A young boy, born in 2004, without any significant medical or surgical history complained of an itchy neck since some months. Dermatological examination revealed small hyperkeratotic itchy lesions, sometimes isolated, sometimes more confluent. Physical examination was without particularities. A differential diagnosis of a lichen planus, lichen striatus, epidermal hamartoma, Darier’s dyskeratoma, Grover’s disease was proposed. A skin biopsy revealed epidermodysplasia verruciformis of Lutz-Lewandowsky (Orphanet number 302) (EV).
EV is a rare genodermatosis linked to inactivating PH mutations in the EVER1 and EVER2 genes, which are located adjacent to one another on chromosome 17. These genes play a role in the regulation and homeostasis of the Zn distribution in the cell nucleus.
Several homozygous inactivating mutations can be observed in these genes : EVER 1 (TMC6): 7 mutations and EVER 2 (TMC8): 5 mutations. These mutations lead to an extensive beta Papillomavirus replication and proliferation. Among the HPV viruses retrieved in EV patients one may encounter : 5, 8, 9, 12, 14, 15, 16, 17, 19, 20/46, 21, 22, 23, 24, 25, 36, 37, 38, 47, 49, 50, 75, 80, 92, 93, 96 and 107.
The danger is the malignant transformation and numerous squamous cell carcinomas that may finally be lethal. Merkel cell carcinoma and sebaceous carcinoma may also be observed.
Other acquired forms of EV have to be excluded, in particular during HIV, organ transplantation, pCNKTCL and myelodysplastic syndrom.
Topical treatment may include imiquimod, PDT and mebutate ingenol. Systemic treatments include retinoids and cidofovir. Although there are no vaccination recommendations it seems logical to propose the nonavalent antiHPV vaccin in order to stimulate (booster type) the anti-HPV immunity.
References:
Burger B, Itin PH. Epidermodysplasia verruciformis. Curr Probl Dermatol 2014;45:123-31.
Zampetti A, Giurdanella F, Manco S, Linder D, Gnarra M, Guerriero G, Feliciani C. Acquired epidermodysplasia verruciformis: a comprehensive review and a proposal for treatment. Dermatol Surg 2013;39:974-80.
Patel T, Morrison LK, Rady P, Tyring S. Epidermodysplasia verruciformis and susceptibility to HPV. Dis Markers 2010;29:199-206. Przybyszewska J, Zlotogorski A, Ramot Y. Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate. J Am Acad Dermatol 2017 Feb 10. pii: S0190-9622(16)31296-8
G. Absil1, MD; N. Nikkels-Tassoudji1, MD; J.E. Arrese2, MD, PhD; B. Dezfoulian1 MD; PhD, AF. Nikkels1 MD, PhD.
Departments of Dermatology1 and Dermatopathology2, CHU du Sart Tilman, University of Liège, Liège, B-4000 BELGIUM