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Clinical features and diagnosis of hemophagocytic lymphohistiocytosis

Kenneth L McClain, MD, PhD
Olive Eckstein, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. It most frequently affects infants from birth to 18 months of age, but the disease is also observed in children and adults of all ages. HLH can occur as a familial or sporadic disorder, and it can be triggered by a variety of events that disrupt immune homeostasis. Infection is a common trigger both in those with a genetic predisposition and in sporadic cases.

Prompt initiation of treatment is essential for the survival of affected patients. Often the greatest barrier to a successful outcome is a delay in diagnosis, which is difficult because of the rarity of this syndrome, the variable clinical presentation, and the lack of specificity of the clinical and laboratory findings.

The clinical features and diagnosis of HLH and a related disorder, the macrophage activation syndrome (MAS), will be discussed here. The management of patients with these disorders is discussed separately. (See "Treatment and prognosis of hemophagocytic lymphohistiocytosis".)


Terms used to describe HLH and related syndromes have evolved since the original patient was described as having "familial hemophagocytic reticulosis" in 1952.

Use of the term "primary HLH" to denote the presence of an underlying genetic disorder and "secondary HLH" to denote presence of the HLH phenomenon occurring secondary to another condition has caused a great deal of confusion among clinicians. Both primary and secondary HLH can be triggered by infections or other immunologically activating events, and gene mutations can be found in individuals of any age and with any family history. In practice, distinction between primary and secondary HLH is not essential for the initial diagnosis and management. However, identification of a gene mutation may be useful for subsequent management. (See 'Evaluation and diagnostic testing' below.)


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