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.

Unique characteristics of anti-MDA-5 associated dermatomyositis in Southern California with a large Hispanic population.

OBJECTIVES: There is little to no data about the presentation and clinical course of anti-melanoma differentiation-associated gene-5 antibody (anti-MDA-5) dermatomyositis in a primarily U.S. Hispanic population. We describe the clinical course of anti-MDA-5 dermatomyositis in our majority Hispanic population. METHODS: This is a multicenter, retrospective case series of anti-MDA-5 dermatomyositis. Patients diagnosed with anti-MDA-5 dermatomyositis from June 2015 to March 2023 at four medical centers in Los Angeles, California, were included. Demographics and clinical characteristics were obtained. Descriptive statistics, Pearson's chi-squared, Fisher's exact, Wilcoxon rank sum, and Kruskal-Wallis tests were performed as applicable. RESULTS: Thirty anti-MDA-5 dermatomyositis patients were included. Twenty-two (73 %) were Hispanic. Twenty-one patients (70 %) were female, with a median age of 40.5 years. Hispanic patients were diagnosed with anti-MDA-5 dermatomyositis at a younger age than non-Hispanic patients (p = 0.025). Inflammatory arthritis was prominent; more males were affected than females (p = 0.027). Thirteen patients (43 %) were amyopathic. Twenty-five patients (83.3 %) had evidence of interstitial lung disease (ILD), and a higher ferritin level was associated with ILD (p = 0.049). There were six deaths (20 %); five (17 %) were ascribed to rapidly progressive ILD. CONCLUSION: ILD was the most common presentation of anti-MDA-5 dermatomyositis in our cohort and was associated with higher ferritin levels. Hispanic patients had a younger age of diagnosis than non-Hispanic patients. Necrotic skin lesions and inflammatory arthritis were frequently seen. This is the first study looking at clinical phenotypes and outcomes of anti-MDA-5 dermatomyositis in a primarily Hispanic U.S. POPULATION: Future studies are needed to better understand the clinical manifestations (to promptly recognize and treat) of this population of anti-MDA-5 dermatomyositis.

Risk factors for developing calcinosis in juvenile dermatomyositis: subcutaneous and myofascial edema in initial magnetic resonance imaging.

Calcinosis is a sequela of Juvenile Dermatomyositis (JDM) with significant morbidity. A retrospective study observing risk factors for JDM calcinosis, including a possible association between higher intensity of subcutaneous and myofascial edema in initial magnetic resonance imaging (MRI) and development of calcinosis was performed at a tertiary pediatric medical center. Data from the past 20 years on JDM patients with MRIs at the time of JDM diagnosis were obtained. MRIs were individually evaluated by two pediatric musculoskeletal radiologists who blindly graded the intensity of edema on a 0-4 Likert scale. Clinical data and edema scores were compared between patients who developed calcinosis and who did not. Forty-three patients (14 with calcinosis and 29 without calcinosis) were identified. The calcinosis group contained more racial and ethnic minorities, younger ages of JDM onset and longer time to reach JDM diagnosis. Muscle enzyme levels at JDM diagnosis were lower in the calcinosis group, especially Creatinine Kinase (CK) (p = 0.047) and Alanine Aminotransferase (ALT) (p = 0.015). The median score for edema in both groups was 3 (p = 0.39) with an inter-rater reliability of 95%. There was no association between increased subcutaneous and myofascial edema in MRIs at the time of JDM diagnosis and development of calcinosis. Earlier age of JDM onset, racial and ethnic minority, and delay in JDM diagnosis could be risks for developing calcinosis. The calcinosis group presented with lower muscle enzyme levels at the time of JDM diagnosis, especially CK and ALT with statistical significance. This could reflect delay in diagnosis and treatment.

Abatacept in the treatment of localized scleroderma: A pediatric case series and systematic literature review.

BACKGROUND: Localized scleroderma (LS) is a rare chronic immune-mediated skin condition of unknown etiology characterized by an inflammatory response in the skin and subcutaneous tissues resulting in collagen deposition and subsequent fibrosis. There is no cure for LS. No therapies have been licensed specifically for the treatment of LS and the clinical management of the disease remains largely empirical. Abatacept, a recombinant fusion protein interfering with the T-cell costimulatory pathway, has been reported to be effective in adult cases of LS. We report the successful use of abatacept in a juvenile localized scleroderma (jLS) cohort and conduct a systematic literature review to evaluate the evidence supporting the use of abatacept in the treatment of LS. METHODS: We compiled retrospectively the clinical data on 8 cases of jLS that were treated with abatacept in our academic center. A systematic review protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) guidelines and has been registered with the international prospective register of systematic reviews (PROSPERO). Standardized searches of MEDLINE/PubMed and EMBASE were undertaken to identify studies reporting the use of abatacept in the treatment of LS. Heterogeneity in study design, interventions and reported outcomes necessitated a qualitative data synthesis. RESULTS: The use of abatacept was effective and safe in our cohort of jLS patients. Our standardized searches identified 30 articles, of which 3 deemed eligible for full data extraction. All 3 studies were small (total of 18 patients; mean 6 subjects per study), single center, open-label, uncontrolled and non-randomized. The Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS) identified high risk-of bias for confounding variables and blinding of assessors in each of the 3 studies evaluated and in our pediatric case series. CONCLUSIONS: The evidence-base to support the use of abatacept in the treatment of LS is currently limited and clinical practice guidelines should take a measured approach to such recommended therapy. Nonetheless, as the empirical evidence on the clinical effectiveness of abatacept in the treatment of LS accumulates, a double-blind placebo-controlled randomized clinical trial is necessary to formally evaluate the observations documented by case-based reports.