|Disease group||Keratinization disorders|
|DISEASE NAME||EPIDERMOLYTIC ICHTHYOSIS|
|Synonymous||Epidermolytic, Hyperkeratosis, Bullous Ichthyosiform Erythorderma, Bullous Congenital Ichthyosiform Erythroderma,
Bullous Erythroderma Ichthyosiformis Congenita of Brocq
|Estimated prevalence||< 1 / 200 000 to < 1 / 300 000|
|Gene (s)||KRT1 (139350), KRT10 (148040), KRT2|
In a consensus conference in 2009, a new classification system and terminology has been established for ichthyoses . Ichthyoses are determined as Mendelian disorders of cornification (MeDOC) that are characterized by universal scaling of the skin. In two main categories, non-syndromic forms (phenotype restricted to the skin) are distinguished from syndromic forms (involvement of other organs). A further distinction is made between common and rare forms. Within the non-syndromic forms the term keratinopathic ichthyosis is used as an umbrella term to describe all forms of ichthyosis that are based on mutations in keratin genes. The keratinopathic ichthyoses manifest at birth and sometimes involve blistering [2, 3].
Epidermolytic Ichthyosis (EI) is a rare keratinization disorder with blistering in its early phase, first described by Brocq in 1902 . It is usually inherited in an autosomal dominant fashion, but autosomal recessive cases have also been reported [5, 6]. Cases of postzygotic mosaicism are also described [7, 8]. EI is caused by mutations in the genes coding for KRT1 (12q13.13) or KRT10 (17q21.2) .
Infants are born with erythroderma, blistering and superficial erosions at sites of minor trauma. Hyperkeratosis most often develops later in early childhood . Yellow-brown, waxy and ridged scale builds up in skin creases, sometimes forming linear, spiny (hystrix) outgrowths. Over time, blister formation decreases and the ichthyosis worsens. Skin involvement is most often generalized, with palmoplantar involvement, but some patients have patchy or limited skin lesions. For neonates EI can be life threatening, due to secondary infections. EI persists in adulthood, with hyperkeratosis of variable intensity and extension .
Keratins 1 (type II) and 10 (type I) are co-expressed in the suprabasal layers of the epidermis during differentiation of keratinocytes. They are assembled together in specific pairs to form intermediate filaments. Mutations in the keratin 1 or 10 impair keratin filaments formation and weaken the structural stability of the keratinocyte cytoskeleton. This causes easy blistering, hyperproliferation, and hyperkeratosis .
Histopathology shows hypergranulosis with orthokeratosis, thickened stratum corneum, and cytolysis in the upper stratum spinosum and granular layers (epidermolytic hyperkeratosis). Electon microscopy shows tonofilament clumping in the supra basal layers of the epidermis. Molecular diagnosis is performed by sequencing the HIP and the HTP regions of the KRT1 and KRT10 genes.
Keratolytics (10% urea, 10% lactic acid) can improve localized hyperkeratotic lesions. Gentle debridement of scale is useful in palms and soles. The efficacy of emollients is limited. Oral retinoids are effective on hyperkeratosis , but they can worsen the skin fragiliy and must be used with caution because of their secondary effects. Low maintenance doses or intermittent treatments help preventing side effects. Antibiotic therapy is often required to treat secondary infection.
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Annales de dermatologie et de syphilographie, Paris. 1902, III: 1-31.
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