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Epidermodysplasia verruciformis

Author: Vanessa Ngan, Staff Writer, 2006. Updated by Dr Jannet Gomez, December 2016.


Epidermodysplasia verruciformis — codes and concepts
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What is epidermodysplasia verruciformis?

Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive inherited skin disorder characterised by a chronic eruption of brownish plaques

A similar disorder, known as acquired epidermodysplasia verruciformis, may arise in patients with impaired immunity

What causes epidermodysplasia verruciformis?

Each epidermodysplasia verruciformis patch is caused by an infection with a subtype of human papillomavirus (HPV).

HPV has numerous subtypes, which cause a wide range of viral warts. Some subtypes of HPV have minimal or no clinical effect in most people yet the same subtypes result in the clinical features of epidermodysplasia verruciformis in people with an impaired immune response to the virus. More than 30 subtypes of HPV have been implicated.

Who gets epidermodysplasia verruciformis?

Epidermodysplasia verruciformis is usually an autosomal recessive inherited disorder, which means that the individual has gained an abnormal EV gene from each parent. The parents of about 10% of patients with epidermodysplasia verruciformis are blood relatives (ie, the parents share a common ancestor). In a few cases, sex-linked and autosomal dominant inheritance patterns have also been reported.

Epidermodysplasia verruciformis is often due to mutations in the EVER1 or EVER2 genes on chromosome 17q25. The mutation decreases cell capacity to fight HPV infections. In cases that lack this mutation, mutations in RAS homolog gene family member H (RHOH), MST1 deficiency, and splicing deficiency in the gene encoding LCK (lymphocyte specific kinase) have been found.

The lesions usually start to appear during childhood and persist. About 7.5% of cases appear in infancy, 61.5% in children aged 5–11 years and 22.5% in puberty. The disease affects both males and females and people of all races.

Acquired epidermodysplasia verruciformis is a result of HIV infection, organ transplantation or a lymphoma.

What are the clinical features of epidermodysplasia verruciformis?

Two clinical presentations have been described in epidermodysplasia verruciformis.

  • White, pink, reddish brown, dark brown or violet flat-topped papules and plaques with a scaly surface and irregular borders.
  • Verrucous or seborrhoeic keratoses-like lesions. These are raised brown warty lesions. 

Warts occur in irregular clusters of a few to over a hundred lesions. They are especially prevalent in sun-exposed areas such as the hands, feet, face, and earlobes. Plaque-like lesions usually appear on the trunk, neck, arms and legs. The palms, soles, armpits and external genitals may also be involved. 

What are the complications of epidermodysplasia verruciformis?

A major concern for patients with epidermodysplasia verruciformis is that in 30-60% of EV patients the lesions may transform into skin cancers; these are mostly cutaneous squamous cell carcinoma and intraepidermal squamous cell carcinoma. Basal cell carcinoma and adnexal tumours are less common. Malignant tumours are usually found in patients 30–50 years of age.

Over 90% of EV-associated skin cancers contain HPV types 5, 8, 10, and 47. EV lesions caused by HPV 14, 20, 21, and 25 usually remain benignExposure to sunlight or ultraviolet radiation increases the chance that a benign wart will develop into skin cancer

How is epidermodysplasia verruciformis diagnosed?

Diagnosis is usually clinical. Epidermodysplasia verruciformis is suspected when there are a large number of treatment-resistant viral warts. A skin biopsy may reveal characteristic features (see epidermodysplasia verruciformis pathology).

Some laboratories can report the subtype of HPV by polymerase chain reaction (PCR).

What is the treatment for epidermodysplasia verruciformis?

Epidermodysplasia verruciformis is a lifelong disease. Even though lesions can be treated or removed as they appear, the lesions develop throughout life.

Currently there is no treatment to prevent new lesions from occurring. The management of EV involves a combination of medical and surgical treatments alongside patient counselling, education and regular surveillance (especially if immunocompromised).

  • Stress the importance of following sun protection strategies especially if living at high altitude and/or working outdoors. Exposure to sunlight (UVB and UVA) has been shown to increase the rate of EV lesions turning into skin cancers.  
  • Encourage smoking cessation.
  • Treat and remove the lesions in the same way as other viral warts, using a chemical treatment, cryotherapy, electrosurgery or laser ablation.
  • Oral and topical retinoids (isotretinoin and acitretin), fluorouracil and imiquimod may be helpful.
  • Experimental therapies for epidermodysplasia verruciformis and skin tumours include intralesional interferon, a combination of isotretinoin and interferon alpha or cholecalciferol (vitamin D) analogues.
  • Surgical excision and reconstruction are used for invasive skin cancers.

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References

  • OMIM – Online Mendelian Inheritance in Man (search term Epidermodysplasia verruciformis)
  • Book: Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth edition. Blackwell Scientific Publications.
  • Kalińska-Bienias A, Kowalewski C, Majewski S. The EVER genes – the genetic etiology of carcinogenesis in epidermodysplasia verruciformis and a possible role in non-epidermodysplasia verruciformis patients. Advances in Dermatology and Allergology/Postȩpy Dermatologii i Alergologii. 2016;33(2):75-80. doi:10.5114/ada.2016.59145. PubMed.
  • de Oliveira, W.R., Festa Neto, C., Rady, P.L., and Tyring, S.K. Clinical aspects of epidermodysplasia verruciformis. J Eur Acad Dermatol Venereol. 2003; 17: 394–398. PubMed.
  • Crequer A, Troeger A, Patin E, Ma CS, Picard C, Pedergnana V, et al. Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections. J Clin Invest. 2012 Sep. 122 (9):3239-47. PubMed.
  • Crequer A, Picard C, Patin E, D'Amico A, Abhyankar A, Munzer M, et al. Inherited MST1 deficiency underlies susceptibility to EV-HPV infections. PLoS One. 2012. 7 (8):e44010. PubMed.
  • Li SL, Duo LN, Wang HJ, Dai W, Zhou EH, Xu YN, et al. Identification of the LCK mutation in an atypical epidermodysplasia verruciformis family with T cell defects and virus-induced squamous cell carcinoma. Br J Dermatol. 2016 Apr 18. PubMed.
  • Agrawal, Prachi G., et al. Epidermodysplasia verruciformis: An unusual malignant transformation. Indian Journal of Dermatology, Venereology, and Leprology 79.1 (2013): 97. PubMed.
  • Hoffner MV, Camacho FM. Surgical treatment of epidermodysplasia verruciformis. Dermatol Surg. 2010 Mar. 36(3):363-7. PubMed.

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