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Ichthyosis — from the Greek word “ichthy,” meaning “fish” — is a skin condition presenting with fish-like scale. It’s a disorder of cornification, encompassing a large group of skin diseases characterized by excessive scaling. Ichthyosis vulgaris and X-linked ichthyosis are by far the commonest forms, while epidermolytic hyperkeratosis, lamellar ichthyosis, congenital ichthyosiform erythroderma and harlequin fetus are rare and also much more severe.

Ichthyosis vulgaris

Ichthyosis vulgaris is an autosomal dominant disorder with variable penetrance. There’s likely more than one responsible gene, and filaggrin, a protein binding to keratin fibres in epidermal cells, is thought to play an important role. Ichthyosis vulgaris has a prevalence of 1 in 250 and is diagnosed in infancy to early childhood.

Clinical features

Although rarely present at birth, the disease most often appears during the first months of life, manifesting with dry scaling skin. The first sign is usually a fine, flaky, white, adherent scale on the trunk and extensor surfaces of the extremities, sparing skin folds and other areas that tend to be moist. Scales have a “pasted on” appearance, and they’re usually coarser, larger, thickened and adherent in the centre when the lower legs are involved. Palms and soles are often hyperkeratotic with prominent skin markings and painful, furrowed heels. Patients may complain of pruritus.

There can be seasonal variation with improvement in summer as humidity increases. Also, ichthyosis vulgaris tends to wane with age. The condition is associated with atopy (atopic dermatitis, asthma, hay fever) and keratosis pilaris (follicular accentuation). In fact, atopic dermatitis may be present in up to half of patients and tends to affect the flexures. Watch for complications such as secondary bacterial infection, and treat as needed.

Investigations

A number of skin diseases resemble ichthyosis vulgaris (see sidebar). There are no diagnostic tests available, but biopsy can help clarify the diagnosis, as the stratum granulosum tends to be absent in ichthyosis vulgaris.

X-linked recessive ichthyosis

X-linked recessive ichthyosis (XLRI) is a skin disease found in men and is caused by steroid sulfatase (STS) deficiency. Female carriers are asymptomatic, as the STS gene is found on the X chromosome. XLRI occurs in 1 per 2,000-6,000 male babies, and typically appears in the first few weeks after birth. When the fetus has XLRI, a low level of estrogen in the amniotic fluid — due to STS deficiency in the placenta — results in poor progression of labour; affected babies are therefore commonly born by C-section.

The deficiency in steroid sulfatase activity, which plays a key role in cholesterol synthesis, causes the buildup of cholesterol intermediates in the epidermis. This leads to impaired formation of the stratum corneum, i.e. the outermost layer of the epidermis, and decreased barrier function of the skin.

Clinical features

Initially, XLRI will present with exfoliation of large scales, generalized peeling and mild erythroderma. Later during infancy, patients develop large, prominent, brown, thick adherent scales that start on the posterior neck progressing to the sides. These scales often give the appearance that the child is unwashed. Brown to grey/white scales then advance symmetrically to involve the trunk and extensor surfaces of extremities. A fine, white scale may cover the scalp. Scales will be larger on the lower extremities, and involvement of preauricular areas can be pathognomonic. Flexural areas are less commonly affected. X-linked recessive ichthyosis spares the central face, palms and soles.

The condition often dramatically improves in summer. Although fine scalp scaling frequently resolves on its own, scaling in the other areas usually persist throughout life, gradually worsening. The differential diagnosis is similar as for ichthyosis vulgaris, but also includes Kallmann syndrome (Xp microdeletion syndrome) and Rud syndrome (submicroscopic deletions in the telomeric portion of Xp).

Complications

XLRI can be complicated by asymptomatic corneal opacities in up to 50% of patients, including some female carriers. These don’t affect vision and can be seen by slit lamp. Rarely, there may be green colour blindness. Another complication is cryptorchidism, occurring in 10-15% of affected individuals. There’s also a greater risk of testicular cancer, irrespective of testicular maldescent, and of hypogonadism.

Investigations

As with other forms of ichthyosis, a birth history including the condition of the skin at the time of delivery is helpful. As well, you should ask about age of onset and location of scales. Biopsy can help define the type of ichthyosis. If it’s XLRI, histology will reveal hyperkeratosis with a granular layer present, whereas in ichthyosis vulgaris, the granular layer is absent. With X-linked ichthyosis, there will also be large numbers of melanosomes in the stratum corneum.

Sterol sulfatase deficiency can be quantified by a number of methods. Serum lipoprotein electrophoresis reveals faster low-density lipoprotein migration with increasing cholesterol sulfate levels. Biochemical assays can also directly measure STS activity in keratinocytes, fibroblasts, leukocytes, and prenatally in amniocytes. Southern blot, fluorescent in-situ hybridization (FISH) and PCR may all be used to determine a genetic defect, even in the unborn child. Non-invasive methods of prenatal diagnosis also exist, such as the measurement of decreased estrogen levels in maternal urine with the presence of nonhydrolyzed sulfated steroids. Karyotyping and FISH analysis can detect X:Y translocations and X chromosome deletions.

Treatment

Acquired ichthyosis tends to resolve with treatment of the underlying disorder, but there’s no cure for the inherited form. Instead, therapy is aimed at symptom control. Moisturizers are key in improving dryness and scaling, so patients should use such products as part of their daily routine. They should apply them immediately after bathing while still wet, in order to seal in water. Moisturizers containing keratolytic agents (e.g. alpha-hydroxy, salicylic or lactic acid), urea or glycerin help remove excessive scale, but they may cause some stinging.

Mild cleansers are preferred to regular soap, and humidifiers may be helpful, especially in winter. Topical retinoids have been used with some success, but their use is limited by local irritation. Systemic retinoids, such as acitretin and isotretinoin, are options if the topical approach isn’t working and the patient seeks aggressive treatment. Relapses are common if therapy is stopped.

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