Hydroa vacciniforme–like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites

Abstract

Patients with classic hydroa vacciniforme–like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that whites were less likely to develop systemic EBV disease (1/10) than nonwhites (5/6). All (10/10) of the white patients were generally in good health at last follow-up, while two-thirds (4/6) of the nonwhite patients required hematopoietic stem cell transplantation. Nonwhite patients had later age of onset of HVLPD than white patients (median age, 8 vs 5 years) and higher levels of EBV DNA (median, 1 515 000 vs 250 000 copies/ml) and more often had low numbers of NK cells (83% vs 50% of patients) and T-cell clones in the blood (83% vs 30% of patients). RNA-sequencing analysis of an HVLPD skin lesion in a white patient compared with his normal skin showed increased expression of interferon-γ and chemokines that attract T cells and NK cells. Thus, white patients with HVLPD were less likely to have systemic disease with EBV and had a much better prognosis than nonwhite patients. This trial was registered at www.clinicaltrials.gov as #NCT00369421 and #NCT00032513.

Hydroa vacciniforme-like lymphoproliferative disorder: A study of clinicopathology and whole-exome sequencing in Chinese patients

“…We found that race and the age at onset were correlated with the prognosis of patients with HVLPD, which is consistent with the results reported by Cohen [11]. Compared with the patients in Cohen's study, our patients had a higher tendency to progress to systemic diseases, and their main manifestations were persistent fever and involvement of the lymph nodes, lungs, liver and spleen.…”

“…HVLPD shares many common features with EBV T/NK cell lymphoproliferative diseases or CAEBV without HVLPD, including high levels of EBV DNA in the blood (primarily inTor NK cells) and a high frequency of clonal T cells. However, EBV T/NK cell lymphoproliferative diseases and CAEBV without HVLPD are more fatal [11]. Thus, distinguishing HVLPD from EBV T/NK cell lymphoproliferative diseases or CAEBV without HVLPD is very important.…”

Hydroa Vacciniforme and Hydroa Vacciniforme-like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein-Barr Virus Infection

“…In addition, over 90% of patients with classic HV or atypical/severe HV have elevated γδ T-cell percentages > 5%, and all HV patients have a high EBV DNA load, although there were no statistically significant differences between classic versus atypical/severe HV [35]. By realtime quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry immunophenotypic analysis, Cohen et al described elevated levels of EBV DNA in the blood and high levels of EBV DNA in T or NK cells in all HVLPD patients, without any significant differences between patients with classic versus atypical/severe HV [17]. Compared to classic HV patients, atypical/severe HV patients more frequently had abnormal antibody profiles to EBV antigens, such as elevated antiviral capsid antigen (VCA),elevated anti-early antigen (EA) and low EBV nuclear antigen (EBNA), and the serologic patterns were consistent with chronic active EBV infection [9].…”

Hydroa Vacciniforme-Like Lymphoproliferative Disorder in an Adult Patient With Chronic Lymphocytic Leukemia

“…Classic HV-LPD was originally described in the Caucasian population and is characterized by a photodermatosis originating as vesicles, evolving to crusts and leaving varicelliform scars after healing [1][2][3][4]. Systemic symptoms are usually not observed and this benign condition normally improves with sun avoidance and resolves spontaneously in adolescence [1][2][3][4].…”

“…Systemic hydroa vacciniforme (HV) typically affects children and adolescents from Asia and Latin America [1][2][3][4]. This generally presents as a more severe cutaneous condition; however, systemic features including constitutional symptoms, hepatosplenomegaly and lymphadenopathy are also present.…”