Updates on the pathogenesis and molecular-targeted therapies of Still's disease.

Abstract

Still's disease is a systemic inflammatory disorder involving both innate and adaptive immunity. Although its pathogenesis remains incompletely understood, immune cells such as neutrophils, macrophages, and T cells, along with pro-inflammatory cytokines, particularly interleukin (IL)-1, IL-6, IL-18, and interferon-γ (IFN-γ), play central roles in disease development. While glucocorticoids remain the first-line treatment, the advent of molecular-targeted therapies has revolutionized management. IL-1 and IL-6 inhibitors have shown efficacy in controlling disease activity and reducing glucocorticoid dependence. However, treatment responses vary among patients due to immunological heterogeneity. Recent studies have proposed clustering patients based on clinical features, immune cell profiles, and dominant cytokine signatures to help predict therapeutic responses. In addition, novel therapies targeting IL-18, IFN-γ, and Janus kinase (JAK) signaling pathways are emerging as promising options for refractory cases. This review summarizes current insights into the immunopathogenesis of Still's disease and explores the evidence supporting molecular-targeted therapies, paving the way toward personalized treatment strategies.