Epidermodysplasia verruciformis. (Case Report).

Abstract

Epidermodysplasia verruciformis is an uncommon cutaneous entity characterized by persistent human papillomavirus infection. A defect in cell-mediated immunity is the suggested causative factor. Numerous specific human papillomavirus types have been detected in this disease. Multiple nonmelanoma skin cancers are commonly seen in such patients; thus, early diagnosis is beneficial.

Key Words: epidermodysplasia verruciformis, human papillomavirus, skin cancer

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Epidermodysplasia verruciformis (EV) is a rare cutaneous disorder characterized by persistent human papillomavirus (HPV) infection. This disease results from a genetically determined defect in cutaneous immunity that leaves afflicted individuals susceptible to persistent HPV infection. In addition, there is an association with squamous cell carcinoma of the skin. Thus, early diagnosis and routine monitoring is essential for these patients. We present a 45-year-old male with epidermodysplasia verruciformis and review the literature.

Discussion

EV is a rare disorder of cutaneous immunity characterized by an inherited susceptibility to infection with specific HPV. It was first described by Lewandowsky and Lutz (1) in 1922. There does not appear to be any racial or geographic predilection, although there have been few reports of EV in individuals of African descent. (2) The initial cutaneous changes seen with EV often occur at a young age. (3) Lutzner (4) reported an association with mental retardation as exemplified in our patient.

EV typically presents with two main types of cutaneous lesions. Flat wartlike lesions that present as scaly hyper- or hypopigmented confluent patches and plaques are widely distributed on the hands, arms, and face. In addition, verrucous or seborrheic keratosis-like lesions are commonly seen. Skin cancers commonly occur in these patients, especially in sun-exposed areas. (3,5)

There is increasing evidence that dysfunction in cell-mediated immunity is a causative factor in EV; however, the specific immune defect has not been fully elucidated. (6) The underlying abnormality involves the inability to recognize EV-associated HPVs, which is marked by the inhibition of natural killer cells and cytotoxic lymphocytes. (3,6,7) Several studies have implicated a defect within keratinocytes. (6,7) The activity of Langerhans cell antigen presentation appears normal in EV, thus suggesting other cells cause inununotolerance to EV-associated HPVs. (7,8) The role of HPVs in tumorigenesis is supported by the detection of viral genome transcripts in EV-induced cancers. (9) The deletion of viral sequences and mutations within the viral genome have been speculative factors of such tumor progression. (10)

Numerous specific HPVs have been detected with EV; however, only a few (especially HPV-5 and HPV-8) have demonstrated an association with carcinoma. (3, 10) The presence of HPV-5 and HPV-8 as well as other EV-associated HPVs (HPV Types 9, 12, 14, 15, 17, 19-25, 36-38, 47, 50) are not pathogenic in-the normal population. (5,11) Steger et al (12) suggested that up to 20% of the population may subclinically harbor certain EV-associated HPVs. The association of HPV-5 and HPV-8 with carcinoma remains to be understood; however, these have been isolated in more than 90% of EVassociated squamous cell carcinomas. (5)

An autosomal recessive pattern of inheritance has been suggested, although sex-linked and autosomal dominant inheritance patterns have also been described. (4,5,13) Ultraviolet radiation appears to be a factor (along with HPV and relative immunosuppression) in the establishment of EV, as approximately 30 to 70% of patients with EV develop skin cancers with a predilection for sun-exposed sites. (14) Other populations that demonstrate an increased incidence of EV include renal transplant and immunosuppressed patients.

Since the majority of skin cancers arise in sun-exposed areas, strict avoidance of the sun combined with the use of sunscreens is warranted. Treatment of this disorder relies on careful surveillance and prompt treatment of premalignant and malignant lesions. Other treatments include systemic retinoids, 5-fluorouracil and 5-aminolaevulinic acid photodynamic therapy for early malignant or premalignant lesions. (3,5,14) Treatment with x-ray should be avoided as this often results in recurrence of skin cancers with aggressive rapid growth patterns. (3)

Conclusion

EV is a rare cutaneous disorder that manifests with persistent HPV infection. Genetic inheritance patterns have been implicated, resulting in defective cutaneous immunity against HPV. There is an association with squamous cell carcinoma of the skin, especially in sun-exposed sites. A multitude of specific HPV types have been associated with EV; however, only certain types (primarily HPV-5 and HPV-8) have been associated with carcinoma. Recognition of the cutaneous findings is paramount for the physician. Given their propensity for skin cancer, such patients must be counseled with regard to sun avoidance and strict use of sunscreens.

Accepted July 1, 2002.

