Medical Journal of Dr. D.Y. Patil Vidyapeeth

: 2017  |  Volume : 10  |  Issue : 2  |  Page : 195--197

Macular variant of acrokeratosis verruciformis of Hopf

Rita Vipul Vora, Nilofar Gulamsha Diwan, Nidhi B Jivani, Rochit Rajesh Singhal, Shailee Sanjay Gandhi 
 Department of Skin and VD, Shree Krishna Hospital, Karamsad, Gujarat, India

Correspondence Address:
Rita Vipul Vora
OPD No. 111, Shree Krishna Hospital, Anand, Karamsad - 388  325, Gujarat


Acrokeratosis verruciformis (AKV) of Hopf is an autosomal dominant condition characterized by multiple flesh-colored or lightly pigmented flat or convex warty papules over dorsa of hands, feet, knees, elbows, and forearms. It affects both sexes and is usually present at birth or appears in early childhood. Two forms of the disease have been described, namely, classical AKV and sporadic AKV. Histological examination differentiates it from other similar conditions. Superficial ablation is the treatment of choice. We represent a case of a young female with extensive lesions over contralateral limbs, of classical AKV interspersed with multiple hypopigmented macular lesions of AKV.

How to cite this article:
Vora RV, Diwan NG, Jivani NB, Singhal RR, Gandhi SS. Macular variant of acrokeratosis verruciformis of Hopf.Med J DY Patil Univ 2017;10:195-197

How to cite this URL:
Vora RV, Diwan NG, Jivani NB, Singhal RR, Gandhi SS. Macular variant of acrokeratosis verruciformis of Hopf. Med J DY Patil Univ [serial online] 2017 [cited 2019 Dec 9 ];10:195-197
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Acrokeratosis verruciformis (AKV) of Hopf was described by Hopf in 1931 and Niedleman and Mckusick reported the familial nature.[1] This condition is determined by an autosomal dominant gene characterized by multiple flesh-colored or lightly pigmented flat or convex warty papules over dorsa of hands, feet, knees, elbows, and forearms.[2] The forehead, scalp, flexures, and the oral mucosa are never affected.[3] It affects both sexes and is usually present at birth or appears in early childhood; however, it may be delayed till the fifth decade of life.[4] We represent a case of a young female with extensive lesions over contralateral limbs, of nonfamilial sporadic AKV interspersed with multiple hypopigmented macular lesions of AKV.

 Case Report

A 17-year-old female presented with complaints of multiple asymptomatic raised skin lesions over both extremities along with flat hypopigmented lesions over extremities and back since 2 years. She was relatively asymptomatic 2 years back when she developed 2–3 hypopigmented papules over dorsa of right hand [Figure 1]. After a period of about 1 month, similar lesions developed over both feet. She also developed multiple hypopigmented flat lesions over both forearms and legs. There was no complaint of itching, burning, or pain. Our patient denied any history or family history of similar lesions. Physical examination revealed numerous hypopigmented and skin-colored flat-topped papules, measuring 0.2–0.3 cm over dorsa of both hands, forearms, and both feet and legs up to knees (lesions were more over right upper limb and left lower limb) [Figure 2]. The forearms and back [Figure 3] had multiple discrete macular hypopigmented lesions. No punctuate keratosis in palmoplantar area and no nail involvement were seen. Oral cavity and genitals were normal. Routine investigations were within normal range. Keeping AKV and EDV as differentials, two biopsies were taken (the first one from papules over left shin and the second from hypopigmented macules over right forearm). Histopathological examination of both specimens showed hyperkeratosis, increase in thickness of granular layer, slight papillomatosis, and acanthosis. The rete ridges were slightly elongated and extended to a uniform level. Focal areas show elevations of the epidermis resembling church spires [Figure 4] and [Figure 5]. The subepithelial tissue shows inflammatory infiltrates comprised chronic inflammatory cells. Hence, the patient was diagnosed with AKV of Hopf.{Figure 1}{Figure 2}{Figure 3}{Figure 4}{Figure 5}

