A boy with fever, lymphadenopathy, hepatosplenomegaly, and lymphocytosis

Abstract

Proliferation of the lymphoid system should arouse suspicion of a potentially serious illness. We present a 4.5-year-old boy who developed fever, vomiting, diarrhea, lymphadenopathy, hepatosplenomegaly, lymphocytosis, anemia, thrombocytopenia, and increased liver enzymes. Lymph node and bone marrow biopsies showed lymphoproliferation, Epstein-Barr virus (EBV) infection, and hemophagocytosis leading to the diagnosis of hemophagocytic lymphohistiocytosis (HLH). Chemotherapy was initiated for HLH with dexamethasone, etoposide, and cyclosporine. Because of a high level of EBV viremia, rituximab was added a few days later and resulted in a remarkable drop in the EBV in the circulation but not in the cerebrospinal fluid. However, the patient succumbed to encephalitis, pneumonia, and cardiopulmonary failure. Autopsy revealed the presence of EBV in the brain, indicating the ineffectiveness of rituximab therapy in treating central nervous system infection with EBV.

Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature

“…The utility of biologic agents in the management of this syndrome remains unclear and the reported experience in the literature is anecdotal. These agents include tumour necrosis factor inhibitors like Infliximab [40] and Etanercept [13] and the anti-CD20 monoclonal antibody, rituximab; Rituximab may be of utility in subpopulations where the underlying aetiology is related to EBV infection [41,42]. Daclizumab, a monoclonal anti-CD25 antibody, has been shown in a single case report as being effective in successfully treating steroid-dependant HLH, allowing withdrawal of the steroids without relapse of the syndrome [43].…”

A case of a girl presenting with fever, cytopenia, liver dysfunction, hepatosplenomegaly, and hemophagocytosis in the bone marrow

“…3,8,9,13 In two of these cases, rituximab was used in combination with cytotoxic drugs. 8,9 In both cases clinical improvement coincided with a reduction in the EBV viral load.…”

“…Kaza et al, 13 used rituximab to treat a young boy with EBV-HLH. Initial improvement correlated with a reduction in EBV viral load; however, the child subsequently died of EBV encephalitis.…”

“…3,8,9,12,13 Rituximab is a humanized anti-CD20 monoclonal antibody which targets and depletes mature B cells within 48 h of therapy. In relation to HLH, the inclusion of rituximab may rapidly reduce the numbers of B cells containing EBV; it is these cells that are thought to drive the dysregulation of the inflammatory response.…”

Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis in Los Angeles County

“…To our knowledge, only 13 well‐characterized cases of EBV‐associated HLH have been described in the United States. However, none of these cases described the molecular characteristics of the virus and host associated with the EBV‐HLH phenotype [Quintanilla‐Martinez et al, 2000; Halasa et al, 2003; Lindemann and Greene, 2005; Mischler et al, 2007; Rouphael et al, 2007; Brodkin et al, 2008; Kaza et al, 2008; Belyea et al, 2010]. Although EBV‐HLH is a rare disease, the incidence in adults in the United States may be underestimated.…”