Hypersensitivity to mosquito bites is not an allergic disease, but an Epstein-Barr virus-associated lymphoproliferative disease.

Recently, we showed that 5 cases of hypersensitivity to mosquito bites (HMB) concealed the clonal lymphoproliferation of Epstein-Barr viral (EBV) DNA-positive natural killer (NK) cells. Although the symptoms of HMB have been supposed to derive from Arthus phenomenon, it has become apparent that this unique disorder has the potential to develop into so-called malignant histiocytosis (MH) or related disorders. Accordingly, the criteria for MH have been changed, and a newer diagnostic name, hemophagocytic syndrome, has been described as being associated with viral infection or leukemia/lymphoma. We previously reported that biopsy specimens taken from skin lesions demonstrated infiltration of lymphocytes bearing the phenotype of NK cells. In this study, we found that skin lesions exhibited infiltration of atypical lymphocytes around the small vessels, resembling angiocentric lymphoma, and that these infiltrating cells were positive for EBER-1 by in situ hybridization. These findings support the concept that HMB is the most important manifestation of a certain type of lymphoproliferative disease that presents with an intense local skin reaction and high fever following mosquito bites, and whose essence is the lymphoproliferation of EBV DNA-positive NK cells.