Hydroa vacciniforme (HV) is a rare photosensitivity disorder of childhood associated with Epstein-Barr virus (EBV)(+) T-cell infiltration. We have summarized clinical manifestations of HV, and analyzed EBV(+) T-cell subsets as well as EBV DNA load in lymphocyte fractions, in comparison with hypersensitivity to mosquito bites (HMB), an EBV-associated T/natural killer (NK) lymphoproliferative disorder. We found that 31 of 33 (93.9%) HV lesions were composed of EBV(+) T cells and reactive EBV(-) cytotoxic T cells, without significant CD56(+) cell infiltration, whereas many CD56(+) cells were present in 8 of 9 (88.9%) HMB lesions. Of 13 (20.6%) HMB patients with or without HV, 12 (92.3%) showed increased percentages (>32%) of NK cells in the peripheral blood, whereas in the 16 patients with HV alone, 14 (87.5%) showed no increase. Of the 11 HV patients, 10 (90.9%) had increased percentages (>5%) of circulating γδT cells, with a mean value of 15.7 ± 2.9%, and the γδT-cell fractions contained larger amounts of EBV DNA than non-γδT-cell fractions. A triple-labeling method revealed that all three HV patients examined had increased percentages of EBER(+), T-cell receptor (TCR)γδ(+), and TCRαβ(-) cells. Our observations indicate that HV is associated with increased numbers of EBV(+) γδT cells, whereas HMB is associated with EBV(+) NK cells.

Summary Background Epstein‐Barr virus (EBV)‐associated T/natural‐killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors. Objectives To elucidate the prognostic factors of HV and HMB. Methods We studied clinicopathological manifestations, routine laboratory findings, anti‐EBV titres, EBV DNA load and EBV‐encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow‐up. Results The median age of disease onset was 5 years (range 1–74). A follow‐up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem‐cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV‐encoded immediate–early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively). Conclusions No prognostic correlation was observed in EBV‐infected lymphocyte subsets, anti‐EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.

Estrogens stimulate proliferation and differentiation of uterine epithelial cells in vivo. Mitogenic action of estrogens may be mediated by growth factors such as insulin-like growth factor-I (IGF-I). This study was designed to determine whether IGF-I and insulin affect proliferation of uterine epithelial cells obtained from 3- to 4-week-old immature female mice in a serum-free culture system. The epithelial cell number on Day 5 in culture was significantly increased by adding IGF-I (10 and 100 ng/ml) or insulin (100 and 1000 ng/ml) to the culture media, indicating that IGF-I is more effective than insulin in inducing the epithelial growth. The epithelial DNA synthesis was significantly stimulated by IGF-I (1 and 10 ng/ml), suggesting that both the epithelial proliferation and their detachment from substratum are stimulated by 1 ng/ml of IGF-I, but that the former is more accelerated than the latter by 10 ng/ml of IGF-I. These results demonstrate that both IGF-I and insulin directly stimulate the growth of uterine epithelial cells, and suggest that insulin may act via IGF-I receptors. IGF-I immunoreactivity was detected in the cytoplasm of the cultured cells, indicating that the cells synthesize IGF-I. Estradiol-17 beta (E2) at lower concentrations (0.001-0.1 nM) tended to increase the number of epithelial cells, while E2 at higher concentrations (1 to 100 nM) did not affect it. It is highly probable that IGF-I produced in endometrial cells induces their proliferation by an autocrine or paracrine mechanism.