Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by severe hyperinflammation, leading to endorgan damage and death in the absence of treatments directed at suppressing the overactive immune system. The study of mouse models and human biospecimens has provided insights into disease pathophysiology and enabled investigations of novel therapeutic strategies. Nevertheless, clinical outcomes remain suboptimal. Additional research is required to further our understanding of this highly heterogeneous disease in order to develop improved diagnostic and prognostic tools and identify and implement targeted and less toxic treatments. In this article, written on behalf of the Histiocyte Society, we highlight six key areas of ongoing research, including the remaining questions in each area. We also outline the challenges of global dissemination and implementation of this research and call for the establishment of local, regional, and national cooperative groups aimed at providing education for physicians and targeted diagnostic and clinical guidelines. Finally, we discuss the role of international societies, including the Histiocyte Society, in nucleating this work to ensure coordinated efforts aimed at improving outcomes for patients with HLH worldwide.