X-linked lymphoproliferative disease (XLP) is a rare inborn error of immunity (IEI) characterized by increased susceptibility to Epstein–Barr Virus (EBV) and other features of immune dysregulation. We present a case of XLP1, diagnosed in a 37-year-old male with EBV viremia treated with nivolumab.
The proband was diagnosed with common variable immunodeficiency (CVID) and started on IVIG at age 8. Infections were recurrent pneumonias and an episode of septic hip arthritis. He remained infection free over the next 3 decades until presenting with Evans syndrome at age 37, which was initially treated with prednisone. Shortly after, his course was complicated with hepatic and brain abscesses and liver decompensation. Thus, he was referred to our service for workup. Genetic testing revealed the diagnosis of XLP1 (SH2D1A c.138-2A>G).
He was found to have EBV viremia, and a liver biopsy suggested EBV hepatitis. He was not a liver transplant candidate due to concern of sepsis given his immunosuppression and IEI. Hematopoietic stem cell transplant (HSCT) was not offered due to high risk of mortality. Despite treatment with rituximab, his repeat EBV titers continued to rise. Virus-specific T cell therapy was pursued; however, the patient was clinically too unstable to be transferred for treatment to the United States from Canada. He was given one nivolumab dose, significantly reducing his viremia. He ultimately succumbed to sepsis and respiratory failure.
EBV is the leading cause of mortality in patients with XLP who forego HSCT. Rituximab has been well-documented in the treatment of EBV. We present a patient with an EBV susceptibility syndrome and progressive viremia, who responded well to one dose of nivolumab which significantly reduced his EBV viral load. Despite limited literature, nivolumab may play a significant role in the treatment of certain EBV-associated conditions, particularly in patients with IEIs.
In conclusion, nivolumab should be considered for any patient with an overwhelming EBV infection. Severe EBV-induced disease is an unexpected finding in an individual with CVID and warrants genetic testing to exclude other primary immunodeficiencies. Treatment options for EBV susceptibility syndromes need further exploration and accessibility.
