Acrokeratosis verruciformis of hopf along lines of blaschko.

Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis presenting as multiple plane wart-like lesions symmetrically distributed on dorsum of hands and feet. Its pathogenesis is unknown. A case of 24 years old female is described with multiple hyperpigmented, hyperkeratotic papules on the left side of body since 5 years along the lines of Blaschko. Histopathology showed changes of AKV. Other unusual findings were the absence of family history, extensive lesions with flexural, and genital involvement.

What was known?

Acrokeratosis Verruciformis is a genodermatosis presenting as multiple plain warts like lesion symmetrically distributed on the dorsum of hands and feet.

Introduction

Acrokeratosis verruciformis of Hopf (AKV) is a rare autosomal dominant cutaneous disorder first described by Hopf in 1931.[1] It is characterized by multiple flat-topped skin colored or fleshy, dull red to brown in color keratotic lesions resembling plane warts mainly observed on the dorsum of hands and feet. Lesions are usually present at birth but may appear later in infancy or at puberty. In some cases, onset may be delayed until the fifth decade of life. It has unknown etiology, affecting both sexes but is more common in males as compared to females with a ratio of 5:1.3.[2]

Lines of Blaschko have been recognized as a clinical marker for genetic mechanism of embryological development. Mosaicism refers to the presence of more than one type of cells that develop from a zygote. Four clinical patterns, caused by mosaicism, described by Happle are Blaschko's line (thin/type 1a, thick type 1b), checker – board pattern, phylloid pattern, and patchy pattern without midline separation.[3] The lines of Blaschko represent a pattern assumed by many different nevoid and acquired skin diseases on the human skin and mucosa.[4] They do not correspond to any known nervous, vascular or lymphatic structure, but represent the developmental growth pattern of the skin.[5] An embryological basis of these lines is not clear. Many congenital and acquired dermatosis are known to follow the lines of Blaschko-like epidermal nevus, Darier's disease, etc., To our knowledge till date, association of AKV along the lines of Blaschko is not reported.

Case Report

A 24-year-old female presented to skin OPD with lesions over the left side of body since 5 years. Initially, few lesions started over the left thigh, which gradually progressed to involve the left side of lower limb, feet, arm, forearm, and back in the span of 5 years. No history of any complaints in the form of itching, burning, or pain present. No history of similar complaints in any of the family members. No seasonal variation or any other systemic complaints present. On examination, multiple hyperkeratotic, hyperpigmented warty papules arranged unilaterally over the left side of body, i.e., back of thigh, lateral aspect of thigh, back of knee joint, and dorsum of ankle joint were present. On the back of thigh, lesions were seen in multiple bands [Figure 1]. Multiple such discrete papules were present over left upper back, shoulder [Figure 2a], axilla, medial, and lateral aspect of the left arm [Figure 2b] and forearm in the distribution lines of Blaschko [Figure 3]. Few warty papules were also present over the left side of labia majora. Nails and oral cavity were normal.

Figure 1

Multiple hyperkeratotic, hyperpigmented papules in multiple bands over back of the left thigh

Figure 2

Discrete papules over (a) left upperback and shoulder, showing an inverted “U”-shaped pattern and (b) upper arm in the linear pattern, along the lines of Blaschko

Figure 3

AKV over the left side of the body along the lines of Blaschko

Biopsy taken from back of the thigh showed hyperkeratosis, acanthosis, papillomatosis with circumscribed elevation of epidermis resembling church spires [Figure 4]. Rete ridges were slightly elevated extending to the uniform level. Dermis showed perivascular lymphocytic infiltrate and unremarkable adenexa structure. Changes were suggestive of AKV.

Figure 4

Histopathology shows hyperkeratosis, acanthosis, papillomatosis with circumscribed elevation of epidermis resembling church spires

Discussion

AKV is a disorder of keratinisation, a genodermatosis with unknown etiology. It is a rare heritable hyperkeratotic dermatosis characterized by multiple localized symmetrical flat skin colored wart-like lesions mainly on dorsum of hands and feet.[6] Isolated papules may develop on knees, elbows, forearm, and other parts of body. Forehead, scalp, flexures, and oral mucosa are never affected as reported by Panja.[1] Lesions may be finely granular to lichenified papules. Interruption of dermal ridges in finger pads and palms are seen with puntate pits. Nails show whitish discoloration, thickening, and may have longitudinal ridges breaking at distal ends. Histopathology, classically shows hyperkeratosis without parakeratosis, acanthosis, papillomatosis without vacuolization which resembles “church spire” and helps in ruling out other dermatosis.

Clinically, this case was confused with flat warts, seborrhoeic keratosis, epidermodysplasia verruciformis, and acral Darier's disease, which were ruled out by histopathology. Histopathology is indicated in chronic lesions to validate the diagnosis in AKV.[7]

The case presented with unilateral lesions particularly along the lines of Blaschko. These lines represent a form of human “mosaicism,” where two or more genetically distinct cell populations are present in an individual derived from a single zygote.[4] The pattern of lines of Blasckho seen in our patient can be classed as thin/type 1a on the left upper back and shoulder [Figure 2] and as thick type 1b on the back of thigh [Figure 1].[3] Lines of Blasckho are normally seen as inverted ‘U’ shape from the breast/back area onto the upper arm, and perpendicular lines down the front and back of the lower extremities.[4] The mechanism behind the appearance of dermatosis along the lines of Blaschko is unclear. Jackson suggested that their localization is partly determined by dermal tissue.[4] An inborn error of morphogenesis due to single mutant gene or stretching of skin during embryogenesis is also a proposed mechanism.[8] A case of unilateral Darier's disease was reported by Manimegalai et al.,[9] where histopathology shows features of AKV.

In this patient, lesions were extensive, with flexural and genital involvement, a rare occurrence, reported by Rege et al.[2] as well.

Appearance of disease in late adolescence and absent family history was also unusual findings. Nonfamilial cases like this case have been reported.[1011] The onset age of classical AKV is during childhood; however, the onset age of sporadic AKV is much later.[10] Similarly, palmar and plantar keratosis have frequently reported in classical AKV, but not in sporadic AKV.[10] In this patient, the onset was in late adolescence with no involvement of palms and nails.

It is still controversial whether AKV and keratosis follicularis (an acral variant of Darier's disease) are distinct entity or they are variable expression of the same disease. They are still considered to be distinct both genetically and histologically. The unique finding of AKV is a church spire while of Darier's disease is benign suprabasal dyskeratosis with corps rond,[1] which thus ruled out later condition in this case.

Lesions usually persist throughout life and become prominent after prolonged sun exposure. The effective treatment option is superficial ablation. Retinoic acid topically,[12] cryotherapy, CO2 and Nd:YAG lasers are other options.

Unusual findings such as unilateral lesions along the lines of Blaschko, extensive and flexural involvement, genital lesions, appearance of the disease in late adolescence, female gender, and absent family history are noteworthy and interesting which require to be notified.

What was known?

Acrokeratosis Verruciformis can present unilaterally along the lines of Blaschko