The ichthyoses - Disorders of keratinization

The ichthyoses

The word ichthyosis comes from the Greek word for a fish. It is applied to disorders that share, as their main feature, a dry rough skin with marked scaling but no inflammation. Strictly speaking, the scales lack the regular overlapping pattern of fish scales, but the term is usefully descriptive and too well entrenched to be discarded. There are several types

Ichthyosis vulgaris

Cause

Inherited as an autosomal dominant disorder, this condition is common and affects about 1 person in The relevant gene may be concerned with the production of profilaggrin, a precursor of filaggrin, itself a component of keratohyalin granules.

Presentation

The dryness is usually mild and symptoms are few. The scales are small and branny, being most obvious on the limbs and least obvious in the major flexures. The skin creases of the palm may be accentuated. Keratosis pilaris  is often present on the limbs.

Clinical course

The skin changes are not usually present at birth but develop over the first few years of life. Some patients improve in adult life, particularly during warm weather, but the condition seldom clears completely.

Complications

The already dry skin chaps in the winter and is easily irritated by degreasing agents. This should be taken into account in the choice of a career. Ichthyosis of this type is apt to appear in a stubborn combination with atopic eczema.

Differential diagnosis

It can usually be distinguished from less common types of ichthyosis on the basis of the pattern of inheritance and of the type and distribution of the scaling.

Investigations

None are usually needed.

Treatment

This is palliative. The dryness can be helped by the regular use of emollients, which are best applied after a shower or bath. Emulsifying ointment, soft white paraffin, E45 and unguentum merck are all quite suit-able (Formulary 1) and the selection depends on the patient’s preference. Many find proprietary bath oils and creams containing urea or lactic acid helpful also (Formulary 1).

X-linked recessive ichthyosis

Cause

This less common type of ichthyosis is inherited as an X-linked recessive trait and therefore, in its complete form, is seen only in males, although some female carriers show mild scaling. The condition affects about 1 in 6000 males in the UK and is associated with a deficiency of the enzyme steroid sulphatase, which hydrolyses cholesterol sulphate. The responsible gene has been localized to the terminal part of the X chro-mosome at Xp 22.3.

Presentation and course

In contrast to the delayed onset of the dominantly inherited ichthyosis vulgaris, scaling appears early, often soon after birth, and always by the first birth-day. The scales are larger and browner (Fig. 4.1), involve the neck, and to a lesser extent the popliteal and antecubital areas, as well as the skin generally. The palms and soles are normal. There is no association with atopy or keratosis pilaris. The condition persists throughout life.

Complications

Corneal opacities may appear in adult life. Kallmann’s syndrome is caused by the deletion of a part of the X chromosome that includes the gene for X-linked recess-ive ichthyosis, which is therefore one of its features. Other features of this contiguous gene disorder are hypogonadism, anosmia and neurological defects.

Differential diagnosis

This is as for ichthyosis vulgaris. It is helpful to remember that only males are affected. Bear Kallmann’s syndrome in mind if there are other congenital abnormalities.

Investigations

None are usually needed. A few centres can measure steroid sulphatase in fibroblasts cultured from a skin biopsy.

Treatment

Oral aromatic retinoids are probably best avoided.

Topical measures are as for ichthyosis vulgaris.

Collodion baby (Fig. 4.2)

This is a description and not a diagnosis. The bizarre skin charges are seen at birth. At first the stratum corneum is smooth and shiny, and the skin looks as though it has been covered with cellophane or col-lodion. Its tightness may cause ectropion and feeding difficulties. The shiny outer surface is shed within a few days leaving behind, most often, a non-bullous ichthyosiform erythroderma, and less often a lamellar ichthyosis. 

Problems with temperature regulation and high water loss through the skin in the early days of life are best dealt with by the use of a high humidity incubator. Regular applications of a greasy emollient also limit fluid loss and make the skin supple. The much rarer ‘harlequin fetus’ is covered with thick fissured hyperkeratosis. Ectropion is extreme and most affected infants die early.

Lamellar ichthyosis and non-bullous ichthyosiform erythroderma

Understandably, these rare conditions have often been confused in the past. Both may be inherited as an autosomal recessive trait, and in both the skin changes at birth are those of a collodion baby . Later the two conditions can be distinguished by the finer scaling and more obvious redness of non-bullous ichthyosiform erythroderma. Both last for life and are sufficiently disfiguring for the long-term use of acitretin to be justifiable (Formulary 2). Lamellar ichthyosis shows genetic heterogeneity: the most severe type is caused by mutations in the gene for keratinocyte transglutaminase, an enzyme that cross-links the cornified cell envelope, lying on chromosome 14q11.2.

Epidermolytic hyperkeratosis (bullous ichthyosiform erythroderma)

This rare condition is inherited as an autosomal dominant disorder. Shortly after birth the baby’s skin becomes generally red and shows numerous blisters. The redness fades over a few months, and the tend-ency to blister also lessens, but during childhood a gross brownish warty hyperkeratosis appears, sometimes in a roughly linear form and usually worst in the flexures. The histology is distinctive: a thickened granular cell layer contains large granules, and clefts may be seen in the upper epidermis. The condition is caused by mutations in the genes (on chromosomes 12q13 and 17q21) controlling the production of keratins 1 and 10. A few patients with localized areas of hyperkeratosis with the same his-tological features have gonadal mosaicism, and so their children are at risk of developing the general-ized form of the disorder. Treatment is symptomatic and antibiotics may be needed if the blisters become infected. Acitretin  has helped in severe cases.

Other ichthyosiform disorders

Sometimes ichthyotic skin changes are a minor part of a multisystem disease, but such associations are very rare. Refsum’s syndrome, an autosomal recessive trait, is caused by deficiency of a single enzyme con-cerned in the breakdown of phytanic acid, which then accumulates in the tissues. The other features (retinal degeneration, peripheral neuropathy and ataxia) over-shadow the minor dryness of the skin.

Rud’s syndrome is an ichthyosiform erythrodermain association with mental retardation and epilepsy. In Netherton’s syndrome, brittle hairs, with a so-called‘bamboo deformity’, are present as well as a curious gyrate and erythematous hyperkeratotic eruption (ichthyosis linearis circumflexa). Other conditions are identified by confusing acronyms: IBIDS (also known as trichothiodystrophy) stands for Ichthyosis, Brittle hair, Impaired intelligence, Decreased fertility and Short stature; the KID syndrome consists of Keratitis, Ichthyosis and Deafness.

Acquired ichthyosis

It is unusual for ichthyosis to appear for the first time in adult life; but if it does, an underlying disease should be suspected. The most frequent is Hodgkin’s disease. Other recorded causes include other lymphomas, leprosy, sarcoidosis, malabsorption and a poor diet. The skin may also appear dry in hypothyroidism.