INTRODUCTION: Familial lymphophagocytic histiocytosis (FHL) is an autosomal-recessive immunologic disorder that is fatal if untreated. The quoted incidence is 1.2 in 1 000 000; fewer than 1 of 3 patients are diagnosed while alive. The true incidence of FHL may be much higher.
OBJECTIVE: With this project we aimed to identify consensus information required for early recognition and diagnosis of patients with FHL to initiate life-saving treatment.
METHODS: An extensive Medline search that covered the last 20 years produced 17 relevant articles. The hemophagocytic lymphohistiocytosis 2004 protocol produced by the American Histiocyte Society provided additional information.
RESULTS: From this review, the consensus diagnostic criteria for FHL are (1) familial disease/known genetic defect, (2) clinical and laboratory criteria (5 of 8 criteria), (3) fever, (4) splenomegaly, (5) cytopenia in ≥2 cell lines, (6) hypertriglyceridemia and/or hypofibrinogenemia, (7) high ferritin level, (8) high levels of soluble CD25 (interleukin 2 receptor), and (9) hemophagocytosis in bone marrow, cerebrospinal fluid, or lymph nodes. Results of tests of initial bone marrow aspirate may be inconclusive, and repeated ones may be necessary. Half of the patients have abnormal cerebrospinal fluid findings. Several symptoms and laboratory findings provide supportive evidence.
CONCLUSIONS: Diagnostic criteria and supportive features are consistent throughout literature and are aided by the recent addition of genetic and protein-based testing. Diagnostic difficulty lies in the lack of pathognomonic features or specific diagnostic tests for FHL. Not all features present at the initial stage. Treatment should be initiated in cases of strong clinical suspicion.
Submitted by Caroline Gholam
- Copyright © 2008 by the American Academy of Pediatrics