DEXAMETHASONE AND AMPHOTERICIN B TO THE RESCUE: A CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Abstract

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease characterized by immune system overstimulation resulting in widespread inflammation, a cytokine surge, and multisystem organ failure. HLH is associated with significant mortality, so early recognition and a multidisciplinary approach to treatment are key for improved survival. CASE PRESENTATION: A 59-year-old kidney and pancreas transplant recipient presented with diarrhea, fevers, altered mental status, and acute kidney injury. He was transferred to the ICU due to respiratory distress and was started on antibiotics. CT scan of the chest and abdomen showed a small right lower lobe consolidation and mild splenomegaly. Sputum, urine, and blood cultures were negative. Serum fungitell was elevated and Aspergillus galactomannan serum antigen was positive. Serum Histoplasma antigen was >25ng/mL and urine Histoplasma antigen was 7.8ng/mL. Amphotericin B was started and hematology was consulted for presumed HLH secondary to histoplasmosis with elevated ferritin (7559 ng/mL) and triglycerides (227). Bone marrow aspirate demonstrated foamy histocytes and hemophagocytic histiocytes as well dimorphic fungal forms in the interstitium and within a granuloma on GMS stain consistent with Histoplasma. Dexamethasone was initiated at 10mg/m2. Soluble IL-2R was 14,120 U/mL. He clinically improved on dexamethasone and was transitioned from amphotericin to itraconazole. DISCUSSION: At least 5 out of 8 of the following criteria must be met for a diagnosis of HLH: fever, splenomegaly, cytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in bone marrow, spleen or lymph nodes, low/absent NK-cell activity, ferritin ≥ 500 mg/L, and soluble CD25 ≥2400 U/mL. This patient had 6/8 of the diagnostic criteria for HLH: fever, splenomegaly, hypertriglyceridemia, ferritin >500, high soluble IL-2 receptor, and hemophagocytosis in bone marrow. A multidisciplinary discussion involving critical care, hematology, and transplant infectious disease was held about initiating Etoposide due to rising ferritin (based on evidence supporting the use of Etoposide in pediatric patients with HLH), however, data is lacking regarding how to treat adult patients with HLH and histoplasmosis. He was clinically improving without Etoposide and there was concern that Etoposide would make his histoplasmosis more difficult to treat, so he was not given Etoposide. Histoplasma is a known but rare cause of HLH (<50 published cases). Due to the rarity of HLH and its risk for mortality, it is important to have a high index of suspicion to test for HLH in an immunosuppressed patient who presents with fevers. CONCLUSIONS: Working with a multidisciplinary team was essential to both the diagnosis and management of HLH due Histoplasma due to a lack of evidence about optimal treatment. Research is needed to improve outcomes for patients with HLH due to Histoplasma. REFERENCE #1: Hayden, A., Park, S., Giustini, D., Lee, A. Y., & Chen, L. Y. (2016). Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review. Blood reviews, 30(6), 411–420. https://doi.org/10.1016/j.blre.2016.05.001 REFERENCE #2: Bergsten, E., Horne, A., Aricó, M., Astigarraga, I., Egeler, R. M., Filipovich, A. H., Ishii, E., Janka, G., Ladisch, S., Lehmberg, K., McClain, K. L., Minkov, M., Montgomery, S., Nanduri, V., Rosso, D., & Henter, J. I. (2017). Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood, 130(25), 2728–2738. https://doi.org/10.1182/blood-2017-06-788349 REFERENCE #3: Filipovich A. H. (2009). Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology. American Society of Hematology. Education Program, 127–131. https://doi.org/10.1182/asheducation-2009.1.127 DISCLOSURES: No relevant relationships by Maureen McElligott, source=Web Response No relevant relationships by Meilinh Thi, source=Web Response