Hydroa vacciniforme and hydroa vacciniforme-like lymphoproliferative disorder: Disease spectrum, responsible T-cell subsets and prognosis

Abstract

Hydroa vacciniforme (HV) is a cutaneous subset of Epstein-Barr virus (EBV)-associated T/NK lymphoproliferative disorders (LPDs). Through our case series study of 31 patients with HV, HV-like LPDs and related diseases, we attempted to elucidate the disease spectrum, T-cell subsets responsible for each clinical subtype, and prognoses. Our results clarified a clinical spectrum of EBV-associated T/NK LPDs, which included HV, hypersensitivity to mosquito bites (HMB), chronic active EBV infection (CAEBV), and hemophagocytic lymphohistiocytosis (HLH). Patients with HV are divided into two groups: a benign subtype designated classic HV (cHV), and more serious systemic HV (sHV), also called HV-like LPD in the 2017 WHO classification. Patients with cHV usually have increased percentages of EBV-infected γδT cells, and patients with sHV without HMB are further classified into two groups: γδT-cell- and αβT-cell-dominant types. Patients with HMB, with or without HV-like eruptions, have increased numbers of EBV-infected NK cells in the blood. Patients with cHV and γδT-cell-dominant sHV show a favorable prognosis, but the other subtypes such as αβT-cell-dominant sHV and NK-cell-dominant HMB have a poor prognosis: mortality rates of 11.5 and 3.51 in 100 person-years, respectively. Based on the observations of our case series, we confirmed the poor prognostic indicators as follows: 1) the sHV and HMB clinical subtypes, 2) onset age over 9 years, 3) expression of the reactivation marker, BZLF1 mRNA, and 4) αβT-cell-dominant sHV and NK-cell-dominant HMB. No prognostic correlation was observed in anti-EBV antibody titers or EBV DNA load. From a therapeutic view point, we should exclude the benign subtypes such as patients with cHV and γδT-cell-dominant sHV from the other clinical subtypes.