Bilateral Systematized Epidermolytic Verrucous Epidermal Nevus: A Rare Entity.

Verrucous epidermal nevi are congenital, noninflammatory cutaneous hamartomas composed of keratinocytes. They follow the lines of Blaschko and show hyperkeratosis without cellular atypia. The routine histology shows variable amount of hyperkeratosis, acanthosis and papillomatosis and rarely epidermolytic hyperkeratosis. We saw a 3-year-old boy with bilaterally symmetrical, systematized verrucous plaques along the lines of Blaschko extensively involving the trunk and extremities but sparing the face and palmoplantar skin. Histopathology showed features of epidermal nevi with prominent epidermolytic hyperkeratosis. We report here the case for the rarity of this entity.

What was known?

Epidermal nevi may show epidermolytic hyperkeratosis on histology.

Introduction

Epidermal nevi are hamartomatous proliferations of the epithelium, including keratinocytes, sebocytes, pilosebaceous units, eccrine glands, or apocrine glands. Verrucous epidermal nevi (VEN) are non-inflammatory keratinocytic hamartomas composed of keratinocytes.[1] VENs are characterized by linearly arranged, closely set, gray-brown to black verrucous papules. The term systematized denotes many linear lesions limited to one side of the body or having a bilateral symmetrical distribution. The histological changes of VEN are variable hyperkeratosis, acanthosis and papillomatosis. Apart from this usual picture there are some rarer histological patterns including epidermolytic hyperkeratosis.[2] Epidermal nevi of the epidermolytic type are rare and represent mosaic expression of epidermolytic hyperkeratosis also known as linear or nevoid bullous ichthyosiform erythroderma (BIE). We hereby report a case of extensive bilaterally symmetrical systematized epidermal nevus occurring along the lines of Blaschko and showing epidermolytic hyperkeratosis on histology in a 3-year-old boy for the rarity of the entity.

Case Report

A 3-year-old boy, the only child of a non-consanguineous parentage, presented with widespread warty eruption all over the body including the genitalia but sparing the scalp, face and palms and soles. The eruption began when the child was 3 weeks’ of age with lesions appearing first symmetrically over anterior thigh, and then over the axillae, and within a period of about 6 months progressed to attain the present distribution. There was no history of blisters or generalized redness at or after birth. The eruption tended to improve during summer with exacerbations in winter. The child had otherwise been in good health. There was no history of any developmental delay or visual or hearing difficulty. There was no significant family history.

Examination showed multiple, bilaterally symmetrical, verrucous plaques along the lines of Blaschko extensively involving the trunk and extremities [Figure 1]. The linear plaques ran transversely over the trunk and longitudinally over the limbs [Figures 2 and 3]. Hairs, nails, and oral cavity were normal. Systemic examination revealed no abnormality. Histopathological examination of lesional biopsy showed hyperkeratosis, acanthosis and papillomatosis. Focal epidermolytic hyperkeratosis was evident in the form of perinuclear vacuolization of keratinocytes of the upper epidermis with coarse keratohyaline granules [Figure 4]. Based on the characteristic clinical and histopathological features, a diagnosis of bilateral, systematized epidermolytic verrucous epidermal nevus was made.

Figure 1

Bilaterally symmetrical verrucous plaques along the lines of Blaschko

Figure 2

Symmetrical, linear verrucous plaques along the lines of Blaschko over the buttock and back of thighs

Figure 3

Transversely arranged, bilaterally symmetrical linear verrucous plaques over the back

Figure 4

Histopathology showing massive hyperkeratosis and focal granular degeneration of the epidermis. H and E, ×100

Discussion

Epidermal nevi of all types are considered an expression of genetic mosaicism arising from somatic mutation in the affected skin but sparing the unaffected skin. The most common pattern of keratinizing epidermal nevi is verrucous epidermal nevus presenting as verrucous, serpiginous plaque following the lines of Blaschko. Systematized VEN may involve one half of the body (nevus unius lateris). Bilaterally symmetrical involvement is also called ichthyosis hystrix.

While there are many histologic variants of the epidermal nevus, most cases demonstrate variable degrees of hyperkeratosis, acanthosis, and papillomatosis. Rare histological variants include epidermolytic hyperkeratosis and variants resembling acrokeratosis verruciformis, verruca vulgaris, Darier disease, porokeratosis, seborrheic keratosis or psoriasis.[2] Identical histology of epidermolytic VEN and BIE results from a clone of cells expressing a mutation in one of the BIE genes KRT 1 and KRT 10 in the former.[345]

BIE, a rare autosomal dominant disorder, presenting as severe blisters and erythroderma at birth which usually subsides as the child grows and is replaced by appearance of thick, dark, hyperkeratotic skin especially on joints, apposed skin, scalp and neck for the rest of life. By analogy with BIE, patients of epidermolytic VEN are expected to be blistered at birth but they do not show such tendency,[1] which was also evident in our case. Epidermolytic VEN occurs sporadically and is not heritable, but a parent with such nevus may have gonadal mutation as well and can produce offspring with classical BIE.[3] Although VEN may be associated with cerebral and other internal manifestations in the form of ‘epidermal nevus syndrome’, epidermolytic variety is not associated with extracutaneous abnormalities as in our case as keratin genes are expressed only in the epithelia.

The clinical differentials of systematized epidermolytic VEN include non-epidermolytic VEN, verrucous stage of incontinentia pigmenti, ichthyosis bullosa of Siemens, and ichthyosis hystrix of Curth and Macklin. Incontinentia pigmenti produces systematized lesions along the lines of Blaschko and characteristically evolves through four clinical stages (bullous, verrucous, hyperpigmentation, and hypopigmentation) and exhibits eosinophilic spongiosis on histology. Ichthyosis bullosa of Siemens is caused by mutation of keratin 2 gene and may show mild phenotype of BIE. Hyperkeratosis occurs over joints, flexures, and dorsa of hands and feet. A characteristic feature is ‘Mauserung’ or ‘molting’: Superficial denuded areas with collarette-like borders.[6] Ichthyosis hystrix of Curth Macklin may show systematized rigid spiky hyperkeratosis and its histopathology exhibits non-specific features of hyperkeratosis, acanthosis, and papillomatosis without epidermolysis.[6]

The histological differential diagnoses of epidermolytic hyperkeratosis may include many conditions. The term ‘epidermolytic hyperkeratosis’ (EHK) refers to the combination of compact hyperkeratosis, perinuclear vacuolization of keratinocytes of the upper layers of epidermis, and coarse keratohyalin granules. These changes may occur incidentally in a large number of acquired benign and malignant conditions. However, only two congenital conditions besides BIE may show these changes: Ichthyosis bullosa of Siemens and epidermolytic palmoplantar keratoderma of Vorner. These could be eliminated by their characteristic clinical features.

Management of systematized VEN is mainly symptomatic. Associated bacterial overgrowth can be treated with antibacterial soaps and when necessary, oral antibiotics. Topical agents have a limited role and various agents had been used to decrease the hyperkeratosis. These include preparations containing salicylic acid, lactic acid, retinoic acid, 5-fluorouracil, calcipotriol and calcitriol.[1] Oral and topical retinoids have also been shown to improve patients with EHK although retinoids may promote desquamation and exacerbate blistering.[7] Continuous-wave carbon dioxide laser vaporization has been used with benefit for extensive VEN.[8] Patients with epidermolytic VEN are at risk of parenting a child with BIE. Thus, arrangements should be made to counsel the patient at a suitable age.[1]

What is new?

We reported a case of extensive, bilaterally symmetrical, systematized verrucous epidermal nevus of epidermolytic variety.