Adult haemophagocytic lymphohistiocytosis: a review

Abstract

Haemophagocytic 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. This review aimed to update knowledge on adult HLH pathophysiology, identify the numerous causes and help clinicians make early diagnosis and initiate treatment. Using Embase, we searched relevant articles published from 1 January 2010 to 31 October 2019, with the MESH term ‘haemophagocytic lymphohistiocytosis; macrophagic activation syndrome, adult’. 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 26.5–74.8%. HScore is more efficient than HLH-2004 criteria to identify HLH, with diagnostic sensitivity and specificity 90% and 79%, respectively. 18-fluorodeoxyglucose positron emission tomography–computed tomography 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. 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.

Etoposide-based therapy for severe forms of COVID-19

“…The CSSs are associated with hemophagocytic lymphohistiocytosis (HLH) which can be primary or familial (pHLH) or secondary, acquired or reactive (sHLH) [5]. The sHLH, occurring frequently after an infection, are life-threatening syndromes of extreme immune activation leading to a multiorgan failure and a severe hypercytokinaemia [6]. The revised criteria for HLH diagnosis include fever, splenomegaly, bicytopenia, hypertriglyceridaemia or hypofibrinogenaemia (or both), haemophagocytosis, ferritin ≥500 µg/L, low NK cell activity, and soluble IL-2 receptor ≥2400 U/mL).…”

Clinical Characteristics and Prognostic Factors in Patients with Hemophagocytic Syndrome

“…The HPS mortality rate is between 26.5% and 74.8% according to different published series [6][7][8][9][10][11]. In general malignant neoplasms underlying HPS, hyperferritinemia, thrombocytopenia, older age at diagnosis of HPS, hypertriglyceridemia, and prolonged prothrombin time greater than 3 seconds are considered to be adverse prognostic factors [7][8][9][10][11][12][13][14][15][16].…”

Consequences of treatment for hemophagocytic lymphohistiocytosis in a patient with undiagnosed Gaucher disease Type 1

“…Hemophagocytic lymphohistiocytosis (HLH) is considered a hyperactivation of the immune system, involving disorders of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs), and macrophages (Al‐Samkari & Berliner, 2018; Yildiz, Van Den Neste, Defour, Danse, & Yombi, 2020). It can present with hepatomegaly, splenomegaly, and cytopenias alongside other signs and symptoms that include fever, neurologic dysfunction, hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia (Supporting Information Table S1) (Yildiz et al, 2020). Pathologic hemophagocytosis may be seen in a biopsy sample (bone marrow, spleen, or lymph node).…”