Hypersensitivity to mosquito bites with natural-killer cell lymphocytosis: The possible implication of Epstein-Barr virus reactivation

Hypersensitivity to mosquito bites (HMB) has been recognized as one of the wide variety of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders, some of which overlap with chronic active EBV infection and hydroa vacciniforme. It frequently predisposes to hemophagocytic syndrome or lymphoid malignancy with a clonal EBV replication. Here we report an 8-year-old Japanese boy who presented with a 3-year history of HMB. Every summer, he had repeated severe local skin reactions with high-grade fever, lymphadenopathy, and mild liver dysfunction after mosquito bites. Histologically, lymphoid cells overexpressing EBV-encoded small nuclear RNAs (EBER), a marker of latent EBV infection, and eosinophils infiltrated diffusely into the lesional skin. His blood tests showed a marked increase in the CD11b⁺ 16⁺ 56⁺ natural-killer cell population (∼ 50% of the peripheral lymphocytes), but neither a clonal proliferation of EBV nor abnormal antibody titers to EBV. Quantitative PCR using a cloned EBV-determined nuclear antigen (EBNA)-1 vector revealed that a high copy number of the EBV genome is integrated into his peripheral blood cells even during the mosquito-free winter. Based on this evidence, he was diagnosed as being in a smoldering stage of HMB, in which EBV-associated NK cell lymphoproliferation might participate in its pathogenesis.