MDA5-associated juvenile dermatomyositis and interstitial lung disease from rapidly progressive to silent: a report of three cases in South African children and a review of the literature

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare pediatric autoimmune disease. A distinct clinical phenotype is associated with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies, which are linked to features such as arthritis, ulcerative skin lesions, and a heightened risk of interstitial lung disease (ILD), including its rapidly progressive form (RP-ILD). Despite increased recognition of this phenotype in East Asian, European, and North American populations, significant gaps remain in understanding its pathogenesis, and no consensus has been reached regarding optimal treatment strategies. Moreover, data on anti-MDA5-associated JDM in African populations are nonexistent. CASE PRESENTATION: We report the first three documented cases of anti-MDA5-positive JDM with ILD in African children. All patients exhibited characteristic extramuscular manifestations, and all had pulmonary involvement, which was rapidly progressive in two children, one of whom died. The clinical course, diagnostic findings, and treatment strategies are discussed in the context of existing literature. METHODS: A review of the literature was performed to evaluate the prevalence, clinical presentation, and treatment approaches for RP-ILD in anti-MDA5-associated JDM across different populations. CONCLUSION: These cases highlight the wide heterogeneity of clinical phenotypes associated with anti-MDA5 autoantibodies in JDM. Given this variability, individualized monitoring and management strategies are essential to optimize outcomes.