{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:16Z","timestamp":1787028436553,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein\u2013Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.<\/jats:p>","DOI":"10.3390\/ijms21239314","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T12:24:39Z","timestamp":1607343879000},"page":"9314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hydroa Vacciniforme and Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein\u2013Barr Virus Infection"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-0884","authenticated-orcid":false,"given":"Chien-Chin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan"},{"name":"Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan"},{"name":"Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kung-Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L Jeffrey","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Yu-Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"ref_1","first-page":"132","article-title":"Lecons theoriques et cliniques sur les affectations generiques de la peau","volume":"1","author":"Bazin","year":"1862","journal-title":"Delabrage"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1365-2133.2009.09451.x","article-title":"Photodermatoses: Classification, evaluation and management","volume":"161","author":"Bylaite","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13030\/qt1rx7d228","DOI":"10.5070\/D3222030080","article-title":"Update on treatment of photodermatosis","volume":"22","author":"Gozali","year":"2016","journal-title":"Dermatol. Online J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1001\/archderm.1978.01640200047012","article-title":"Hydroa vacciniforme","volume":"114","author":"Bickers","year":"1978","journal-title":"Arch. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.4997\/jrcpe.2017.408","article-title":"A review of photodiagnostic investigations over 26 years: Experience of the national Scottish photobiology service (1989\u20132015)","volume":"47","author":"Nassan","year":"2017","journal-title":"J. R. Coll. Physicians Edinb."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/phpp.12543","article-title":"Comparison of racial distribution of photodermatoses in USA academic dermatology clinics: A multicenter retrospective analysis of 1080 patients over a 10-year period","volume":"36","author":"Hamel","year":"2020","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0190-9622(00)90127-0","article-title":"Hydroa vacciniforme: A clinical and follow-up study of 17 cases","volume":"42","author":"Gupta","year":"2000","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1001\/archderm.1986.01660230102021","article-title":"Hydroa vacciniforme: Diagnosis by repetitive ultraviolet-A phototesting","volume":"122","author":"Eramo","year":"1986","journal-title":"Arch. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1001\/archderm.142.5.587","article-title":"Pathogenic link between hydroa vacciniforme and Epstein-Barr virus-associated hematologic disorders","volume":"142","author":"Iwatsuki","year":"2006","journal-title":"Arch. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1111\/cup.12801","article-title":"Hydroa vacciniforme and hydroa vacciniforme-like T-cell lymphoma: An uncommon event for transformation","volume":"43","author":"Chen","year":"2016","journal-title":"J. Cutan. Pathol."},{"key":"ref_11","unstructured":"Swerdlow, S.H., and Campo, E. (2008). EBV positive T cell lymphoproliferative disorders of childhood. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press. [4th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_13","unstructured":"Swerdlow, S.H., and Campo, E. (2017). Hydroa vacciniforme-like lymphoproliferative disorder. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press. [4th ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/DAD.0000000000001229","article-title":"Comparative study of the clinical pathology, immunophenotype, Epstein-Barr virus infection status, and gene rearrangements in adult and child patients with hydroa vacciniforme-like lymphoproliferative disorder","volume":"41","author":"Wen","year":"2019","journal-title":"Am. J. Dermatopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/DAD.0000000000000385","article-title":"Clinicopathologic features of hydroa vacciniforme-like lymphoma: A series of 9 patients","volume":"38","author":"Massone","year":"2016","journal-title":"Am. J. Dermatopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1525-1470.2010.01094.x","article-title":"Epstein-Barr virus-associated hydroa vacciniforme-like cutaneous lymphoma in seven Chinese children","volume":"27","author":"Xu","year":"2010","journal-title":"Pediatr. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1182\/blood.2018893750","article-title":"Hydroa vacciniforme-like lymphoproliferative disorder: An EBV disease with a low risk to systemic illness in Caucasians","volume":"133","author":"Cohen","year":"2019","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1365-2133.2010.09789.x","article-title":"Epstein-Barr virus involvement in the pathogenesis of hydroa vacciniforme: An assessment of seven adult patients with long-term follow-up","volume":"163","author":"Verneuil","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.jaad.2019.01.011","article-title":"Hydroa vacciniforme-like lymphoproliferative disorder: Clinicopathologic study of 41 cases","volume":"81","author":"Liu","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1182\/blood-2013-05-502203","article-title":"Hydroa vacciniforme-like lymphoma: A chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma","volume":"122","author":"Ridaura","year":"2013","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575120","DOI":"10.5402\/2012\/575120","article-title":"Cutaneous T-cell lymphoma in Asians","volume":"2012","author":"Jang","year":"2012","journal-title":"ISRN. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.dsi.2017.08.004","article-title":"Cutaneous lymphomas in Taiwan: A review of 118 cases from a medical center in southern Taiwan","volume":"36","author":"Lee","year":"2018","journal-title":"Dermatol. Sin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3389\/fmicb.2016.01235","article-title":"The skin microbiome: Is it affected by UV-induced immune suppression?","volume":"7","author":"Patra","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3389\/fmed.2018.00166","article-title":"A perspective on the interplay of ultraviolet-radiation, skin microbiome and skin resident memory TCR\u03b1\u03b2+ Cells","volume":"5","author":"Patra","year":"2018","journal-title":"Front. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1001\/archderm.1982.01650200056017","article-title":"Hydroa vacciniforme: Diagnosis and therapy","volume":"118","author":"Goldgeier","year":"1982","journal-title":"Arch. