PC1203: Epstein-barr Virus Associated Hemophagocytic Lymphohistiocytosis Successfully Treated with Anakinra

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe life threatening hyperinflammatory condition. Treatment of HLH has traditionally included etoposide-based regimens, despite potential side effects. This report highlights a case of Epstein Barr virus (EBV) associated HLH successfully treated with anakinra.

Case Description: A 17-year-old male presented to the emergency room with one week of headache, arthralgia, and generalized fatigue. His physical exam revealed a temperature of 39.2℃, conjunctival injection and cervical lymphadenopathy. Laboratory workup revealed thrombocytopenia (70,000/µL), transaminitis ALT 230 U/L, AST 221 U/L, LDH 965 u/L, elevated ferritin 8000 microgram/L, and CRP 230 mg/L. Infectious workup was notable for positive EBV IgM, negative IgG, with an elevated EBV viral load via PCR. The markedly elevated ferritin was concerning for HLH and subsequent testing revealed a markedly elevated soluble CD25 (soluble IL-2 receptor alpha) of 9576 pg/mL. Bone marrow biopsy revealed hemophagocytosis. A diagnosis of HLH secondary to EBV infection was made. He was promptly treated with high dose anakinra 100mg every six hours and pulse dose IV methylprednisolone. His fevers and lab derangements responded briskly. He was able to be weaned off of anakinra and be discharged home after seven days on a tapering dose of prednisone with no recurrence of HLH to date. Genetic testing for HLH associated mutations was negative.

Discussion: HLH is an aggressive and life-threatening disease that is characterized by excessive immune activation and uncontrolled inflammation. Some cases have genetic association (mostly seen in infancy), and other cases are sporadic, triggered by infections, rheumatologic disorders, immunodeficiencies, or malignancy.

HLH is often under-diagnosed and almost certainly fatal if left without treatment. Treatment regimens are still largely based on HLH-2004 protocol centered on dexamethasone, etoposide, and intrathecal methotrexate (If associated with neurologic symptoms). This regimen has considerable potential treatment-related toxicity including secondary infections, myelotoxicity, liver dysfunction, and secondary malignancies.

Only a handful of prior cases of EBV associated HLH treated with anakinra have been reported in the literature. Anakinra is a recombinant human interleukin 1 (IL-1) receptor antagonist. IL-1 which plays a major role in cytokine storm, among other cytokines, that initiate and perpetuate the inflammatory cascade leading to end organ damage. The IL-1 blockade provides potential for a safer, more targeted treatment approach to HLH.

Anakinra has a long history of safety with its use in rheumatic disease and more recently Multisystem Inflammatory Syndrome in Children (MIS-C). The most common side effect is injection site discomfort. Rarely, opportunistic infections and allergic reactions can occur. Mortality benefit has been shown in HLH patients treated with Anakinra compared to etoposide.

Conclusion: HLH and its traditional chemotherapy-based regimen is associated with significant morbidity and mortality. This case report provides additional support for the efficacy and safety of anakinra in the context of EBV associated HLH.