Remission of epidermodysplasia verruciformis-like skin eruption after highly active antiretroviral therapy in a human immunodeficiency virus-positive patient

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Sir, Epidermodysplasia verruciformis (EV) is a rare, usually familial, disease characterized by the development of multiple papules resembling flat warts and macular skin lesions that with time give rise to squamous cell carcinomas in up to 60% of patients in ultraviolet (UV)‐exposed skin. EV skin tumours are induced by a group of closely related human papillomaviruses (HPVs) that occur in many non‐melanoma skin cancers and in their precursor lesions.1,2 Immunosuppressed patients seem to be particularly prone to infections with EV‐associated HPV types.3 A few cases of an EV‐like eruption have been described in association with human immunodeficiency virus (HIV) infection.4,5 However, no data are currently available with regard to the clinical course of these lesions over an extended observation period. We present clinical, histological and virological data, in addition to 7‐year follow‐up details, of an HIV‐positive patient with an EV‐like eruption. A 45‐year‐old man presented in 1994 at stage C3 with an asymptomatic, cosmetically disturbing, skin eruption progressing slowly on the chest and the dorsal upper extremities over the past 3 months. He had been known to be HIV‐positive since 1983, and was being treated with zidovudine. He admitted to regular UV exposure for cosmetic reasons. Examination showed about 50 disseminated lesions on the sun‐tanned skin of the chest, back and face. They were either flat, warty, slightly keratotic papules or whitish, sharply bordered macules. Lesions measured 2–6 mm in diameter and were round or irregular in shape, and some had a lid‐like scale. The eruption was reminiscent of pityriasis versicolor, although some lesions had the appearance of flat warts. A biopsy from a warty lesion on the back showed features reported to be characteristic of infection with EV‐specific HPV types in immunosuppressed patients. Overall, cellular atypia was not prominent. During the observation period, our patient's EV‐like lesions slowly increased in number and spread over the neck and face. Two years later, highly active antiretroviral therapy was started with stavudine, lamivudine and indinavir, which induced a remarkable decrease of viral load in blood from 2·5 × 105 to 2·0 × 103 viral copies mL−1. When our patient developed severe Mycobacterium avium‐intracellulare complex (MAC) infection with mediastinal lymphomas, he was treated with amikacin, clarithromycin, isoniazid, myambutol, protionamide, pyrazinamide and rifampicin. Skin lesions cleared rapidly thereafter and disappeared entirely, except for three to five minute, asymptomatic lesions of the chin. Concurrently, there was an increase in number of CD4+ helper T cells in our patient's serum, from 10 to 50 mm−3. When antiretoviral therapy was continued with nelfinavir, stavudine and lamivudine, the remission of EV‐like lesions persisted, along with continuous expansion of T‐cell numbers up to 300 mm−3 and a permanently low viral load of 200 copies mL−1. No skin cancer or new lesions except for palmar and periungual warts were observed during the subsequent 3‐year follow‐up. HPV analysis was performed following DNA isolation from paraffin‐embedded biopsy material.6 Five primer sets were used, one consisting of group‐specific MY09/11 primers, which detect the classical ‘genital types’ of HPVs,7 and four primer sets (A–D), which detect a broad spectrum of different HPV types.8 Viral DNA was observed with the primers A, B and D. Southern blot hybridization with a panel of different HPV reference types was performed under stringent conditions (Tm− 20 °C).9 A strong signal was observed with the EcoRI fragment of HPV5, which encompasses part of the early genomic region. Weaker reactions occurred with the sequences of HPVs 8, 14, 19 and 21, all of which belong to the same phylogenetic sub‐branch of the EV‐associated virus types.10 An interesting feature of our patient was that, in contrast to EV where the skin lesions persist over many years, he went into almost complete remission and has not developed new lesions over the past 3 years. This is all the more surprising in view of the continuing occurrence of the warts, known to be induced by the non‐EV‐HPVs. The mechanisms involved in this selective defence against different types of HPV are poorly understood. Reasons for the rapidly disappearing EV‐like lesions in our patient could be either immune reconstitution with increase of CD4+ helper T cells, or an effect of MAC therapy. Long‐term remission of the EV‐like skin eruption must be considered to be due to combined antiretroviral therapy, along with permanently high T‐cell numbers and a low viral load. The induction of EV and EV‐like lesions has been proposed to be UV‐related because of the predominant distribution of the rash in sun‐exposed areas.4 With the increased survival of patients with HIV infection due to treatment advances, UV exposure is discussed as being contraindicated in HIV patients, although no adverse effects of short‐term UVB treatment were observed in a recent study.11 The lack of recurrence of the virus‐infected EV‐like skin lesions and of development of skin cancer despite continued exposure to UV radiation in our patient is in line with the latter findings.