Macrophage Activation Syndrome in Childhood Inflammatory Disorders: Diagnosis, Genetics, Pathophysiology, and Treatment

Abstract

Macrophage activation syndrome (MAS) is a life-threatening inflammatory condition, belonging to the spectrum of hemophagocytic lymphohistiocytosis (HLH), which may severely complicate the course of rheumatologic diseases, mainly systemic juvenile idiopathic arthritis. Although the pathophysiology of MAS is still not completely understood, it is characterized by an abnormal proliferation of T lymphocytes and macrophages, responsible for cytokine overproduction and hemophagocytosis. Because MAS may be rapidly fatal, its prompt recognition is imperative in order to immediately start adequate treatment. This review will overview the main features of MAS occurring in the context of childhood inflammatory conditions, discussing the recent updates in diagnosis, pathophysiology, and management. Recently, several diagnostic tools have been developed to recognize MAS in the context of pediatric inflammatory disorders. These are largely based on routinely available clinical and laboratory features and may aid physician in clinical practice. Progress in understanding the pathophysiology of MAS led to a significant improvement in identifying novel therapies targeting pro-inflammatory cytokines, a less toxic approach for children with MAS. In the future, tailored therapy based on the recognition of genetic predisposition, underlying disorder, triggers, and biomarkers will likely improve the outcome of pediatric patients with MAS/sHLH.