Introduction: Hemophagocytic lymphohistiocytosis (HLH) is caused by an unregulated immunoinflammatory response leading to acute organ failure and even death. It has multiple etiologies such as genetics, autoimmune disorders, malignancy, and viral infections like Epstein-Barr Virus (EBV). Findings include fever, cytopenia in two cell lines, hepatosplenomegaly, hypertriglyceridemia, hemophagocytosis in bone marrow or liver biopsy, low natural killer T-cell (NK) activity, hyperferritinemia, and elevated soluble IL-2 receptor (sIL2r). Diagnosis is made when 5 of the above criteria are met. Identification is key as survival is low even if treated. We present a patient who developed acute liver failure (ALF) from EBV induced HLH.
Case Description/Methods: A 57-year old woman with selective IgA-deficiency (s-IgA-d) presented with malaise, jaundice, and right upper quadrant tenderness. Blood-work revealed leukopenia, thrombocytopenia, cholestasis, and elevated C- reactive protein. Abdominal ultrasound showed a dilated common bile duct without cholelithiasis or choledocholithiasis and MRCP showed hepatosplenomegaly and numerous hepatic cysts. Viral serologies were checked and supportive treatment was started. She reported improvement in symptoms and was discharged but returned 4 days later with fever, vomiting, and encephalopathy. Blood-work revealed anemia, elevated inflammatory markers, decreased synthetic liver function, and acute EBV infection. A diagnosis of ALF secondary to EBV was made. HLH was considered so sIL2r was checked and corticosteroids were started. Levels of sIL2r ultimately came back elevated, confirming the diagnosis. The patient improved and was discharged without complications.
Discussion: HLH is a devastating condition with multiple etiologies and our patient’s s-IgA-d may be relevant. IgA levels were significantly lower in pediatric patients who developed HLH from EBV compared to those who developed Infectious Mononucleosis. The function of serum IgA is not fully known but it inhibits macrophages through an IgA-specific receptor. Lack of inhibition and abnormal signaling from atypical lymphocytes produced by EBV offers a potential mechanism. S-IgA-d is the most common immunodeficiency with a prevalence of 1 in 500. Most are asymptomatic though there is a higher prevalence of autoimmune and allergic disorders in these patients. More research is required as HLH remains a complex syndrome that must be identified before catastrophic tissue destruction occurs.
