Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of defective apoptosis, a disruption of the regulatory pathway that terminates immune and inflammatory responses. Fever, cytopenia, splenomegaly, and/or hemophagocytosis are typical findings of this syndrome. HLH can be induced by genetic disorders (familial) or secondary causes. Familial HLH is rare, while secondary causes in adults include infection, autoimmunity, and malignancy. HLH in adults tends to be confused with or misdiagnosed as sepsis, mainly due to similar clinical manifestations and laboratory findings, which make it difficult to diagnose HLH rapidly and adopt immunosuppressive agents and/or chemotherapy adequately. Treatment of pediatric HLH using HLH-2004 or multi-agent chemotherapy can be applied in adult patients, although the dose and type of drug need to be adjusted. It is highly recommended that allogenic hematopoietic stem cell transplantation should be used in patients who become reactivated or are refractory to the initial treatment as soon as possible to improve survival. Future clinical trials are warranted to determine more suitable treatments for adult patients with HLH.

Keywords: Hemophagocytic lymphohistiocytosis; Hemophagocytic syndrome.

Fig. 1

The immunologic response is different between the normal host versus patients with hemophagocytic lymphohistiocytosis.

Fig. 2

The clinical manifestations of severe inflammatory diseases vary according to the genetic polymorphisms and mutations.Abbreviations: HLH, hemophagocytic lymphohistiocytosis; IAHS, infection-associated hemophagocytic syndrome; MAHS, malignancy-associated hemophagocytic syndrome; MAS, macrophage activation syndrome.