Zeba Hasan Hafeez  ( Department of Dermatology, Dow Medical College, Karachi. )
Hasina Thawerani  ( Department of Civil Hospital and Sind Laboratory, Karachi. )

Epidermodysplasia vcrruciformis is an inherited dis­ease, characterized by widespread and persistent infection with human papillorna virus. A case of generalized pityriasis versicolor like patches. plaques, papules and plane warts who later developed squamous cell carcinoma on the sternum is presented here.

A 30 years old barber from Larkana presented with generalized, non-itchy macules and papules, which had first appeared three years ago. A small papule developed on the sternum which gradually increased in size over a period oftwo years. It was painful and bled on trauma. In family history, he was born to normal, consanguinous parents. lie had five normal children. Consanguity has been present for many generations. On examination, hypopigmented macules and patches were seen on the trunk, atms, hands and legs. Scattered hyperpigmented papules and plaques were seen on the face, trunk, with fewer on the arms and legs (Figure 1).

Warty papules were present on the sides of the fingers, palms and soles. A 2”x I’ mobile growth, reddish and oozing with well defined, crusted margins was present on the sternum (Figure 2).

Lymph nodes were not enlarged. Nails and hair were normal. Laboratory investigations, including blood picture. ESR, blood sugar, urine, Lils and x-ray chest were normal. Biopsy of a papule from chest showed irregularly acauthotic epidermis with basket weave orthokeratosis over­lying papillornatous dermis. A few superficial keratinocytes showed perinuclear vacuolation. Several dysplastic epidermal cells were focally present at various levels within the epidermis. The dysplastic cells had hyperchromatic and pleomorphic nuclei surrounded by cytoplasm with bluish hue and occasional vacuoles. Mitoses were not evident. Patch\\\\ lymphocytic inflammatory infiltrate admixed with pigmented macrophages, was present within the upper dermis. Biopsy of growth on sternum showed a tumour com­posed of nests and islands ofkeratinizing, atypical squamous epithelial cells infiltrating inflamined and focally hemor­rhagic derinal collagen. Individual tumour cells showed mostly enlarged round nuclei with prominent nucleoli. Some nuclei appeared pleoinorphic and hyperchromatic. The tumour cells showed brisk mitotic activity.

Epidermodvsplasia verruciforrnis (EV) was first de­scribed by Lewandowsky and Lutz in 1922¹. This disease has no geographic restriction or racial preference, but occurs more commonly in regions where consanguity rate is high². This patient’s family history showed the latter characteristics. Epidermodysplasia verruciformis is an autosornal recessive disease^2,3, though an X- linked recessive inheritance⁴ has been reported. Clinically, there is widespread and persistent infection with I IPV giving rise to a characteristic combination of plane warts. pityriasis versicolor like lesions and reddish plaques. Typical common warts are often present, especially on the sides of the fingers, palms and soles. Malignant change is common but metastasis is rare, the tumour being locallyinvasive³ The average age of onset of benign and papular lesions is six years, although the onset may vary from the second to the third decade^1,2. This patient first developed the lesions at the age of 27. Tumours arising from EV lesions are either benign papillomas, seborrhoeic keratoses or premalignant actinic keratoses, squamous cell carcinomas or carcinomas in situ of the Bowenoid type. Squamous cell carcinoma ultimately develops in one or more lesions in about 20% cases, even before the age oftwenty, especially when the lesions havebeen present for under ten years³. In another study, malignant conversion of skin lesions occurred in more than half of the patients who were followed up for twenty to thirty years. It usually started after the age of thirty, mainly in the fourth or  carcinoma only a year after the appearance of EV skin lesions. The transformation from benign to malignant lesions appears to be proportional to the amount of sun exposure². Out-door occupations in sunny climates are closely related factors. Immunosuppressions due to any cause has a higher incidence of cutaneous carcinoma. Hunioral immunity is generally intact in EV patients. Cell mediated immunity appears to be markedly depressed, but preserved in patients with common warts⁵. In a study, regression of warts was associated with significant cell mediated immunity in four patients⁶. Deeply depressed cell mediated immunity is respon­sible for infection with potentially oncogenic viruses. Ten percent of EV patients are mentally retarded; while others have psychological disturbances¹. Atleast fifteen HPVtypes are characteristic of EV, including types 5, 8. 7, 12, 14, 15, 17, 19-25. 28 and 29. HPV5, 12, 17,20, 38 induce pityriasis versicolor like lesions⁷. HPV 14,20 and 21 have been isolated from plaques⁷ and HPV3 and 10 in plane warts of EV³. HPV 5,8 are known to prevail in skin carcinomas¹. HPV 12,14⁸,47 and 20⁹ have also been reported to cause cancer. Unfortunately, we had no facilities for the above investigations. Pathologically. there is hyperkeratosis and acanthosis. However, the vacuolation in the keratinocytes is more extensive and may affect the upper half to three quarters ofthe maiphigian layer. Viral particles can be identified ultrastructu­rally in the malphigian and basal cells. There is gradual progression to dysplasia¹⁰ as was observed in this case. There is no specific therapy for EV. Patients should be observed for the development of carcinomas and premalign ant lesions, which should be excised or locally ablated. Avoidance of sun exposure and use of sunscreens is indicated. Etretinate causes clinical improvement in some cases, but the viral infection persists histologically. Relapse occurs when the treatment is stopped¹¹. Failure of etretinate given for six months showed failure in one study¹². It is not known whether etretinate may p1-event dysplastic or malignant changes. Experimental therapies applied to EV patients included systemic and intralesional administration of interferons¹³ and retinoids¹⁴ and dialysable leukocyte extract (transfer fac­tor) ¹⁵. Partial or transitory effect was observed with the above. The promising new form of treatment is based on a combina­tion of 13-crisretinoic acid with interferon alpha or with cholecalciferol analogues¹⁶.

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