Acrokeratosis Verruciformis of Hopf

Background: Acrokeratosis verruciformis is an autosomal dominant genodermatosis characterized by multiple warty lesions resembling plane warts typically observed on the dorsum of the hands and feet. Hopf first suggested the name acrokeratosis verruciformis in 1931. In 1947, Niedleman first published the largest series describing an Italian American family in which acrokeratosis verruciformis of Hopf occurred in 14 members. In the follow-up study in 1962, Niedleman and McKusick further described 24 cases in 4 generations of the same family. The number and distribution of cases in the latter report suggested an autosomal dominant mode of transmission.

Lesions identical to those of acrokeratosis verruciformis are also observed in many patients with acral Darier disease (also termed keratosis follicularis). To complicate matters further, lesions of acrokeratosis verruciformis have been reported in relatives of individuals with Darier disease. Considerable controversy surrounds the nature and relationship of acrokeratosis and Darier disease and whether they are manifestations of one genetic abnormality. Acrokeratosis verruciformis and acral Darier disease have been distinguished as 2 distinct entities in the literature. Although clinically similar, acrokeratosis verruciformis is thought to remain nondyskeratotic throughout life, whereas acral lesions of Darier disease show, upon careful histologic examination, various gradations of benign acantholytic dyskeratosis.

Darier disease (keratosis follicularis) is the most important disorder to be distinguished from acrokeratosis. Darier disease, acrokeratosis verruciformis, epidermodysplasia verruciformis, plane warts, and seborrheic keratoses can be differentiated by histologic examination of biopsy samples from individual lesions. The hard nevus of Unna can be differentiated clinically by its late onset.

Pathophysiology: The close similarity of Hopf disease to the acral warty lesion of keratosis follicularis has been noted by Hopf and Darier themselves. The similarities led later observers to postulate a relationship between the two diseases. The exact relationship between acrokeratosis verruciformis and Darier disease has not yet been satisfactorily resolved. A classic case of Darier disease poses no diagnostic problem. However, deciding whether a forme fruste of Darier disease (with atypical acral papules) is identical to acrokeratosis verruciformis remains difficult.

Frequency:

• Internationally: Unknown

Race: Acrokeratosis verruciformis has been described in individuals of many races.

Age: Acrokeratosis verruciformis is usually present at birth or in early childhood. Onset may be delayed until the fifth decade of life.

Treatment
Medical Care: The only effective treatment is superficial ablation. Treatment is not generally recommended, but medical and surgical treatments have been tried. Applications of retinoic acid have been helpful in some individuals. Destruction of the lesions with cryotherapy or laser, especially destructive lasers such as a carbon dioxide or Nd:YAG laser, may be used. Untreated lesions persist and become more noticeable after prolonged sun exposure because of darkening.

Medication
Drug Category: Retinoids -- Tretinoin has been reported to be successful in some individuals with these lesions.

Drug Name	Tretinoin (Avita, Retin-A) -- Developed to treat acne vulgaris. Alters maturation and differentiation of keratinocytes. Has been used for a variety of conditions, including flat warts, abnormalities of keratinization, and other keratoses. Available in 0.025%, 0.05%, and 0.1% concentrations in a variety of vehicles, including gels, solutions, and creams.
Adult Dose	Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric Dose	<12> >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose; pruritus, erythema, and a burning sensation may be noted, especially with higher strengths; hypopigmentation and, rarely, hyperpigmentation, may be noted locally