References

(1.) Lewandowsky F, Lutz W. Em Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis). Arch Dermatol Syphilol 1922;141:193-203.

(2.) Jacyk WK, deVilliers EM. Epidermodysplasia verruciformis in Africans. Int J Dermatol 1993;32:806-810.

(3.) Jablonska S, Majewski S. Epidermodysplasia verruciformis: Immunological and clinical aspects Curr Top Microbial Immunol l994;186:157-175.

(4.) Lutzner MA. Epidermodysplasia verruciformis: An autosomal recessive disease characterized by viral warts and skin cancer. Bull Cancer 1978;65:169-182.

(5.) Harris AJ, Purdie K, Leigh IM, Proby C, Burge S. A novel human papillomavirus identified in epidermodysplasia verruciformis. Br J Dermatol 1997;136:587-591.

(6.) Majewski S, Skopinska-Rozewska E, Jablonska S, Wasik M, Misiewicz J, Orth G. Partial defects of cell-mediated immunity in patients with epidermodysplasia verruciformis. J Am Acad Dermatol 1986;15:966-973.

(7.) Cooper KD, Androphy EJ, Lowy DR, Katz SI. Antigen presentation and T-cell activation in epidermodysplasia verruciformis. J Invest Dermatol 1990;94:769-776.

(8.) Haftek M, Jablonska S, Szmanczyk J, Jarzabek-Chorzelska M. Langerhans cells in epidermodysplasia verruciformis. Dermatologica 1987;174:173-179.

(9.) Yutsudo M, Hakura A. Human papillomavirus type 17 transcripts expressed in skin carcinoma tissue of a patient with epidermodysplasia verruciformis. Int J Cancer 1987;39:586-589.

(10.) Deau MC, Favre M, Orth G. Genetic heterogeneity among human papillomaviruses (HPV) associated with epidermodysplasia verruciformis: Evidence for multiple allelic forms of HPV5 and HPV8 E6 genes. Virology 1991;184:492-503.

(11.) Astori G, Lavergne D, Benton C, Hockmayr B, Egawa K, Garbe C, et al. Human papillomaviruses are commonly found in normal skin of immunocompetent hosts. J invest Dermatol 1998;110:752-755.

(12.) Steger G, Olsewsky M, Stockfleth E, Pfister H. Prevalence of antibodies to human papilloma virus type in the human sera. J Virol 1990;64:4399- 4406.

(13.) Androphy EJ, Dvoretsky I, Lowy DR. X-Iinked inheritance of epidermodysplasia verruciformis: Genetic and virologic studies of a kindred. Arch Dermatol 1985;121:864-868.

(14.) Karrer S, Szeimies RM, Abels C, Wlotzke U, Stolz W, Landthaler M. Epidermodysplasia verruciformis treated using topical 5-aminoaevulinic acid photodynamic therapy. Br J Dermatol 1999;140:935-938.

RELATED ARTICLE: Key Points

* Epidermodysplasia verruciformis is an uncommon cutaneous entity characterized by persistent human papillomavirus (HPV) infection.

* A defect in cell-mediated immunity is the suggested causative factor.

* HPV-5 and HPV-8 are the primary HPV types involved; however, other associated types include HPV Types 9, 12, 14, 15, 17, 19--25, 36--38, 47, and 50.

* Multiple squamous cell skin cancers are common and thus early diagnosis is paramount.

Case Report

A 45-year-old white man presented with multiple small scaling lesions on his face and hands. The skin lesions began in childhood and persisted into adulthood. His medical history was significant for multiple (greater than 50) squamous cell carcinomas, a seizure disorder, and mental retardation. Surgical history included multiple excisions of cutaneous cancers. The patient had no known medication allergies and was taking thioridazine. He used tobacco but denied the use of alcohol. Physical examination revealed multiple verrucous, crusty, scaling plaques on the face and hands (Figs. 1 and 2) and disseminated hyperpigmented scaling macules on the trunk and arms (Fig. 3). The patient had numerous scars from previous cutaneous cancer excisions on his forehead and arms. A potassium-hydroxide examination from truncal lesions was negative for fungal elements. A punch biopsy obtained from the right forearm revealed an acanthotic epidermis with multifocal cytoplasmic vacuolization in the cells of the upper level kerat inocytes and prominent keratohyalin granules.

From the Section of Dermatology, Department of Medicine, The Medical College of Georgia, Augusta, GA; and Mercer University School of Medicine, Macon, GA.

Reprint requests to Joshua E. Lane, MD, Section of Dermatology, The Medical College of Georgia, 1004 Chafee Avenue, Augusta, GA 30912. Email: [e-mail]

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