AKV of Hopf is an autosomal dominant genodermatosis of unknown etiology. Apart from the typical skin-colored, flat, warty papules on the dorsum of the hands and feet, examination may reveal thickening of palmar skin and punctate keratoses on the palms and the soles.[4] Interruptions of the dermal ridges in the finger pads and palms, identical to those seen in Grover, Galli–Galli, and Darier's diseases, are another rather common findings in AKV.[5] Nails may be whitish and thickened and have longitudinal ridges breaking at the distal edge.[3] The onset age of classical AKV is different from that of sporadic AKV. Classical AKV often occurs during childhood [6],[7] where Panja [3] reported the average onset age of AKV as 11 years. The onset age of sporadic AKV is much later than that of classical AKV. There is no difference between the clinical features and histopathological findings of familial AKV and nonfamilial cases. Clinically, both show asymptomatic flesh-colored to reddish brown flat papules resembling flat warts on the dorsa of the feet with histopathology showing unique finding of a “church spire.”[3],[8] Palmar and plantar keratoses have been reported in classical AKV,[3],[8] but not in sporadic AKV. Some authors have reported on ATP2A2 gene mutations in AKV.[6],[8] Dhitavat et al.[6] reported a novel P602L mutation within the ATP-binding domain of ATP2A2 in classical AKV. Furthermore, Berk et al.[9] reported an A698V codon change in ATP2A2 in sporadic AKV. The A698V codon change has never been described in patients with either classical AKV or Darier's disease.[8] These results suggest that the mechanism and gene mutation in sporadic AKV may differ from classical AKV. Although clinically similar, AKV is thought to remain nondyskeratotic and nonacantholytic throughout life, whereas acral lesions of Darier's disease show, upon careful histologic examination, various gradations of acantholytic dyskeratosis, especially in older lesions. Basically, the keratinization process in AKV is exaggerated but normal, whereas in Darier's disease, it is accentuated, altered, and faulty.[3] Darier's disease (keratosis follicularis) is the most important disorder to be distinguished from acrokeratosis. Darier's disease, AKV, epidermodysplasia verruciformis, plane warts, and seborrheic keratoses can be differentiated on the basis of histologic examination findings from biopsy samples from individual lesions. AKV Histopathology classically shows the hyperkeratosis without parakeratosis, hypergranulosis, acanthosis, and papillomatosis, resembling a church spire which helps in distinguishing the condition from other dermatoses like in EDV there is hyperkeratosis, acanthosis, and vacuolation in keratinocytes is more extensive affecting the upper half of the malpighian layer.[10] The only treatment considered effective for AKV is superficial ablation. Applications of retinoic acid have been helpful for some affected individuals, and cryotherapy or destructive lasers such as CO2 or neodymium-doped yttrium aluminum garnet have been tried. Lesions tend to persist throughout the life and become more prominent after prolonged sun exposure.[4] Transformation to squamous cell carcinoma has been reported in two cases,[3],[11] and there is one report that suggests a possible linkage of AKV and nevoid basal cell carcinoma syndrome.[12]

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1Niedleman ML, McKusick VA. Acrokeratosis verruciformis (Hopf). A follow-up study. Arch Dermatol 1962;86:779-82.
2Schueller WA. Acrokeratosis verruciformis of Hopf. Arch Dermatol 1972;106:81-3.
3Panja RK. Acrokeratosis verruciformis: (Hopf) – A clinical entity? Br J Dermatol 1977;96:643-52.
4Mohsin A. Acrokeratosis Verruciformis of Hopf. Available from: [Last accessed on 2004 Mar 02].
5Raff M, Szilvassy J. Specific dermatoglyphic patterns: A characteristic manifestation of acantholytic dyskeratotic dermatoses. J Am Acad Dermatol 1989;21 (5 Pt 1):958-60.
6Dhitavat J, Macfarlane S, Dode L, Leslie N, Sakuntabhai A, MacSween R, 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;120:229-32.
7Alain H. Acantholytic disorders of the skin: Darier-White disease, acrokeratosis verruciformis, Grover disease, and Hailey-Hailey disease. In: Wolff K, Goldsmith LA, Katz SI, Glichrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York: McGraw-Hill; 2006. p. 437.
8Herndon JH, Wilson JD. Acrokeratosis verruciformis (Hopf) and Darier's disease. Genetic evidence for a unitary origin. Arch Dermatol 1966;93:305-10.
9Berk DR, Taube JM, Bruckner AL, Lane AT. A sporadic patient with acrokeratosis verruciformis of Hopf and a novel ATP2A2 mutation. Br J Dermatol 2010;163:653-4.
10Patel N, Diwan N, Nair PA. Nonfamilial acrokeratosis verruciformis of Hopf. Indian Dermatol Online J 2015;6:110-2.
11Dogliotti M, Schmaman A. Acrokeratosis verruciformis: Malignant transformation. Dermatologica 1971;143:95-9.
12Humbert P, Laurent R, Faivre B, Agache P. Nevoid basal cell carcinoma syndrome and acrokeratosis verruciformis. Occurrence of two rare inherited autosomal dominant conditions in the same patient. Dermatologica 1990;180:169-70.