Epidermodysplasia verruciformis in lipoid proteinosis: case report and discussion of pathophysiology.

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by mutations in extracellular matrix protein 1 (ECM1) that involves deposition of basement membrane-like material in the skin and other organs. Epidermodysplasia verruciformis (EV) is also a rare autosomal recessive genodermatosis involving susceptibility to human papillomavirus (HPV) infections and squamous cell carcinoma, caused in most cases by homozygous mutations in EVER1 or EVER2. We describe a case of EV in a patient with LP and discuss the pathophysiology. A 3-year-old Lebanese girl presented with hoarseness, beaded papules along the eyelid margins, waxy papules and plaques on her head and neck, and lichenoid verrucous papules on the forearms and hands. Histopathology of the waxy papules exhibited deposition of periodic acid Schiff-positive basement membrane-like material in the superficial dermis, characteristic of LP. The verruca plana-like lesions exhibited acanthosis and enlarged keratinocytes with pale blue-grey cytoplasm and a perinuclear halo, consistent with verrucae and EV. Polymerase chain reaction amplification and sequencing of ECM1, EVER1, and EVER2 demonstrated a homozygous point mutation, c.389C>T (p.Thr130Met), in exon 6 of ECM1 and a heterozygous point mutation, c.917 A>T (p.Asn306Ile), in exon 8 in EVER2, known to cause EV in homozygous patients. The homozygous point mutation c.389C>T in ECM1 may be a novel mutation causing LP. Verruca plana-like lesions seen in LP appear to represent a form of acquired EV. In this patient, a heterozygous mutation in EVER2 at c.917 A>T may also have conferred susceptibility to HPV infection.

[Biology of epidermodysplasia verruciformis-associated HPV]. / Biologie der Epidermodysplasia-verruciformis-assoziierten HPV.

The genus betapapillomavirus (betaPV) presently comprises more than 40 virus types including the so-called epidermodysplasia verruciformis (EV)-associated HPV, which were originally detected in EV-patients by Southern blot hybridization. BetaPV are ubiquitous in the general population and frequently establish themselves already during the first weeks of life. Hair follicles are regarded as natural reservoir. About 25% of betaPV detected in adults persist for at least 9 months. Due to very low virus production, seroconversion against betaPV starts sluggishly. Hyperproliferation of keratinocytes in psoriasis patients or after severe burns stimulates virus replication. Massive virus replication only occurs in EV-patients, associated with the induction of disseminated skin lesions with a high risk of malignant conversion. In 75% of EV-patients this can be put down to homozygous, inactivating mutations in the genes EVER1 or EVER2. A transgenic mouse model substantiated the crucial role of increased HPV8 oncogene expression, induced by UV-irradiation or wounding, for tumor induction.

A case of epidermodysplasia verruciformis with squamous cell carcinomas on non-sun-exposed areas of skin.

Epidermodysplasia verruciformis is an inherited disorder, characterized by multiple plane warts, pityriasis versicolor-like lesions, defects of cell-mediated immunity, and tendency to develop skin malignancies, primarily on sun-exposed areas. In this article, we present a case of epidermodysplasia verruciformis with multiple plane warts, pityriasis versicolor-like lesions, and squamous cell carcinomas on non-sun-exposed areas of skin. After acitretin prescription, significant improvement was found in plane warts, but not in pityriasis versicolor-like lesions.