What is Epidermodysplasia Verruciformis (EV), a rare skin disorder?

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From the Guidelines

Epidermodysplasia verruciformis (EV) should be treated with a combination of topical and systemic therapies, including topical retinoids, systemic retinoids, and destructive therapies, with a focus on regular dermatological monitoring and sun protection to prevent malignant transformation. The treatment of EV is challenging due to its rare and complex nature, involving abnormal susceptibility to human papillomavirus (HPV) infections, leading to widespread wart-like lesions and an increased risk of skin cancer 1.

Treatment Options

  • Topical retinoids like tretinoin 0.025-0.1% cream applied once daily may help manage lesions.
  • Systemic retinoids such as acitretin (25-50 mg daily) or isotretinoin (0.5-1 mg/kg/day) can be used for more extensive disease, though treatment duration is often long-term.
  • Destructive therapies including cryotherapy, electrodesiccation, or surgical excision are important for removing suspicious lesions.
  • Imiquimod 5% cream applied 2-3 times weekly may help for limited areas.
  • Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) and red light has shown histological clearance in one case report, but HPV was not eradicated, and new lesions appeared at 1 year 1.

Prevention and Monitoring

  • Patients must practice strict sun protection with broad-spectrum SPF 50+ sunscreen applied every 2 hours when outdoors, protective clothing, and sun avoidance between 10 AM and 4 PM.
  • Regular skin examinations every 3-6 months are essential for early detection of malignant transformation, particularly on sun-exposed areas. The genetic basis of EV, involving mutations in EVER1/TMC6 or EVER2/TMC8 genes, which impair cellular immunity against specific HPV types, explains why affected individuals cannot clear these viral infections effectively 1.

From the Research

Definition and Characteristics of Epidermodysplasia Verruciformis

  • Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by immunologic abnormalities, disseminated human papilloma virus infection, and early development of skin cancers 2.
  • It is an autosomal recessive disease with a heightened vulnerability to human papillomavirus (HPV) infection, which manifests as hyperpigmented or hypopigmented macular lesions, lesions resembling pityriasis versicolor (PV) and planar warts, and an increased risk of progressing to skin cancer, especially in sun-exposed areas 3.

Treatment Options for Epidermodysplasia Verruciformis

  • The therapeutic management of EV is not standardized, and several therapies have been tried, with variable outcomes 2.
  • Treatment options include:
    • Imiquimod 5% cream, which has been used to successfully treat EV lesions 4.
    • Ingenol mebutate (Picato), which has been used to treat Imiquimod-resistant EV 5.
    • A combination of acitretin and interferon alfa-2a, which has been found to be of value in the treatment of EV 6.
    • Oral retinoids and photoprotection, which have been prescribed to patients with EV to prevent the progression of skin cancer 3.
    • Photodynamic therapy and oral retinoids, which have been used in combination to treat acquired EV with excellent clinical outcome and long-lasting remission 2.

Prognosis and Complications

  • EV has an increased risk of progressing to skin cancer, especially in sun-exposed areas 3.
  • Patients with EV are at risk of developing squamous cell carcinoma (SCC) in sun-exposed areas, as well as other skin cancers 3.
  • Early diagnosis and treatment are essential to prevent the progression of skin cancer and improve the prognosis of patients with EV 2, 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acquired epidermodysplasia verruciformis: a comprehensive review and a proposal for treatment.

Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 2013

Research

[Successful symptomatic treatment of epidermodysplasia verruciformis with imiquimod 5% cream].

Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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