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CASE REPORT
Epidermodysplasia verruciformis in two siblings responding to retinoids Yasmeen Jabeen Bhat, Shazmeen Ashraf, Iffat Hassan Department of Dermatology, Sexually Transmitted Diseases and Leprosy, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India ABSTRACT Epidermodysplasia verruciformis (EV) is a rare genetic disease caused by human papilloma virus, presenting with pityriasis versicolor‑like, verruca‑like, and seborrheic keratosis‑like plaques and may predispose to cutaneous malignancy. We report two siblings with EV whose lesions regressed with systemic retinoids. Key words: Epidermodysplasia verruciformis, human papilloma virus, retinoids
INTRODUCTION
E
pidermodysplasia verruciformis (EV), first described in 1922 by Lewandowski and Lutz, is a rare genetic disease. It is characterized by a particular susceptibility to cutaneous infections with human papilloma virus (HPV) types in the genus β which do not produce clinical lesions in immunocompetent individuals. The HPV detected in EV are 3, 5, 8 (most frequently detected) 9, 12, 14, 15, 17, 19–25, 36–38, 47, 49, 50, etc. The disease usually manifests in childhood with highly polymorphic, widespread lesions.[1] Clinically, it presents with a characteristic combination of pityriasis versicolor‑like lesions, reddish verruca‑like and seborrheic keratosis‑like plaques with a potential for malignant transformation.[2]
CASE REPORT A 12‑year‑old male boy, a product of consanguineous marriage, presented with multiple, light brown, and flat white lesions on face and forehead since last 5–6 years; initially it started with flat white lesions on the face which was followed by light brown lesions on forehead within a period of 2 months. There was Access this article online Quick Response Code
Website: www.ijpd.in DOI: 10.4103/2319-7250.184328
also a history of photosensitivity. There was history of similar complaints in the other sibling who was an 18‑year‑old male. In the elder sibling, these lesions first started in the retroauricular area at the age of 5–6 years and then gradually spread to involve neck, upper limbs, trunk, and lower limbs over a period of 2 months and he also gave a history of recurrent chest infections and photosensitivity. On examination, there were multiple hyperpigmented and hypopigmented macules resembling pityriasis versicolor, present predominantly on the forehead, face, neck, and chest. Moreover, there were multiple warty papules present on chin and dorsum of both hands [Figures 1a and 2a]. All the baseline investigations including complete blood count, liver function tests, and lipid profile were normal. Potassium hydroxide of skin scrapings was negative. Skin biopsy was done in ADDRESS FOR CORRESPONDENCE Dr. Yasmeen Jabeen Bhat, Department of Dermatology, Sexually Transmitted Diseases and Leprosy, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India. E‑mail:
[email protected] This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact:
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How to cite this article: Bhat YJ, Ashraf S, Hassan I. Epidermodysplasia verruciformis in two siblings responding to retinoids. Indian J Paediatr Dermatol; doi: 10.4103/2319-7250.184328.
© 2016 Indian Journal of Paediatric Dermatology | Published by Wolters Kluwer ‑ Medknow
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[Downloaded free from http://www.ijpd.in on Saturday, July 16, 2016, IP: 117.216.140.135] Bhat, et al.: Epidermodysplasia verruciformis responding to retinoids
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Figure 2: (a and b) Lesions on hands before and after treatment a
b
Figure 1: (a and b) Lesions on face before and 8 weeks after isotretinoin therapy
the elder sibling which showed the features consistent with EV. The patient was put on isotretinoin after the investigations, along with sun protective measures. The elder sibling was put on 20 mg and the younger one on 10 mg of isotretinoin. On follow‑up at 8 weeks, patients showed good response [Figures 1b and 2b].
DISCUSSION EV is a rare genetic dermatosis which is caused by HPV. It usually begins in childhood and continues throughout the patient’s lifetime. It presents clinically with a characteristic combination of pityriasis versicolor‑like lesions, reddish verruca‑like and seborrheic keratosis‑like plaques. The lesions are preferentially located on sun‑exposed sites. These patients show a defect of cell‑mediated immunity that is specific toward the causative HPVs.[3] This inability to recognize and reject HPVs leads to lifelong lesions/ disease. Interestingly, these EV associated HPVs have been also involved in both benign and malignant proliferation of keratinocytes, as in the early stages of carcinogenesis.[4] The convincing oncogenic potential of HPV 5 and 8 in cutaneous malignancies of EV patients has evoked a considerable interest among clinicians and basic researchers for this rare genetic disorder as a model of cutaneous carcinogenesis.[2,5] It is often associated with IgM deficiency and HIV infection.[3] However, the underlying defect in EV is still not well understood. This susceptibility of human keratinocytes to the HPV in EV is usually inherited through an autosomal recessive gene, and pathogenic mutations have been detected in EVER1/TMC6 and EVER2/TMC8 genes mapped to a locus on chromosome 17q 25 that encodes integral membrane proteins of unknown significance in the endoplasmic reticulum.[6] A high frequency of parental consanguinity is usual in most reported cases, and more than 30% of the siblings acquire the disease at some or the other stage.[5] Nevertheless, cases with autosomal dominant or X‑linked inheritance too have been reported.[7] Mutated 2
EVER1 and EVER2 genes in epidermodysplasia patients may control the infection of other viruses.[8] The role of etretinate and acitretin has been seen in numerous studies.[9,10] However, these are only palliative treatments. Patients need a stringent sun protection and need to be observed lifelong to detect any premalignant or malignant change. Systemic retinoids have been used to maintain the remission in EV.[11] In our case, the lesions also showed a good response to isotretinoin along with sun protection. Declaration of Patient Consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/ her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial Support and Sponsorship Nil. Conflicts of Interest There are no conflicts of interest.
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