Epidermodysplasia verruciformis

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Epidermodysplasia verruciformis

Slawomir Majewski and Stefania Jablonska

Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports

Epidermodysplasia verruciformis (EV) is a rare genetic disease characterized by an impaired immune response to human papillomavirus (HPV) and HPV-associated cutaneous oncogenesis. Chronic infection occurs with potentially oncogenic HPV types 5 and 8 as well as non-oncogenic types. Flat warts and pityriasis versicolor-like lesions begin to appear in early childhood and become widespread. In the fourth and fifth decades many patients begin to develop multiple cutaneous malignancies. It has been established that EV is mostly associated with mutations of genes EVER1 and EVER2, coding transmembrane proteins located in the endoplasmic reticulum and involved in zinc transportation.

A new and important problem is the occurrence of the EV phenotype in immunosuppressed individuals, especially in association with HIV, which has been called ‘acquired epidermodysplasia verruciformis.’ This differs in response to therapies and outcome. Two varieties of acquired EV are described: a generalized verrucosis associated with large common warts mainly of HPV-3 type (sometimes referred to as benign EV), and a variety associated with diverse HPVs of types not usually related to EV.

The high risk of malignant transformation in genetic EV seems to be reduced in the acquired variety.

Management strategy

No compound acts directly on HPV, and no therapy produces a complete and sustained clearing of both benign wart-like and keratotic lesions associated with oncogenic EV HPVs. A most important aspect of the management of EV is protection from ultraviolet radiation, which is a cancer cofactor. Light-avoiding behavior and topical sunblock creams (sun protection factor >50) are indicated. Other cancer cofactors (radiotherapy, immunosuppressants) must be avoided. Premalignant and troublesome benign lesions can be treated by a variety of destructive techniques: surgical (cryotherapy, shave excision, curettage, laser, full excision) or chemical (trichloroacetic acid, 5% 5-fluorouracil).

For more widespread lesions, with signs of premalignancy or malignancy, agents that modify keratinization are indicated, such as oral or topical retinoids, vitamin D₃ analogs, interferons, and imiquimod. Photodynamic therapy (PDT) can be useful for early malignancy. Larger malignancies can necessitate skin autografts.

Specific investigations

Family history and examination of other family members

HPV typing to identify potentially oncogenic and non-oncogenic HPV types

Evaluation of immune status and the presence of factors producing or enhancing immunosuppression: HIV, congenital immunodeficiency syndromes, iatrogenic immunosuppression

Human papillomavirus-associated tumors of the skin and mucosa.

Majewski S, Jablonska S. J Am Acad Dermatol 1997; 36: 659–88.

A CME article on HPV-associated tumors. The histology of verrucous lesions demonstrates a highly characteristic cytopathic effect, with clarification of cytoplasm and nucleoplasm, and prominent keratohyaline granules.

Common variable immunodeficiency syndrome associated with epidermodysplasia verruciformis.

Vu J, Wallace GR, Singh R, Diwan H, Prieto V, Rady P. Am J Clin Dermatol 2007; 8: 307–10.

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