM was 3% and the prevalence by MRI was 4.2%. None of the established risk factors was found to be associated with AVN development.

Rapidly progressive interstitial lung disease in patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis: serial changes on HRCT.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies in patients with dermatomyositis are associated with rapidly progressive interstitial lung disease (RP-ILD). Computed tomography (CT) plays a central role in the diagnosis of RP-ILD and may help characterize the temporal changes. METHODS: We report five anti-MDA5-positive dermatomyositis patients with serial CT scans spanning their acute RP-ILD disease course. RESULTS: Our case series highlights the variable imaging pattern that can manifest in this setting, including diffuse alveolar damage and nonspecific interstitial pneumonia patterns. Three patients in our series died within 4 months of their disease onset, whereas the other two patients survived. CONCLUSION: The serial CT changes in anti-MDA5 disease are dynamic and variable; therefore, it is imperative to maintain a broad differential when faced with these HRCT patterns to improve the diagnosis and management of this underrecognized entity.