Dermatology Online Journal

Acrokeratosis verruciformis
Taylor DeFelice MD MPH, Maria Robinson MD, Rishi Patel MD, Hideko Kamino MD
Dermatology Online Journal 18 (12): 12

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York

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Abstract

We present a case of acrokeratosis verruciformis of Hopf in a 58-year-old woman with multiple, skin-colored, flat-topped, hyperkeratotic papules on the dorsal aspects of the hands and feet. Her lesions appeared at age 13 and her son developed similar lesions at about the same age. Acrokeratosis verruciformis of Hopf is a rare genodermatosis, which is distinct from keratosis follicularis; sporadic cases have also been described. Management options include cryotherapy, keratolytics, superficial ablation with CO2 or Nd:YAG lasers, topical retinoids, and acitretin.

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History

Figure 1	Figure 2

Figure 3

A 58-year-old woman presented to the Dermatology Clinic at Bellevue Hospital Center in April, 2010, for evaluation of skin-colored, hyperkeratotic papules on the dorsal aspects of the hands and feet. The lesions had been present for 45 years and were gradually increasing in number. They were sometimes pruritic. She denied other skin or nail lesions or systemic symptoms. Her 34-year-old son also had similar papules on the dorsal aspects of the hands beginning about puberty, but they were not so pronounced as the patient’s lesions. No other family members were affected. Past treatments included urea cream, salicylic acid 40 percent cream, clobetasol ointment 0.05 percent, tretinoin 0.1 percent cream, and a pumice stone. None of these treatments resulted in improvement.

Past medical history included hypertension, diabetes mellitus, hypercholesterolemia, and gastroesophageal reflux disease. Medications included simvastatin, omeprazole, metformin, atenolol, fosinopril, and amlodipine. She had no known allergies. A biopsy was obtained from a lesion on the dorsum of the hand.

Physical examination

Skin-colored, flat-topped, hyperkeratotic papules were present on the dorsal and lateral aspects of the hands and feet. There was no palmar, plantar, or nail involvement.

Laboratory data

None.

Histopathology

There is acanthosis and slight papillomatosis of the epidermis with hyperkeratosis. A Van Gieson stain shows normal elastic fibers.

Discussion

Acrokeratosis verruciformis of Hopf (AVH) is a rare, autosomal dominant genodermatosis that was first described by Hopf in 1931 [1]. It is characterized by multiple, skin-colored, flat-topped, hyperkeratotic papules on the dorsal aspects of the hands and feet, which occasionally extend to the forearms and lower legs. The lesions may resemble flat warts and are usually asymptomatic. There is no gender predilection. AVH arises at birth or in childhood, with an average age of onset at 11 years [2]. However, several cases have been reported of presentations in adulthood and seven sporadic cases have been described [3-9]. Punctate keratoses of the palms and soles may occur in genetic AVH although they have been described in only one sporadic case [3]. Nails may exhibit thickening with longitudinal ridges. None of the sporadic cases has displayed nail changes [2, 9].

The differential diagnosis includes verruca plana, the acral keratotic lesions of keratosis follicularis (Darier-White disease), epidermodysplasia verruciformis, stucco keratoses, and lichen planus. Examination of a skin biopsy specimen confirmed the diagnosis. Histopathologic features include hyperkeratosis, hypergranulosis, acanthosis, and papillomatosis that resembles church spires. Parakeratosis, dyskeratosis, acantholysis, and vacuolization are absent [10].

Patients with keratosis follicularis may develop AVH-like lesions acrally and it has been suggested that there is a link between the two entities, although this concept remains controversial. Clinically the lesions may be indistinguishable, but histopathologically they are distinct. Acral lesions of keratosis follicularis exhibit parakeratosis, dyskeratosis, and acantholysis [2, 4]. Few genetic analyses have been performed in patients with AVH. A study of one family affected with AVH in six generations identified a heterozygous P602L mutation in ATP2A2, which suggested that AVH is allelic to keratosis follicularis [11]. One analysis of a patient with sporadic AVH identified a novel ATP2A2 mutation, a A698V codon change, which has never been described in patients with keratosis follicularis [4]. However, an analysis of two families and one sporadic case with AVH failed to indentify ATP2A2 mutations [8]. Further genetic evaluation of AVH patients may help to elucidate the relationships between keratosis follicularis and genetic and sporadic AVH. Close follow-up of children with lesions consistent with AVH is indicated because the AVH-like lesions of keratosis follicularis may precede the classic lesions of keratosis follicularis elsewhere and initially lack dyskeratosis [4].

There is no standard treatment for AVH and lesions do not spontaneously resolve. Treatment modalities include cryotherapy, keratolytics, superficial ablation with CO2 or Nd:YAG lasers, and topical and systemic retinoids [5, 6, 12]. Acitretin has been used effectively in two patients, although in one case the lesions returned after treatment.

References

1. Hopf G. Über eine bisher nicht beschriebene disseminierte. Keratose (Akrokeratosis verruciformis) Dermatologische Zeitschrift 1931;60:227

2. Panja RK. Acrokeratosis verruciformis (Hopf)-a clinical entity? Br J Dermatol 1977;96:643 [PubMed]

3. Schueller WA. Acrokeratosis verruciformis of Hopf. Arch Dermatol 1972;106:81 [PubMed]

4. Berk DR, et al. A sporadic patient with acrokeratosis verruciformis of Hopf and a novel ATP2A2 mutation. Br J Dermatol 2010;163:653 [PubMed]

5. Farro P, et al. Unusual association between acrokeratosis verruciformis of Hopf and multiple keratoacanthomas: successful therapy with acitretin. J Dtsch Dermatol Ges 2004;2:440 [PubMed]

6. Serarslan G, et al. Acitretin treatment in acrokeratosis verruciformis of Hopf. J Derm Treat 2007;18:123 [PubMed]

7. Kaliyadan F, et al. Acrokeratosis verruciformis of Hopf associated with dilated cardiomyopathy. Indian J Dermatol 2009;54:296 [PubMed]

8. Wang PG, et al. Genetic heterogeneity in acrokeratosis verruciformis of Hopf. Clin Exp Dermatol 2006;31:558 [PubMed]

9. Bang CH, et al. Non-familial acrokeratosis verruciformis of Hopf. Ann Dermatol 2011;23:S61 [PubMed]

10. Rallis E, et al. Acrokeratosis verruciformis of Hopf (Hopf disease): case report and review of the literature. Dermatol Online J 2005;11:10 [PubMed]

11. Dhitavat J, et al. Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease. J Invest Dermatol 2003;120:229 [PubMed]

12. Bukhari I. Acrokeratosis verruciformis of Hopf: a localized variant. J Drugs Dermatol 2004;3:687 [PubMed]

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