Immunological Warfare: Two Cases of Hemophagocytic Lymphohistiocytosis in Young Adults

Ryan Sugarman, MD; Yonatan Greenstein, MD; Seth Koenig, MD

INTRODUCTION: Hemophagocytic lymphohistiocystosis (HLH), a syndrome of pathologic immune system activation, results in a severe systemic inflammatory response. Rare in adults, it is well-described in the pediatric population. If unrecognized it is uniformly fatal; with prompt treatment mortality remains high. We present two cases of Epstein-Barr virus (EBV) associated HLH in young adults admitted to the medical intensive care unit (MICU).

CASE PRESENTATION: Case 1 was a 20 year old male college student diagnosed with infectious mononucleosis (IM) three weeks prior. Presenting complaints were fevers, night sweats, and emesis. He was in presumed septic shock with multiorgan failure and was admitted to the MICU. Vasopressors and antibiotics were initiated and he was intubated after a seizure. Hemodialysis (HD) was begun due to renal failure. Due to worsening cytopenias and recent diagnosis of EBV, HLH was considered. He met six of eight diagnostic criteria for HLH (Table 1) and was started on chemotherapy with etoposide, rituximab, and dexamethasone.1 Intrathecal methotrexate and hydrocortisone were given; he later required salvage therapy with alemtuzumab. He was discharged home 38 days later. Case 2 was an 18 year old female college student with a history of asthma who was diagnosed with IM one month prior. She presented with respiratory failure requiring mechanical ventilation and multiorgan failure from presumed sepsis. Baseline admission vital signs and laboratory values are shown for both patients (Table 2). Treatment with antibiotics, N-acetylcysteine for severe transaminitis, and HD were begun. Due to recent EBV infection and cytopenias, HLH was considered. She met all diagnostic criteria for HLH and was started on etoposide, rituximab, and dexamethasone. On hospital day ten she developed refractory hypercapnic respiratory failure secondary to severe involvement of her tracheobronchial tree due to invasive aspergillosis. Despite antifungal and chemotherapy she died on day 13.

DISCUSSION: Likely under diagnosed due to nonspecific criteria, the adult intensivist should be on the lookout for HLH. Both patients had a recent EBV infection which is the most frequent infection associated with HLH2. Bone marrow biopsy of both patients demonstrated hemophagocytosis. Both patients were treated according to HLH-2004 guidelines which reported a 65% 3-year survival.1 Rituximab was given for its action against B cells which act as a reservoir for EBV. Survivors of HLH should have an analysis for gene mutations in key proteins involved in immune function, as bone marrow transplantation (BMT) may be lifesaving.3 The patient from case 1 was found to have a perforin mutation and is being evaluated for BMT.

CONCLUSIONS: A high degree of suspicion is required for the diagnosis of HLH. A favorable outcome requires prompt diagnosis and initiation of chemotherapy.

Chest. 2014;146(4_MeetingAbstracts):297A. doi:10.1378/chest.1988646