Phagocytes Out of Control: Macrophage Activation Syndrome After the Use of Biologic Agents in the Treatment of Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis (sJIA) is an arthritis of unknown origin in children younger than age 16 years. While there is no definitive cure, the prognosis has improved with the development of biologic agents targeting interleukins (ILs). These drugs have shown positive outcomes but are associated with significant adverse effects, notably macrophage activation syndrome (MAS), which is a severe condition involving excessive immune activation. We sought to identify recent literature examining MAS as an adverse effect of sJIA treatment with biologics and to summarize the current understanding of the prevalence, pathophysiology, diagnosis, and management of MAS in the context of sJIA. Findings indicate that the incidence of MAS when using IL-1 and IL-6 inhibitors, particularly within the first 6 months of treatment, is relatively common; although, it is difficult to definitively identify biologic therapy as the cause. While biologics offer substantial benefits, they also require vigilant monitoring due to the increased risk of MAS. [ Pediatr Ann . 2025;54(7):e249–e253.]