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The prevalence range of all types of KPI is estimated at 1/909,000 in France. The exact worldwide prevalence of epidermolytic ichthyosis (EI) is unknown but is in the 1/2,300,000-4,350,000 range in Japanese and Danish population studies.

Infants present at birth, or shortly after, with erythroderma, mild scaling, severe blistering, and superficial erosions at sites of trauma and flexural areas. Yellow-brown hyperkeratotic plaques, often with mild background erythroderma, develop in the first months of life. The skin has a characteristic dirty looking appearance. Hyperkeratosis has a ridged appearance along skin lines and a cobblestone pattern in the extensor surfaces of joints. It is most often generalized but may be limited to joint flexures, anterior neck, abdominal wall, and infragluteal folds, with relative sparing of the face. Over time, hyperkeratosis worsens and blister formation decreases but may still occur (following skin trauma or during summer). Palmoplantar involvement is seen in some patients and painful blisters tend to develop underneath. Digital contractures and pseudoainhum may occur. Skin is often itchy, smelly, and subject to infections. Other features may include hypohidrosis, scalp scaling, nail dystrophy and abnormal posture. Growth failure may be seen in severe cases. EI persists into adulthood, with hyperkeratosis of variable intensity and extension.

The disease is caused by mutations in the genes coding for epidermal suprabasal keratins 1 (KRT1; 12q13.13) and 10 (KRT10; 17q21-q23) that impair keratin intermediate filament formation in the suprabasal keratinocytes. A genotype-phenotype correlation exists, with palmoplantar involvement being generally associated with KRT1, as KRT10 is less expressed in these locations. The position of the mutation may influence the severity of the phenotype

Diagnosis is based on the clinical picture and on histological examination showing hyperkeratosis with orthokeratosis, hypergranulosis, and cytolysis in the upper stratum spinosum and granular layers with characteristic intracellular vacuolization (epidermolytic hyperkeratosis). Electron microscopy shows suprabasal keratinocytes with keratin intermediate filaments clumps and perinuclear keratin clumps in the upper epidermis. Genetic testing confirms the diagnosis.

Differential diagnosis at birth includes other blistering diseases: toxic epidermal necrolysis, inherited epidermolysis bullosa, staphylococcal scalded skin syndrome, incontinentia pigmenti or herpetic infection. In later stages, blistering, ridges along skin lines, and histologic features help to differentiate it from other forms of ichthyoses. Superficial EI usually has a milder phenotype, lacks keratoderma, and has areas with characteristic superficial scaling. Annular epidermolytic ichthyosis is distinguished by the polycyclic and intermittent lesions.

Genetic antenatal diagnosis is available.

The disease has an autosomal dominant mode of inheritance. Genetic counseling can be offered to affected families when a causing mutation has been identified.

Treatment is symptomatic. Emollients are often used but have limited efficacy. Topical keratolytics and mechanical removal of scales can improve hyperkeratotic lesions, but may worsen blistering. Some patient, especially those with KRT10 mutation, may benefit from low dose acitretin. Antiseptic washes reduce the bacterial colonization and body odor. Antibiotic therapy is required in cases of bacterial infection.

The severity of the disease is variable. EI impacts the quality of life and social interactions due to skin aspect, pain, walking difficulties, pruritus, body odor, infections, malnutrition and hand contractures. EI can be life-threatening during the neonatal period due to infections and/or dehydration.

Last update: February 2023 - Expert reviewer(s): Dr Eulalia BASELGA TORRES | ERN-Skin*

* European Reference Network