Advancing Precision Medicine in Adult-Onset Still's Disease: Insights into Biomarkers, Therapies, and COVID-19 Impacts.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disorder characterized by spiking fevers, arthralgia, and a transient salmon-pink rash, with an incidence of 0.16-0.4 per 100,000. AOSD shares overlapping clinical and immunological features with systemic juvenile idiopathic arthritis (sJIA), supporting a disease continuum and shared treatment approaches. The COVID-19 pandemic has impacted AOSD care, with SARS-CoV-2 infection and vaccination occasionally triggering disease flares, necessitating adaptive management strategies. Driven by innate immune dysregulation and overproduction of proinflammatory cytokines (IL-1, IL-6, IL-18), AOSD presents in systemic and articular phenotypes, with severe complications like macrophage activation syndrome (MAS), fulminant hepatitis, and parenchymal lung disease. Diagnosis, based on Yamaguchi or Fautrel criteria and biomarkers (ferritin, IL-18), is challenging due to nonspecific symptoms. Biologic therapies (anakinra, canakinumab, tocilizumab) achieve remission in 80-90% of systemic cases. This review synthesises diagnostic challenges, novel biomarkers (e.g., gasdermin D), and emerging therapies (e.g., IL-18 binding protein), emphasising precision medicine and future research needs.