A Young Female With Multiple Skin-Coloured Lesions Over Hands and Feet.

INTRODUCTION

Acrokeratosis verruciformis of Hopf (AVH) is a rare genodermatosis characterised by the presence of multiple flat-topped, skin-coloured keratotic lesions, which are typically seen on the dorsum of hands and feet. The nails may be whitish and thickened and may have longitudinal ridges breaking at the distal edge. AVH typically develops during early childhood but can also occur as late as the fifth decade.^[1] AVH is a disorder of keratinisation with an autosomal dominant inheritance pattern and incomplete penetrance.

CASE REPORT

An eighteen-year-old female presented with multiple asymptomatic skin and light-coloured lesions over the hands [Figure 1] and feet [Figure 2] for three years.

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Figure 1:

Flat-topped skin-coloured papules on the dorsum of the hands.

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Figure 2:

Flat-topped skin-coloured papules on the dorsum of the feet.

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She denied similar complaints in other family members. On mucocutaneous examination, there were multiple skin-coloured flat-topped papules on the dorsum of both hands and feet following a linear pattern. A few skin-coloured discrete papules were also present on both forearms, predominantly on the extensor surface. Dermoscopic examination showed central white homogenous areas, central white network, and peripheral cobblestone appearance [Figure 3].

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Figure 3:

Dermoscopic image showing central white homogenous areas (black arrow) and peripheral cobble stone appearance (red arrow). (DermLite DL4 dermatoscope-3Gen, polarized, 10x).

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Mucosae and nails exhibited no abnormalities. The differential diagnoses of AVH, Keratosis Lichenoides Chronica (KLC), Darier’s disease (DD), and cutaneous warts were considered. Skin biopsy from a papule over the dorsum of the hand showed mild epidermal hyperplasia with marked lamellated and basket weave ortho-hyperkeratosis [Figure 4a]. The granular layer appeared slightly thickened and with mild papillomatosis, giving it a ‘church spire’ appearance [Figure 4b].

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Figure 4:

(a) Histopathology showing ortho hyperkeratosis, papillomatosis, hypergranulosis, and church spire appearance (H&E, 100x), (b) Histopathology showing characteristic “church spire” appearance (H&E, 400x). (H&E: Haematoxylin and eosin.)

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On the basis of clinical, dermoscopic, and pathological findings, she was diagnosed as a case of AVH. She was prescribed oral isotretinoin 0.5mg/kg/day, tretinoin 0.025% gel once daily, and urea 10% cream once daily. Significant improvement was seen in lesions after 3 months of medication, characterised by flattening of papules.

DISCUSSION

AVH, a disorder of keratinisation, is a rare genodermatosis that is present at birth or during early childhood, although onset may occur as late as the fifth decade of life. It occurs due to a single dominant genetic defect and occurs due to a mutation in the ATP2A2 gene that encodes for the sarcoendoplasmic reticulum calcium (SERCA) ATPase Phase 2 pump.^[2] Due to incomplete penetrance, there may not always be a family history despite an autosomal dominant pattern of inheritance. Clinically, it manifests as multiple localised symmetrical, dry, rough, skin coloured, flat-topped or warty papules on the dorsum of the hands and feet, knees, elbows, forearms or lower legs. Dyschromic macules are rarely reported in AVH, and few such lesions were present in our case. Thickened palmar skin and punctate keratoses on palms and soles may be present, but were not found in this case. There was no nail involvement.

Lesions identical to those of AVH can also be observed in patients with acral Darier’s disease or even in relatives of such patients. AVH is a limited form of DD due to clinical similarities and inheritance patterns. Features differentiating DD from AVH are the presence of dyskeratotic cells, predilection for sebaceous areas, and involvement of the oral mucosa. No such findings were observed in our case.^[3]

Histopathological findings in our case showed mild epidermal hyperplasia with marked lamellated and basket weave orthohyperkeratosis without acanthosis and parakeratosis. Sparse superficial perivascular lympho-histiocytic infiltrate was present, and there was no interface change or lichenoid pattern to the infiltrate. The granular layer was thickened along with papillomatosis, but no vacuolization, which gave it a ‘church spire’ appearance.

DD, epidermodysplasia verruciformis, plane warts, and seborrheic keratoses clinically mimic lesions of AVH, but they can be distinguished on the basis of histological features. AVH and DD can be distinguished histologically as acantholysis, parakeratosis, and dyskeratosis are found in DD but not in patients with AVH. Acral lesions in DD, although initially non-dyskeratotic, may eventually progress to dyskeratosis, whereas AVH consistently remains nondyskeratotic and non-acantholytic throughout life. This is because the keratinisation process in AVH is exaggerated but normal, whereas in DD, it is accentuated and altered.^[4]

KLC is a rare disorder characterised by the presence of erythematous to violaceous papules and plaques, which are arranged in a linear and reticulate pattern over the extremities. Oral, genital, and nail involvement is frequently found in adults.^[5] Histopathology of lesions in KLC shows lichenoid tissue reaction characterised by epidermal atrophy or acanthosis, parakeratosis, follicular plugging, and lichenoid lymphocytic infiltrate with basal cell vacuolization.^[6]

There is no definitive cure for AVH. Superficial ablation has been found to be effective in AVH. Other modalities of treatment that have been used are cryotherapy, laser therapy (CO₂ and Nd: YAG laser), keratolytic agents, and surgical excision. Oral isotretinoin and acitretin have demonstrated efficacy in alleviating symptoms throughout the therapy period.^[7-9] However, recurrence has been found after cessation of therapy.

CONCLUSION

AVH is a rare genodermatosis that frequently eludes timely diagnosis owing to its striking clinical resemblance to other acral keratotic disorders. This case exemplifies the role of clinico-dermoscopic and histopathological correlation, particularly in sporadic cases lacking a contributory family history, in differentiating AVH from mimics such as DD, KLC, and plane warts. Documentation of such cases is invaluable for medical education, as it sharpens diagnostic acumen, reinforces classic clinicopathological hallmarks, prevents misdiagnosis, unwarranted investigations, and inappropriate therapeutic interventions.