The unique aspects of presentation and diagnosis of hemophagocytic lymphohistiocytosis in adults.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) was initially described as an inflammatory condition affecting young children but is increasingly diagnosed in adults. Presenting features such as fever, cytopenias, phagocytosis, elevated ferritin, and increased levels of soluble IL-2 receptor are common in both age groups, but the prevalence of several clinical and biochemical criteria differ between pediatric and adult patients. Specifically, an elevated ferritin level does not have the same specificity for HLH in adults, and many other inflammatory conditions need to be considered in the differential. In contrast to the high incidence of infectious triggers seen in pediatric HLH, HLH in adults is often precipitated by a hematologic malignancy. Malignancy-associated HLH has unique manifestations and a uniformly very poor prognosis. Given these differences, diagnostic scoring systems unique to adult HLH have been proposed, and additional prognostic clinical and immunologic parameters are being explored. Although a genetic predisposition is increasingly found to underlie cases of adult-onset HLH, the mutations are less likely to be bi-allelic and differ slightly from those seen in pediatric cases of familial HLH. The facilitating genetic and environmental factors governing presentation of HLH in adults remain elusive. Understanding the clinical aspects and pathophysiology specific to adults with HLH is necessary to tailor therapies derived in pediatric disease to this under-recognized population.