P0866 - A Case of H1N1 Influenza A-Associated Hemophagocytic Lymphohistiocytosis

Introduction
Hemophagocytic Lymphohistiocytosis (HLH) is an uncommon disease, familial or acquired in etiology, characterized by a robust immune activation secondary to abnormal activation of macrophages and lymphocytes. Unregulated natural killer cells and cytotoxic lymphocytes, unable to clear activated macrophages, lead to overexpression of interferon gamma, resulting in activated macrophages resulting in hemophagocytosis. The upregulation of various pro-inflammatory molecules results in a cytokine storm, which has been linked to high mortality in HLH, resulting from multiorgan failure in various cases. As per HLH-2004 diagnostic criteria, diagnosis must have a molecular diagnosis or have five of the following criteria: fever, splenomegaly, cytopenias (at least two cell lines), hypertriglyceridemia, hemophagocytosis in bone marrow, low/absent NK cell activity, ferritin >500 ng/mL, and elevated sCD25.

Associations between HLH and viruses have been widely established, most commonly with EBV and CMV. The association between HLH and H1N1 influenza A infection has been rarely reported, primarily in adult populations. We present a case of HLH with concomitant H1N1 influenza A infection in a previously healthy 17-year-old patient.

History of Presenting Illness
A 17-year-old female presented with four weeks of intermittent fevers, transaminitis and anemia. On admission, she was also found to have an elevated LDH. Physical exam was significant for hepatomegaly and submandibular lymphadenopathy. Extensive infectious work up was negative including EBV, CMV, Histoplasma, Bartonella and Hepatitis titers. On hospital day 3, she developed fever, myalgias, and respiratory pathogen panel was positive for H1N1 Influenza A. Her condition continued to worsen and on hospital day 7, she had fever, leukopenia, anemia, hypertriglyceridemia, and worsening lymphadenopathy.

HLH diagnosis was explored revealing elevated ferritin, triglycerides and soluble IL-2 receptor while NK function was decreased, and bone marrow biopsy showed macrophages phagocytizing blood. An 8-week steroid taper was started, and she immediately began to show improvement with down-trending fevers, transaminitis, LDH and ferritin levels. Patient was safely discharged home with close follow up.

Discussion & Conclusion
HLH in our patient was likely a result of H1N1 influenza, an underreported association in the pediatric population. A complete infectious workup was performed, and only H1N1 influenza was positive. Interestingly, a 2-year-old male patient in our hospital was treated shortly after, who also tested positive for H1N1 influenza with elevated LDH. The diagnosis of HLH was made shortly after admission due to our recent experience with our case patient.

HLH is rare, diagnosed in approximately 1 in every 3000 patients admitted to tertiary pediatric hospitals. Commonly, diagnosis is delayed resulting in serious sequelae. We believe it is important for pediatric clinicians to be increasingly aware of this association, and consider evaluation, when appropriate, to prevent more serious complications that can occur from delay in diagnosis.