Hemophagocytic Syndrome and Critical Illness: New Insights into Diagnosis and Management

Abstract

Hemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous group of diseases that are characterized by a hyperinflammatory state due to uncontrolled T cell, macrophage, and histiocyte activation, accompanied by excessive cytokine production. This rare condition is almost uniformly fatal unless promptly recognized and treated. Much progress has been made in the last two decades in our understanding of the mechanisms underlying familial, and to a lesser extent, acquired cases of HLH. Recurrent mutations in more than 10 different genes have now been identified, involving biological pathways converging on intracellular vesicle trafficking and cytolytic granule exocytosis. Mechanisms underlying the majority of patients with acquired HLH, however, remain elusive, hampering both diagnostic evaluation and therapeutic management of these patients. Given that the majority of intensive care unit (ICU) patients with sepsis or multiorgan failure share many features of HLH, it is especially critical for pediatric and adult intensivists to be able to recognize patients with bona fide HLH and initiate treatment without delay. In this article, we review our current understanding of the pathophysiology, clinical testing, diagnosis, and treatment of patients with HLH, especially as it pertains to the care of critically ill patients in pediatric and medical ICUs.

Keywords: HPS; ferritin; hemophagocytic lymphohistiocytosis; hemophagocytic syndrome.

Figure 1

Extensive hemophagocytosis highighted by macrophage specific CD163 staining of the spleen of a patient with HLH. (Photo courtesy of Dr. Russell Ryan)