Acrokeratosis verruciformis Q82.8

Hopf, 1931

Rare, autosomal-dominant inherited keratinization abnormality characterized by multiple, symmetrical, asymptomatic, skin-colored (rarely brownish), flat, wart-like papules on the dorsal aspect of the hands and feet (occasionally on other body parts such as knees, elbows, and forearms), typically associated with palmoplantar punctate keratosis and variable nail involvement (including leukonychia, thickening, grooves, longitudinal striae, and splitting). Questionable variant of dyskeratosis follicularis.

It is based on autosomal-dominant inherited mutations of the ATP2A2 gene, which is located on chromosome 12q23-24 (analogous to dyskeratosis follicularis).

Therefore, the clinical picture is considered by some authors as a variant of dyskeratosis follicularis. Apparently, mutations at different loci of the allele seem to cause the phenotypic expression of this clinical picture.

Remark: Mutations of the gene lead to defective enzyme formation and secondarily to inadequate replenishment of the calcium stores of the endoplasmic reticulum. This results in the expression of altered calcium-dependent adhesion molecules (desmosomal cadherins). These proteins are necessary for adhesion processes of epithelial cells.

Different start: Infancy to early adulthood.

Preferably back of hands and feet, more rarely forearms, knees, elbows.

Numerous lentil-sized, flat, skin-coloured to reddish-brown, mostly polygonal papules, some with warty surface. Confluence creates a cobblestone-like aspect. No pruritus.

Histology shows undulating hyperkeratosis with hypergranulosis and acanthosis, as well as a peaked papillomatosis. This produces a characteristic "steeple" appearance. Acantholysis or dyskeratosis are absent (in contrast to Darier's disease).

Verrucae planae juveniles

Verrucae vulgares

Epidermodysplasia verruciformis

Lichen planus

Dyskeratosis follicularis

Acrokeratoelastoidosis

Porokeratoses

Stucocoeratoses.

Keratolytically with vitamin A acid, tretinoin(e.g. R256, Cordes VAS) or salicylic acid 3-10% R227, if necessary under occlusion for a few hours . Alternatively: treatment with_CO2 or Erbium-YAG laser or cryosurgery in open spray procedure.

Transition into a spinocellular carcinoma possible.

Joint appearance with M. Darier is possible.

1. Dhitavat J et al (2003) Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease. J Invest Dermatol 120: 229-232
2. Dissemond J (2007) Generalized eczema and palmoplantar hyperkeratoses. Dermatologist 58: 460-464
3. Hafner O et al (1997) Acrokeratosis verruciformis-like changes in Darier disease. Dermatologist 48: 572-576
4. Hopf G (1931) On a previously undescribed disseminated keratosis (acrokeratosis verruciformis). Dermatol Zeitsch 60: 227-250
5. Hopf G (1932) On the keratoses occurring in Darier's disease on the hands and feet. Acta Derm Venereol 13: 720-734
6. Sun CW et al (2020) Guttate leukoderma and acrokeratosis verruciformis of Hopf: a rare combination in Darier disease. Dermatol Online J 26:13030/qt5938q4rj.