Epidermodysplasia verruciformis

Lewandowsky u. Lutz 1922.

Verrucosis generalisata, Lewandowsky-Lutz syndrome.

Very rare HPV-induced genodermatosis with polymorphous, pronounced wart infection and increased tendency to malignant degeneration. The triggering HPV types are 5, 8, 9, 12, 14, 15, 17, 19, 20, 21-25, 36, 38, 47, 50. HPV 5 and 8 can be detected in 90% of cases.

The skin lesions mostly develop during childhood and adolescence, but can also be visible at birth. No spontaneous healing.

• In 30% of all cases, a familial increased incidence has been described. Strikingly, the cellular immune defence is often impaired, which may be due to AR inheritance. A mutation of the EVER1 or EVER2 gene (Epidermodysplasia Verruciformis Endoplasmatic Reticulum genes) on chromosome 17q25, which code for membrane proteins of the endoplasmic reticulum, is being discussed. Mutations can lead to increased susceptibility to HPV infection.
• In total, a large number of rare HPV genotypes have been detected, some of which, however, also occur in healthy skin. An increased probability for the occurrence of non-melanoma skin cancer is shown in skin lesions with HPV 5 and 8.

Solid or confluent papillomas up to the size of a cent. They are divided into 2 manifestations. On the one hand, pityriasis versicolor-like flat, yellow-red or yellow-brown papules. These appear mainly on the face and trunk. On the other hand, efflororescences appear lichenoid, wart-like on the palms. Especially the latter have a higher risk of degeneration. Often, the skin lesions occur in combination with pigment spots.

• Clinical
• Dermatopathology
• PCR with HPV typing essential for diagnosis

All over the integument, but mainly on the face and hands. The palms of the hands and feet can also be affected. The mucous membranes, however, are left out.

Histological findings depend on the location and duration of the disease, but generally resemble verruca plana. However, dyskeratosis and pyknotic nuclei are frequently seen.

• Due to the high incidence of Bowen's disease, Bowen's carcinoma or squamous cell carcinoma (up to 60% of all patients, especially between 40-60 years of age), regular dermatological check-ups are indicated. Epithelial dysplasia can occur very early (often from the age of 30). Especially UV-exposed skin areas are affected.

• Although mostly in good general condition, immunosuppression should be ruled out.
• Consequent UV protection.
• Biopsy of skin lesions suspicious for malignancy.
• X-ray and UV radiation should be avoided.

Topical therapy

• Vitamin A acid derivatives are usually not effective.
• Immunomodulators
  • Imiquimod
    • Aldara® 3x weekly for 12 weeks.
      • off-label-use
      • Application: 3x/week for several weeks, maximum 16 weeks.
      • Necessary before ablation of the wart surface.
      • NW: Redness, itching, burning, erosion of the skin. Inform patient about this before starting therapy!
  • Salicylic acid/5-FU
    • Verrumal® Lsg. (combination of 0.5% fluorouracil lsg and 10% salicylic acid): 2-3x daily Verrumal should be used for about 6 weeks. CAVE: No concomitant use of brivudine.
    • Off-label
• PDT (off-label)

Systemic therapy (all drug therapies are off-label-use)

• Retinoids:
  • Acitretin
    • Neotigason® p.o.
      • Initial:0.5 mg/kg bw 1x tgl.
      • Maintenance dose: 0.1-0.2 mg/kg bw 1x tgl.
      • Blood samples: Before therapy and every 8 weeks: GOT, GPT, gamma-GT, triglycerides, cholesterol, creatinine, HDL; in women, reliable protection against conception and monthly pregnancy tests.
      • KI: severe renal or hepatic insufficiency, hyperlipidaemia;
      • WWW: with vitamin A (retinoids), tetracyclines and methotrexate; no blood donation (until 1 yr after therapy), pregnancy (until 2 yrs after therapy), lactation.
  • Interferon
    • Interferon alfa-2a
      • Pegasys® s.c.
        • Peginterferon alfa-2b
      • Cylatron® s.c.
    • Anithistamines
      • H1 blockers
        • 2. Generation
          • Loratadine
          • Claritine® 1x/day
          • Tbl. take on an empty stomach.
          • KI: Pregnancy, lactation, <12 y.
          • Note according to product information contraindicated in SS. Nevertheless, means of choice (see https://www.embryotox.de/loratadin.html).
      • Cryotherapy
      • Curettage

1. Carlson JA, Cribier B, Nuovo G, Rohwedder A. Epidermodysplasia verruciformis–associated and genital-mucosal high-risk human papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn. Journal of the American Academy of Dermatology 2008;59:279-94.
2. Favre M, Orth G, Majewski S, Pura A, Jablonska S, Baloul S. Psoriasis: A Possible Reservoir for Human Papillomavirus Type 5, the Virus Associated with Skin Carcinomas of Epidermodysplasia Verruciformis. Journal of Investigative Dermatology 1998;110:311-7.
3. Jacobelli S, Laude H, Carlotti A, et al. Epidermodysplasia Verruciformis in Human Immunodeficiency Virus–Infected Patients. Arch Dermatol 2011;147:590.
4. Lewandowsky F, Lutz W. Ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis). Arch f Dermat 1922;141:193-203.