Epidermal naevus

Author: Vanessa Ngan, Staff Writer, 2003.

What is an epidermal naevus?

An epidermal naevus (American spelling nevus) is due to an overgrowth of the epidermis (upper layers of the skin). Lesions are present at birth (50%) or develop during childhood (mostly in the first year of life). The abnormality arises from a defect in the ectoderm. This is the outer layer of the embryo that gives rise to epidermis and neural tissue.

Types of epidermal naevi

The skin lesions most often referred to as epidermal naevi are due to an overgrowth of keratinocytes (horny skin cells).

However, several other conditions are also characterised by benign overgrowth of the epidermis and its appendages (organoid naevi):

What causes epidermal naevi?

There are two copies of every gene, one derived from the individual's mother and the other from their father. It is thought that there are two populations of skin cells, containing either the mother's genes or the father's genes (mosaicism). If one of these populations of skin cells is abnormal it results in localised areas of thickened skin. Luckily, epidermal naevi very rarely affect more than one member of the family. Mutations have been detected in FGFR3, PIK3CA and HRAS in epidermal naevi.

Epidermal naevi are distributed along the lines of Blashko. These lines are the tracks taken by groups of genetically identical cells in the developing embryo. Skin cells that have the active abnormal gene spread out to form the epidermal naevus, whereas the remaining skin cells form the other areas of apparently normal skin.

New research has found point mutations in keratin genes that support this theory. The abnormal gene is found in the epidermal naevus cells but not in the normal skin. The same keratin 1 and keratin 10 gene abnormalities have been found in parents who have epidermolytic epidermal naevus and in their offspring who have bullous ichthyosiform erythroderma (a rare form of ichthyosis). So the epidermolytic epidermal naevus is thought to be a mosaic form of this type of ichthyosis.

The ATP2A2 gene abnormality that arises in Darier disease has been detected in the affected cells of a patient with acantholytic epidermal naevus, so this type may be a mosaic form of Darier disease. Linear porokeratosis may be a mosaic form of disseminated superficial actinic porokeratosis.

Features of epidermal naevi

Epidermal naevi usually arise on the trunk and limbs, and are uncommon on the face or scalp. The majority are linear epidermal naevi, i.e. they form a line, usually just on one side of the body (unilateral). When they first appear at birth or in infancy they are flat tan or brown marks but as the child ages they become thickened and often warty. The naevus may also become more extensive for a few years.

Another name for a linear epidermal naevus is naevus unis lateralis. Systematised epidermal naevi are less common and are sometimes known as ichthyosis hystrix. There are multiple lesions that usually arise in a swirled pattern, arising on one or both sides of the body. In some patients, there are also other congenital abnormalities, particularly of the skeleton and central nervous system (ENS).

On skin biopsy, the epidermal naevus shows increased thickness of the epidermis. The rare epidermolytic epidermal naevus subtype is characterised by a specific histological pattern called epidermolytic hyperkeratosis and resembles that seen in bullous ichthyosiform erythroderma. Acantholytic epidermal naevus has pathology that resembles Darier disease. Linear porokeratosis has pathology that resembles disseminated superficial actinic porokeratosis.

Epidermal naevus syndromes

The epidermal naevus syndromes refer to the association of an epidermal naevus with abnormalities in other organ systems derived from the embryonic ectoderm. These syndromes may involve the eyes, bones or nervous system. Many specific syndromes have been described.

The defect causing the skin lesions may also result in disorders of other internal organs such as the brain, eyes and skeleton. When multiple organs are involved the condition is referred to as an epidermal naevus syndrome (ENS). Named syndromes include:

CHILD syndrome (Congenital hemidysplasia with ichthyosiform naevus and limb defects) is strikingly one-sided and only affects females. The gene is carried on the X chromosome; it is lethal in males becaue they have only a single X chromosome (karyotype XY) whereas females carry a normal X chromosome as well (karyotype XX). The CHILD syndrome has been found to be due to a mutation in the NSDHL gene at Xq28, which encodes a gene in cholesterol biosynthetic pathway. The naevus may contain fat including foam cells described as ‘verruciform xanthoma’.

Proteus syndrome is characterised by overgrowth of many tissues affecting multiple sites on both sides of the body. The overgrowth may affect the skin (the epidermal naevus), blood vessels, fat, fibrous tissue, lungs, kidneys and other organs. Benign and malignant tumours can appear later in life. It affects males and females and is thought to be due to one or more abnormalities of a gene that regulates cell growth. In some cases mutations have been found in the PTEN tumour suppressor gene.

Epidermal naevus with bone cysts and hypophosphatemic rickets is the term used to describe a syndrome that may include:

Complications of epidermal naevi

Most epidermal naevi remain unchanged in adulthood and do not cause any problems. However, very rarely another tumour can arise within the lesion. This may be a harmless syringocystadenoma papilliferum, or a skin cancer (keratoacanthoma, basal cell carcinoma or squamous cell carcinoma).

Therefore, if a lump or sore appears within an epidermal naevus, arrange for it to be reviewed by your dermatologist. It may require a biopsy or cutting out.

Treatment of epidermal naevi

There is no real effective medical treatment for epidermal naevi. Topical calcipotriol may reduce the wartiness in some cases. If necessary, laser or surgical removal of naevi may be performed.

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