Virus-associated histiocytic proliferations in children. Frequent association with Epstein-Barr virus and congenital or acquired immunodeficiencies.

Nineteen children who presented with fever, hepato-splenomegaly, bone marrow and/or hepatic failure, and biopsy evidence of histiocytic proliferations were evaluated for lymphocyte dysfunction and evidence of prior viral infection. Seventeen of the children had erythrophagocytosis consistent with the previously described virus-associated hemophagocytosis syndrome (VAHS) or Familial erythrophagocytic lymphohistiocytosis (FEL). The other two had benign histiocytic proliferations in the central nervous system (CNS) with liver and bone marrow dysfunction. There were two sibling pairs and six patients with known disorders of immune deficiency. The remaining nine cases appeared to be sporadic and idiopathic. Epstein-Barr Virus (EBV) was identified in patients by serologic or DNA hybridization studies (15), EBV and cytomegalovirus (CMV) (1), adenovirus plus EBV and CMV (1), or adenovirus and EBV (1). Herpes zoster was associated with reactivation of symptoms in one patient. Immunologic impairment was evidenced by lymphopenia in 10 of 19 patients. More extensive evaluations could be done at diagnosis on only some of the children because the histiocytic proliferative syndrome was not recognized or because there were insufficient numbers of lymphocytes in samples obtained. For those who could be evaluated, the following immune deficiencies were found: decreased lymphocyte proliferation to mitogens (4 of 9), absent or markedly decreased natural killer function (5 of 5), and decreased cytotoxic lymphocyte reactivity to allogenic EBV-infected target cells (3 of 3). A new finding reported here is a higher than expected prevalence of HLA types A30, B8, and A1/B8 among the patients tested.