Hemophagocytic lymphohistiocytosis (HLH) is an aggressive, life-threatening syndrome of excessive immune activation. Prompt initiation of treatment for HLH is essential for the survival of affected patients.
The treatment and prognosis of patients with HLH and the macrophage activation syndrome (MAS), a form of HLH in patients with juvenile idiopathic arthritis and other rheumatologic conditions, will be discussed here. The genetics, clinical features, and diagnosis of HLH are presented separately. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis".)
OVERVIEW AND INDICATIONS FOR TREATMENT
Hemophagocytic lymphohistiocytosis (HLH) is a progressive syndrome of unchecked immune activation and tissue damage. If left untreated, patients with HLH survive for only a few months, due to progressive multi-organ failure. In 1994, the Histiocyte Society organized the first treatment protocol for HLH (HLH-94), which dramatically increased this survival rate to 54 percent with a median follow-up of six years [1,2].
Often, the greatest barrier to treatment and a successful outcome for individuals with HLH is a delay in diagnosis. Several aspects of the clinical presentation of HLH contribute to this delay, including the rarity of the syndrome, the variable clinical presentation, and the lack of specificity of the clinical and laboratory findings. Diagnostic criteria for HLH are based upon those used in the major HLH studies, and therefore may be too stringent to capture all patients with HLH. Thus, treatment is appropriate for some who do not meet the strict diagnostic criteria but for whom there is a high degree of clinical suspicion for HLH. Any patient with suspected HLH should be seen by a hematologist, and those who are acutely ill should be transferred emergently to a facility where they can receive HLH therapy. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Evaluation and diagnostic testing' and 'Hematologist referral and pretreatment testing' below.)
The goal of therapy for patients with HLH is to suppress life-threatening inflammation by destroying immune cells. Induction therapy based on the HLH-94 protocol consists of a series of weekly treatments with dexamethasone and etoposide (VP-16), followed by cyclosporin. Intrathecal methotrexate is given to those with central nervous system disease. After induction, patients who are recovering are weaned off therapy, while those who are not improving are continued on therapy as a bridge to allogeneic hematopoietic cell transplantation (HCT). HCT will likely also be required in those with an HLH gene mutation and/or central nervous system disease.