Clinical Pearls & Morning Reports
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of hyperactive immune activation that is characterized by high levels of cytokines, which reflect activation of T cells and macrophages. Read the latest Case Records of the Massachusetts General Hospital here.
Q: Name a laboratory abnormality that would lead one to consider a diagnosis of HLH.
A: A markedly elevated ferritin level leads one to consider the diagnosis of HLH syndrome. In a retrospective review of hyperferritinemia, which was defined by a ferritin level greater than 10,000 ng per milliliter, the most common diagnosis in children (occurring in 49% of cases) was HLH. However, in adults, the most common disorder was hematologic cancer (occurring in 26% of cases), and HLH was diagnosed in only 14% of cases.
Q: Describe a feature that distinguishes macrophage activation syndrome from HLH.
A: The pathophysiological features of macrophage activation syndrome are very similar to those of HLH, but macrophage activation syndrome manifests in the context of a preexisting rheumatologic disorder.
A: The triggers for HLH are all associated with dysregulation of the immune system and include immunodeficiency syndromes (e.g., the Chédiak–Higashi syndrome or Griscelli’s syndrome), rheumatologic disorders, HIV infection, Epstein–Barr virus infection, and hematologic cancer. HLH is more common among infants and children than among adults, largely because primary HLH, which denotes the presence of an underlying genetic mutation, typically appears early in childhood on exposure to viral infections. The distinction between primary and secondary HLH is not always useful, since both are often triggered by infections and both often have underlying genetic mutations that can confer a predisposition to the syndrome.
A: The diagnostic criteria include fever (present in 95% of patients), splenomegaly (89%), bicytopenia (92%), hypertriglyceridemia or hypofibrinogenemia (90%), hemophagocytosis (82%), low or absent natural-killer (NK)–cell activity (71%), elevated soluble CD25 (interleukin-2 receptor α chain) level (71%), and a ferritin level greater than 500 ng per milliliter (94%). Because adults are less likely than infants and children to have primary HLH and more likely to have an underlying predisposing disease, alternative criteria for the diagnosis of HLH have been defined. These criteria include fever, organomegaly, cytopenias, elevated ferritin levels, elevated lactate dehydrogenase levels, the presence of hemophagocytosis in the bone marrow aspirate, and most important, the presence of an underlying predisposing condition, such as a hematologic cancer or infection.