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

• Published in: Blood 2019-06, Vol.133 (26), p.2753-2764
• Main Authors: Cohen, Jeffrey I., Manoli, Irini, Dowdell, Kennichi, Krogmann, Tammy A., Tamura, Deborah, Radecki, Pierce, Bu, Wei, Turk, Siu-Ping, Liepshutz, Kelly, Hornung, Ronald L., Fassihi, Hiva, Sarkany, Robert P., Bonnycastle, Lori L., Chines, Peter S., Swift, Amy J., Myers, Timothy G., Levoska, Melissa A., DiGiovanna, John J., Collins, Francis S., Kraemer, Kenneth H., Pittaluga, Stefania, Jaffe, Elaine S.
• Format: Article
• Language: English
• Subjects: Child; Child, Preschool; Epstein-Barr Virus Infections - ethnology; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - pathology; Female; Humans; Hydroa Vacciniforme - virology; Lymphoid Neoplasia; Lymphoproliferative Disorders - ethnology; Lymphoproliferative Disorders - pathology; Lymphoproliferative Disorders - virology; Male; White People
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2018893750

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. •White patients with HVLPD more often had earlier-onset disease, lower EBV DNA, and normal numbers of NK cells in the blood than nonwhites.•White patients with HVLPD were less likely to develop systemic disease or require hematopoietic stem cell transplant than nonwhites. [Display omitted]