Hemophagocytic Lymphohistiocytosis (HLH) Diagnosis and Treatment
Clinical Presentation and Diagnosis
- HLH presents with a constellation of hyperinflammatory symptoms that require immediate recognition to prevent mortality from multiorgan failure, according to the American Society of Hematology 1
- Persistent fever unresponsive to antibiotics is a key clinical feature of HLH 2
- Hepatosplenomegaly with liver dysfunction and elevated transaminases is a common presentation of HLH 1
- The diagnosis of HLH requires 5 of 8 HLH-2004 criteria, including fever, splenomegaly, cytopenias, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent NK cell activity, ferritin ≥500 ng/mL, and soluble CD25 ≥2400 U/mL, as recommended by the Histiocyte Society 1
Treatment Approach
- The American College of Physicians recommends treating the underlying trigger aggressively, with antimicrobials for infection-associated HLH, disease-specific therapy for malignancy-associated HLH, and optimizing rheumatologic disease control for MAS-HLH 1
- Corticosteroids, such as dexamethasone or prednisolone, are used as first-line immunosuppression for mild-to-moderate HLH, according to the European Society for Medical Oncology 1
- IVIG may be considered for anti-inflammatory effects in patients with HLH, as suggested by the Infectious Diseases Society of America 1, 4
- Etoposide-based therapy is reserved for patients with severe HLH or imminent organ failure, with a modified HLH-94 protocol, as recommended by the American Society of Hematology 1
Critical Care Management
- Patients requiring ICU admission need aggressive supportive care combined with HLH-directed therapy, with reevaluation at least every 12 hours, according to the Society of Critical Care Medicine 2
- Infection prophylaxis, including pneumocystis jirovecii prophylaxis, antifungal prophylaxis, and antiviral prophylaxis, is essential for patients with HLH, as recommended by the Centers for Disease Control and Prevention 1, 6
Allogeneic Stem Cell Transplantation
- Patients with primary (genetic) HLH require allogeneic SCT for cure after achieving disease control, according to the European Society for Blood and Marrow Transplantation 6, 7
- Reduced-intensity conditioning (RIC) is recommended for primary HLH and nonmalignant secondary HLH, while myeloablative conditioning (MAC) is used for malignancy-associated HLH, as suggested by the American Society for Blood and Marrow Transplantation 6