Hemophagocytic Lymphohistiocytosis in Adults: Updates in Diagnosis and Treatment

Abstract 5037

Hemophagocytic lymphohistiocytosis (HLH) is rare potentially life-threatening disorder that must be recognized and treated early to improve clinical response rates and outcomes. We describe a 36 year-old male with a longstanding history of ulcerative colitis who presented with a one-week history of lymphadenopathy, splenomegaly, fevers, and chills. Workup at an outside institution had been intensive - he had a long complicated hospital course that included hypoxemic respiratory failure requiring intubation and mechanical ventilation, acute kidney injury, hyperbilirubinemia, pancytopenia, coagulopathy, hypofibrinogenemia, CMV viremia, and Clostridium difficile colitis for which he was treated. At our facility, the patient presented with a white blood count of 0.19 10⁹/L (N: 5%, L: 95%, M: 0%, E: 0%, B: 0%), hemoglobin 9.0 mg/L, platelets 54 x10⁹/L, ferritin 538 ng/dL, and triglycerides of 280 mg/dL. A bone marrow biopsy revealed CMV positivity by immunohistochemistry and marked hemophagocytic histiocytosis. The patient was treated with the HLH-2004 chemo-immunotherapy protocol with dexamethasone, etoposide (VP-16), and cyclosporine A. He responded well and is now eight months status-post initial treatment.

HLH in adults is a disorder that little is known about. Acquired forms of HLH can occur in otherwise healthy adults, whereas in children, HLH often presents in its inherited (familial) form. In adults it is often associated with infections (i.e. Epstein-Barr virus, herpes simplex, cytomegalovirus), rheumatologic diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, adult onset systemic Still's disease), malignancy (i.e. natural killer cell leukemia, peripheral T-cell lymphoma, EBV in T-cell lymphoma, B-cell lymphoma, and a variety of other lymphomas). HLH in adults is characterized by cytokine dysfunction and results in the systemic accumulation of activated T-lymphocytes and activated histiocytes (macrophages). Natural killer (NK)-cell and cytotoxic T cell activity in HLH patients is commonly depressed. The standard chemo-immunotherapy protocol as recommended by the Histiocyte Society (HLH-2004) includes therapy with dexamethasone, etoposide (VP-16), cyclosporine A upfront and, in selected patients, cortiocosteriods and intrathecal methotrexate. Thus, early recognition and treatment of this disorder is essential to decrease associated morbidity/mortality. Hemophagocytic lymphohistiocytosis in adults is a diagnosis that must be in the differential whenever a patient presents with fever, cytopenia, hepatosplenomegaly, hypertriglyceridemia and/or hypofibrinogenemia.