Adult haemophagocytic lymphohistiocytosis: a Review

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by hyperimmune response. The mortality is high despite progress being made in the diagnosis and treatment of the disease.

Aim: This review aimed to update knowledge on adult HLH pathophysiology, identifiy the numerous causes, and help clinicians make early diagnosis and initiate treatment.

Design and methods: Using Embase, we searched relevant articles published from January 1, 2010 to October 31, 2019, with the MESH term « hemophagocytic lymphohistiocytosis; macrophagic activation syndrome, adult ».

Results: The mean age at presentation is about 50 years, with a male predominance. The most frequent disease associations are haematological diseases, viral or bacterial infections, and autoimmune diseases. The pathophysiologic mechanism is probably the combination of inherited genetic mutations and extrinsic triggers. The mortality rate is 26.5% to 74.8%. H-score is more efficient than HLH-2004 criteria to identify HLH, with diagnostic sensitivity and specificity 90% and 79%, respectively.18F-FDG PET/CT is potentially useful for detecting underlying disease and the extent of secondary HLH. Disease-specific treatment should be given as soon as possible. Treatment with corticosteroids combined or not with etoposide is the mainstay of treatment. Monoclonal antibodies and JAK pathway inhibitors show promise of being effective.

Conclusion: In adult HLH, infectious diseases, autoimmune disease and malignancy should be suspected so that disease-specific treatment can be given promptly. Treatment with corticosteroids combined or not with etoposide is the mainstay of treatment, but new therapies show promise of being effective.

Keywords: alemtuzumab; autoimmune disease; emapalumab; genetic; hemophagocytic lymphohistiocytosis; infection; macrophagic activation syndrome; malignancy; ruxolitinib.