Meet the expert: microbiology case presentation severe EBV infection in a 22-year-old male

Abstract

A 22-year-old male with a history of Type 1 diabetes was admitted to a local hospital in March of this year with generalised malaise and headache. He was noted to have a mild transaminitis, and variant lymphocytes in his blood film. A Monospot test performed at the time was negative. A lumbar puncture was also entirely normal, and he was diagnosed with an unspecified viral illness, and discharged. He re-presented to hospital in early August with a history of headache, fever, dyspnoea and abdominal pain. He was found to have diffuse lymphadenopathy, and massive hepatosplenomegaly. He had variant lymphocytes, thrombocytopenia and severe hepatitis. A mononucleosis screen was positive, and his Epstein-Barr virus (EBV) serology was consistent with primary infection. He had multi-organ failure requiring ventilatory support, vasopressors, continuous haemofiltration, and had marked cholestatic liver function tests. Initial plasma EBV DNA PCR demonstrated 710 000 copies/mL. Testing for cytomegalovirus (CMV) and human herpes virus-6 (HHV-6) was negative. After correction of his coagulopathy and thrombocytopenia, a lymph node biopsy was performed; this showed reactive changes consistent with infectious mononucleosis lymphadenitis, and some evidence of haemophagocytosis. After discussion, it was decided that there were no features of lymphoma on the biopsy. Initial genetic testing for X-linked immunodeficiency was negative. A working diagnosis of EBV-associated haemophagocytic syndrome was made, and he was commenced on cyclosporine, etoposide and hydro-cortisone. Over the next fortnight, his EBV levels reduced slightly, he was able to maintain his own ventilation, and his hepatic function improved, although he remained in anuric renal failure, and was still profoundly pancytopenic. He was discharged to the ward, but developed a severe nosocomial pneumonia with a marked deterioration in his hepatic function. His bilirubin level was elevated at over 400 μmol/L, and he developed intractable seizures secondary to encephalopathy. Six weeks into his hospital admission he died. A post-mortem revealed haemophagocytosis in multiple organs, with high EBV levels throughout the body. Further results of testing for additional primary immunodeficiency disorders are pending. This case raised several issues for us: • spectrum of EBV infections and review of previous cases of fulminant EBV infection at our institution; • histological similarities between EBV lymphadenitis and lymphoma; • pathophysiology and treatment of haemophagocytic syndrome; • association of haemophagocytic syndrome with certain infections.