Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a frequently fatal and likely underdiagnosed disease involving a final common pathway of hypercytokinemia, which can result in end-organ damage and death. Although an early diagnosis is crucial to decrease mortality, the definitive diagnosis is often challenging because of the lack of specificity of currently accepted diagnostic criteria and the absence of confirmatory gold standards. Because of the wide range of laboratory assays involved in the diagnosis of HLH, practicing pathologists from a broad spectrum of clinical specialties need to be aware of the disease so that they may appropriately flag results and convey them to their clinical counterparts. Our article summarizes these new advances in the diagnosis of HLH and includes a review of clinical findings, updated understanding of the pathogenesis, and promising new testing methods.

Hemophagocytic Syndrome and Critical Illness

“…For example, pancytopenia and hypertriglyceridemia are thought to be a result of excessive levels of TNFα and IFNγ, which suppress hematopoiesis and inhibit lipoprotein lipase, respectively (49). On the other hand, prolonged fevers are most likely driven by high levels of IL-1 and IL-6 levels (reviewed in (3)).…”

Malignancy‐associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes

“…A highly stimulated and defective inflammatory response involving 3 main pathways is central to the initiation and propagation of HLH, (1) hyperactivation of CD8+ T lymphocytes and macrophages, (2) proliferation and infiltration of these cells into organs and tissues, and (3) uncontrolled hypercytokinemia 1–4 . Patients present with a spectrum of features of an acute illness including fever, cytopenias, spleen and/or liver enlargement, coagulopathy, encephalopathy, and transaminits 3,5–7 .…”

Hemophagocytic lymphohistiocytosis and pulmonary alveolar proteinosis in a 13-month-old boy with lysinuric protein intolerance

“…[1] HLH was first described by Farquhar and Claireaux in 1952 [2] and is characterized by prolonged fever, cytopenias, hepatosplenomegaly, abnormal lab values and the presence of hemophagocytosis (for complete diagnostic criteria see [3] ). HLH can be dichotomized into primary (genetic) or secondary (acquired) causes and is associated with many underlying conditions affecting all age groups regardless of the principal etiology.…”

“…HLH can be dichotomized into primary (genetic) or secondary (acquired) causes and is associated with many underlying conditions affecting all age groups regardless of the principal etiology. [1,4] Primary HLH occurs due to genetic aberrations that affect the perforin-mediated cytotoxic abilities of T cells and natural killer cells, whereas, acquired HLH typically occurs in adults secondary to infection, malignancy, rheumatologic disease or immune suppression. [5] Several hereditary immunodeficiency syndromes predispose patients to HLH and HLH is frequently the first manifestation of such diseases.…”