Hereditary and acquired hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory/hypercytokinemia syndrome clinicopathologically manifested by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hemophagocytosis.

We searched the medical literature for English-written articles and analyzed data regarding the diagnosis, pathoetiology, prognosis, and management of HLH.

HLH can be subcategorized into primary/genetic (PHLH) or secondary/acquired (SHLH) according to etiology. PHLH, including familial HLH and inherited immune deficiency syndromes, typically occurs in children harboring underlying genetic defects, whereas SHLH frequently manifests in adults and is associated with infection, autoimmunity, immune suppression, or malignancy. The pathogenesis of HLH is still elusive. Its known mechanisms include somatic mutations in gene coding for proteins implicated in the cytotoxic pathways of cytotoxic T or natural killer cells. The impaired ability of these cells to kill target cells leads to an uncontrolled hypercytokinemia and hyperinflammatory process, triggering hemophagocytosis and multiorgan failure. Corticosteroids, chemotherapy, and immunotherapy are the mainstay therapeutic strategies. The consolidation with allogeneic hematopoietic stem cell transplantation is a potentially curative option for PHLH and refractory or relapsed SHLH.

Understanding of the pathophysiology of HLH has improved in the last decade. The establishment of diagnostic and treatment guidelines for PHLH and SHLH has resulted in earlier diagnoses and the rapid initiation of therapy, both of which are associated with favorable outcomes.