Darier's disease

Abstract

Acrokeratosis Verruciformis of Hopf (AKV) is a rare autosomal dominant genodermatosis. It usually develops during early childhood affecting both sexes equally. Typically, the lesions are warty to convex, brownish to skin-colored papules on the dorsa of the hands and feet, forearms and legs. A possible relationship with Darier disease has long been postulated on a clinical basis mainly. But recently, evidence has suggested that AKV and Darier disease are allelic disorders. I am reporting these two unrelated cases as a unilateral localized variant of AKV.

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Case 1

A 20-year-old Saudi female presented with a 10-year history of scattered pinkish papules of 2-6 mm in diameter on the dorsal aspect of her right hand and right forearm. The patient noticed that these lesions were increasing in number slowly and gradually on the same site. She never sought medical advice because they were symptomless. Her past medical history was insignificant and family history was negative for similar condition. On examination of her skin, 2-6 mm pinkish papules were seen on the dorsa of her right hand and right forearm only (Figure 1). The rest of her skin was free of any similar lesions. Our differential diagnosis included persistent chronic verruca vulgaris and acrokeratosis verruciformis of hopf (AKV). Biopsy of one lesion showed hyperkeratosis, acanthosis, church spires appearance and papillomatosis with some degree of hypergransulosis but no vacuolization or parakertosis (Figure 2). Our final diagnosis was acrokeratosis verruciformis of Hopf and she was treated with liquid nitrogen.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Case 2

A 21-year-old Saudi male presented with a 12-year history of multiple pink colored papular lesions on the dorsa of his left hand and left side of his forehead. In the previous 2 years, they were increasing in number and size. The patient was treated as a case of warts and cryotherapy was done intermittently several times but with not much improvement. His past medical history was not significant and none of his siblings had similar lesions. On examination of his skin, 2-3 mm verrucous and convex pinkish papules were seen on the dorsal aspect of his left hand and on the left side of the forehead while the rest of his skin and nails were completely free of any lesion. Our differential diagnosis included persistent chronic verruca vulgaris versus acrokeratosis verruciformis of hopf. Biopsy was taken from a lesion on the dorsal aspect of the left hand and it showed similar changes as in the first case. The patient was finally diagnosed as a case of acrokeratosis verruciformis of Hopf and he was treated with liquid nitrogen for multiple sessions. He was satisfied with the outcome.

Discussion

AKV is a rare autosomal dominant genodermatosis but sporadic cases have been reported. It usually develops during early childhood affecting both sexes equally (1). It was first described by Hopf as a localized disorder of keratinization (2). Typically, the lesions are warty to convex, pinkish to skin-colored papules. The sites of predilection include dorsa of the hands and feet with the extensor aspects of the forearms and the legs. In addition, punctuate pits covered with pinhead size horny material could be seen in the palms and the soles. Nails show longitudinal striations, splitting, luekonychia and subungual hyperkeratosis (3). A possible relationship with Darier's disease has long been postulated on a clinical basis mainly. Recently, the defective gene in Darier's disease has been identified as ATP2A2 which encodes for the sarco(endo)plasmic reticulum Ca2+ ATPase2 pump. More recently, a P602L mutation in ATP2A2 was identified in AKV thus providing evidence that AKV and Darier's disease are allelic disorders (4). Interestingly, the lesions of AKV never occurs on the face, scalp and other sebaceous sites and there is no dyskeratosis as compared to Darier's disease. My patients had chronic persistent localized unilateral lesions which could imply that AKV could have a localized variant, possibly related to blaschko lines in its distribution. The Classic histologic findings of AKV include hyperkeratosis, acanthosis, and papillomatosis with some degree of hypergransulosis without vacuolization or parakertosis (5). "Church spires," which can be seen in AKV, consist of discrete pointed epidermal upgrowths resembling church spires (6). Rarely, malignant transformation to squamous cell carcinoma could occur (7). Treatment modalities are not completely curative which include: superficial destruction by liquid nitrogen, shave excision or carbon dioxide laser ablation (8).

References

1. Niedleamn ML, McKusick VA. Acrokeratosis Verruciformis (Hopf). Arch Dermatol 1962; 86:779-82.

2. Hopf G. Uber eine nicht beschriene disseminierte keratose (Acrkeratosis Verruciformis). Dermatol Z 1931; 60:227-50.

3. Blanchet-Bardon C, V et al. Acrokeratose Verruciforme de Hopf ou maladie de Darier acral. Ann. Dermatol Venereol 1988; 115:1229-32.

4. Dhitavat J, et al. Acrokeratosis Verruciformis of Hopf is caused by Mutation in ATP2A2: Evidence that is allelic to Darier's Disease. J Invest Dermatol 2003; 120(2): 229-32.

5. Schueller WA, Acrokeratosis verruciformis of Hopf. Arch Dermatol 1972; 106:81-3.

6. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 6th ed. Philadelphia, Pa: JB Lippincott. 1983:83-4.

7. Dogliotti M, Schmaman A. Acrokeratosis Verruciformis: Malignent Transformation. Dermatologica 1971; 143:95-9.

8. Chapman-Rolle L, et al. Persistent Flat-Topped papules on the extremities. Arch Dermatol 1994; 130:508-12.

IQBAL BUKHARI MD

ASSISTANT PROFESSOR, DEPARTMENT OF DERMATOLOGY, KING FAISAL UNIVERSITY, COLLEGE OF MEDICINE AND MEDICAL SCIENCES, ALKOBAR, SAUDI ARABIA

ADDRESS FOR CORRESPONDENCE:

Dr. Iqbal A. Bukhari

King Fahad Hospital of the University

P.O. Box 40189

Alkhobar 31952, Saudi Arabia

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E-mail: consultant@dermatologyclinics.net

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