Ichtyoses

1 - ACKNOWLEDGEMENTS

Chapter written with the help of the EADV, the Fondation René Touraine and the Therapeutics in Dermatology

2 - OVERVIEW

Ichthyosis is a disorder of cornification, as it results from a disturbance of the formation of the outermost skin barrier (stratum corneum).

There are several disease variants, including inherited and acquired forms of ichthyosis. Disease prevalence varies widely, from 1:100–1:250 for ichthyosis vulgaris (the most common inherited form) to 1:200000–1:300000 for some rarer congenital ichthyoses.

Although the most severe disease forms may be life-threatening in the neonatal period, most people suffering from ichthyosis have a normal lifespan.

3 - SIGNS AND SYMPTOMS

Generically, ichthyosis is characterised clinically by persistently dry, thickened and diffusely scaling skin, with associated pruritus or even pain. The several types of ichthyosis have, however, significant differences regarding clinical manifestations and severity.

Patients with inherited ichthyoses may present with symptoms at birth or develop them later. Possible clinical presentations include:

• Dry skin with fine white scale: Patients with ichthyosis vulgaris usually have normal-appearing skin at birth, but develop this “fish scale” skin during early childhood. Skin involvement is diffuse, but skin folds are typically spared. Palmar lines are exaggerated. Atopic skin and other allergic diseases are common in these patients.
• Dry skin with polygonal greyish-brown scale: This is the usual presentation of recessive X-linked ichthyosis. Skin findings can be present at birth or develop in the first months of life. It is called “dirty-neck disease” due to prominent neck involvement.
• Blisters and erosions: In the so-called “keratinopathic ichthyoses”, skin is usually red (erythroderma) and moist at birth, with peeling and formation of blisters, that can rupture and give rise to skin erosions and/or infection. Later, generalised scaling and skin thickening ensue, especially over extensor joints.
• Collodion baby: Babies suffering from autosomal recessive congenital ichthyoses may be encased in a shiny membrane at birth, which later cracks (in days) and peels (in weeks), either being replaced by persistently lamellar scaling skin or “self-healing” (10% of cases). This is a life-threatening Dermatological emergency, that requires management in a neonatal intensive care unit.
• Harlequin baby: Babies suffering from harlequin ichthyosis, one of the autosomal recessive congenital ichthyoses, are usually born prematurely, encased in a yellowish, thick, armour-like skin, that impairs several vital functions like breathing and eating, limits closing of eyes (ectropion) and lips (eclabium), causes constrictions (e.g.: digit amputation), and facilitates infection. Harlequin ichthyosis is a severe form of disease, leading to the death of about half of afflicted babies. This life-threatening Dermatological emergency requires management in a neonatal intensive care unit.

Skin manifestations of acquired ichthyosis resemble those of ichthyosis vulgaris but begin in adulthood.

4 - WHO GETS AND CAUSES

Inherited ichthyoses are due to genetic mutations that affect the structure and function of skin cells of the stratum corneum. These ichthyoses can be further classified as “non-syndromic” or “syndromic”, depending on whether disease is limited to the skin or it also affects other organs, respectively. Non-syndromic inherited ichthyoses, which have several different transmission patterns within families, include ichthyosis vulgaris, recessive X-linked ichthyosis (affects males only), autosomal recessive congenital ichthyoses and keratinopathic ichthyoses. Syndromic ichthyoses include many complex diseases, like Netherton syndrome, Sjögren-Larsson syndrome and keratitis-ichthyosis-deafness (KID) syndrome.

Acquired ichthyosis encompasses the non-hereditary form of disease. Although its cause is yet unknown, some associations with systemic diseases and drugs have been identified, including:

• Hodgkin lymphoma and other cancers
• Hypothyroidism
• Sarcoidosis
• HIV infection / AIDS
• Nicotinic acid
• Anti-cancer drugs (particularly targeted therapies)
• Allopurinol
• Hydroxyurea

5 - DIAGNOSIS AND TREATMENT

Dermatologists can often diagnose this disorder clinically, but a skin biopsy is usually performed to confirm the diagnosis and the type of ichthyosis. Further diagnostic work-up, including genetic testing, may be warranted.

There is no cure for inherited ichthyoses. Severe disease forms, like “collodion baby” and “harlequin baby”, are life-threatening Dermatological emergencies requiring management in a neonatal intensive care unit, which includes placement in a high-humidity incubator, continuous clinical monitoring, nutritional and ventilatory support, careful skin care and prevention of infection. Treatment with systemic retinoids, like Acitretin and Isotretinoin, may be beneficial in severe forms. Vitamin D supplementation may be necessary in some cases.

Acquired ichthyosis usually resolves with treatment of the underlying disease or withdrawal of the causative drug.

General skin care measures recommended for patients with ichthyosis include:

• Use of non-soap cleansers
• Regular application of moisturising creams containing keratolytics (e.g.: urea, salicylic acid, glycolic acid, lactic acid)

6 - TIPS FOR MANAGING

Every patient with suspected ichthyosis should see a Dermatologist for adequate diagnosis and treatment.

Some skin functions may be persistently impaired in people suffering from ichthyosis, leading to increased water loss and deficient sweating and thermal regulation (heat intolerance). Dry, scaly skin may cause pruritus, pain and/or limit movements. Ichthyosis patients therefore require daily skin care, including regular application of moisturising creams containing keratolytics.

Secondary skin and/or systemic infections must be prevented and promptly treated.