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0190-9622(83)70019-8","article-title":"Hydroa vacciniforme: Induction of lesions with ultraviolet A","volume":"8","author":"Halasz","year":"1983","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0190-9622(91)70215-N","article-title":"Hydroa vacciniforme with unusually severe scar formation: Diagnosis by repetitive UVA phototesting","volume":"25","author":"Hann","year":"1991","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_28","first-page":"E796","article-title":"Hydroa vacciniforme","volume":"182","author":"Balestri","year":"2010","journal-title":"C.M.A.J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s40257-018-0365-6","article-title":"Recent developments in the diagnosis and management of photosensitive disorders","volume":"19","author":"Nahhas","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41579-019-0249-7","article-title":"Latency and lytic replication in Epstein-Barr virus-associated oncogenesis","volume":"17","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fped.2019.00071","article-title":"Epstein-Barr Virus-associated T and NK-cell lymphoproliferative diseases","volume":"7","author":"Kim","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1146\/annurev.immunol.25.022106.141553","article-title":"Cellular responses to viral infection in humans: Lessons from Epstein-Barr virus","volume":"25","author":"Hislop","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cao, P., Zhang, M., Wang, L., Sai, B., Tang, J., Luo, Z., Shuai, C., Zhang, L., Li, Z., and Wang, Y. (2018). miR-18a reactivates the Epstein-Barr virus through defective DNA damage response and promotes genomic instability in EBV-associated lymphomas. BMC. Cancer, 18.","DOI":"10.1186\/s12885-018-5205-9"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1046\/j.1365-2133.1999.02777.x","article-title":"The association of latent Epstein-Barr virus infection with hydroa vacciniforme","volume":"140","author":"Iwatsuki","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/bjd.13411","article-title":"Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites","volume":"172","author":"Miyake","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1002\/jmv.25811","article-title":"The aim of the measurement of Epstein-Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites","volume":"92","author":"Miyake","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1053\/j.semdp.2016.11.003","article-title":"Cutaneous EBV-related lymphoproliferative disorders","volume":"34","author":"Gru","year":"2017","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1182\/blood-2011-10-381921","article-title":"EBV-associated T\/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: Prospective analysis of 108 cases","volume":"119","author":"Kimura","year":"2012","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s13671-019-0255-z","article-title":"Actinic prurigo and hydroa vacciniforme","volume":"8","author":"Adler","year":"2019","journal-title":"Curr. Derm. Rep."},{"key":"ref_40","first-page":"135","article-title":"Photodermatoses: Diagnosis and treatment","volume":"108","author":"Lehmann","year":"2011","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.det.2019.08.007","article-title":"Phototherapy in the evaluation and management of photodermatoses","volume":"38","author":"Jiang","year":"2020","journal-title":"Dermatol. Clin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1365-2133.1988.tb01757.x","article-title":"Hydroa vacciniforme: A review of ten cases","volume":"118","author":"Sonnex","year":"1988","journal-title":"Br. J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1600-0781.1997.tb00124.x","article-title":"Factors influencing the photo-reproduction of hydroa vacciniforme lesions","volume":"13","author":"Leroy","year":"1997","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e290","DOI":"10.1111\/ijd.14931","article-title":"Hydroa vacciniforme-like lymphoproliferative disorder: A retrospective cohort study of seven pediatric cases","volume":"59","author":"Ren","year":"2020","journal-title":"Int. J. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jdermsci.2020.06.013","article-title":"Hydroa vacciniforme-like lymphoproliferative disorder: A study of clinicopathology and whole-exome sequencing in Chinese patients","volume":"99","author":"Xie","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.pathol.2019.09.011","article-title":"Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: An update and diagnostic approach","volume":"52","author":"Hue","year":"2020","journal-title":"Pathology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1046\/j.1365-2141.2003.04359.x","article-title":"Common cytological and cytogenetic features of Epstein-Barr virus (EBV)-positive natural killer (NK) cells and cell lines derived from patients with nasal T\/NK-cell lymphomas, chronic active EBV infection and hydroa vacciniforme-like eruptions","volume":"121","author":"Zhang","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/cid\/ciw160","article-title":"Association of GATA2 deficiency with severe primary Epstein-Barr virus (EBV) infection and EBV-associated cancers","volume":"63","author":"Cohen","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pahlow Mose, A., Fisker, N., Clemmensen, O., and Bygum, A. (2014). Antiviral treatment of a boy with EBV-associated hydroa vacciniforme. BMJ. Case. Rep., 2014.","DOI":"10.1136\/bcr-2014-206488"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"493","DOI":"10.4103\/ijd.IJD_178_18","article-title":"Hydroa vacciniforme-like lymphoma with systemic symptoms: Two case reports","volume":"64","author":"Wang","year":"2019","journal-title":"Indian J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1002\/ajh.23843","article-title":"Thalidomide for the treatment of hydroa vacciniforme-like lymphoma: Report of four pediatric cases from Peru","volume":"89","author":"Maza","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"adv00192","DOI":"10.2340\/00015555-3556","article-title":"Hydroa Vacciniforme-like lymphoproliferative disorder treated with intravenous immunoglobulin: Long-term remission without haematopoietic stem cell transplantation or chemotherapy","volume":"100","author":"Ruan","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13000-019-0859-4","article-title":"Clinicopathological categorization of hydroa vacciniforme-like lymphoproliferative disorder: An analysis of prognostic implications and treatment based on 19 cases","volume":"14","author":"Guo","year":"2019","journal-title":"Diagn. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00129039-200203000-00002","article-title":"Hydroa-like cutaneous T-cell lymphoma: A clinicopathologic and molecular genetic study of 16 pediatric cases from Peru","volume":"10","author":"Barrionuevo","year":"2002","journal-title":"Appl. Immunohistochem. Mol. Morphol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:41:46Z","timestamp":1760179306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,7]]},"references-count":54,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21239314"],"URL":"https:\/\/doi.org\/10.3390\/ijms21239314","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202010.0223.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,7]]}}}