Disease group Keratinization disorders
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
OMIM 113800
Inheritance Autosomal dominant
Gene (s) KRT1 (139350), KRT10 (148040)



Epidermolytic Ichthyosis (EI) is a rare keratinization disorder with blistering at birth, first described by Brocq in 1902.1 It is inherited in an autosomal dominant fashion, but autosomal recessive cases have also been reported as well as cases of postzygotic mosaicism.2-5 EI is usually caused by mutations in the genes coding for KRT1 (12q13.13) or KRT10 (17q21.2).6 Due to mutations in keratin genes, EI belongs to the keratinopathic ichthyoses, that include superficial epidermolytic ichthyosis (SEI, OMIM #146800, KRT2 mutations) and congenital reticular ichthyosiform erythroderma (CRIE, OMIM #609165, KRT1 or KRT10 mutations).7

Clinical Description

Infants with EI are born with varying degree of erythroderma, blistering and superficial erosions at sites of minor trauma. Infections, sepsis and dehydration can complicate the clinical course in the neonatal / early infancy period. Hyperkeratosis becomes manifest in late infancy / early childhood. Yellow-brown, waxy and ridged scales build up preferentially in skin creases, sometimes forming linear, spiny (hystrix) outgrowths. With increasing age, blister formation decreases and ichthyosis worsens, commonly associated with pruritus, anhidrosis and painful fissuring. Skin involvement is most often generalized but some patients have patchy or very limited skin lesions. Mutations in KRT1 can cause palmoplantar keratoderma of varying severity (in severe forms with digital contractures affecting joint mobility) that rarely occurs in patients with KRT10 mutations.8,9



Keratins 1 (type II) and 10 (type I) are co-expressed in the suprabasal layers of the epidermis during differentiation of keratinocytes. Both are major constituents of the intermediate filament cytoskeleton. Mutations in KRT1/KRT10 impair keratin filaments formation and weaken the structural stability of the keratinocyte cytoskeleton causing easy blistering, hyperproliferation, and hyperkeratosis. Mutations at the beginning or end of the 1A rod domain of KRT1/10 are associated with a severe phenotype. Approximately 50% of cases of EI occur de novo due to spontaneous mutations.10


Histopathologic signs are different from other ichthyosis types. Typical features are 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 can be established by screening of the KRT1 and KRT10 genes (disease-related mutations are frequently mapped to the HIP and HTP region, two highly conserved amino acid sequences, of the central rod domain).11

The differential diagnosis between EI, CRIE and SEI can be difficult, since the phenotypes can vary in severity. Therefore, in patients with suspected EI, in which no mutation in the corresponding genes can be found, analysis of other keratin genes could be useful.​​​​


Treatment is symptomatic. In infants, skin trauma should be prevented to avoid new blister formation. Appropriate wound care and prevention of infection as well as adequate pain management is further important. Nutritional monitoring is frequently necessary to prevent electrolyte imbalances due to increased fluid losses and metabolic demands. Systemic antibiotics should be initiated, when skin infections are suspected or identified. Hyperkeratosis in children and adults can be treated with keratolytics (e.g. urea, lactic acid, glycerin - however, efficacy of emollients alone is limited) as well as mechanical debridement for localized hyperkeratotic lesions. In children, the use of higher concentration salicylic acid topical preparations should not be used because of the risk of systemic salicylism.

Oral retinoids are effective against hyperkeratosis, but they can worsen skin fragility, exacerbate blistering and thus should not be given in the early phase of this disease. Bathing 2-3 times a week, with salt or sodium bicarbonate added to the bath as well as antiseptic agents (e.g. antibacterial soaps, chlorhexidine, dilute sodium hypochlorite), may help to descale and reduce bacterial colonization. 




1.   Brocq L. Erythrodermie congenitale ichthyosiforme avec hyperepidermotrophie. Ann Derm Syph. 1902;3:1-31.
2.    Müller FB, Huber M, Kinaciyan T, et al. A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. Hum Mol Genet. 2006;15(7):1133-1141.
3.    Terheyden P, Grimberg G, Hausser I, et al. Recessive epidermolytic hyperkeratosis caused by a previously unreported termination codon mutation in the keratin 10 gene. J Invest Dermatol. 2009;129(11):2721-2723.
4.    Happle R, König A. Dominant traits may give rise to paired patches of either excessive or absent involvement. Am J Med Genet. 1999;84(2):176-177.
5.    Kiritsi D, Nanda A, Kohlhase J, et al. Extensive postzygotic mosaicism for a novel keratin 10 mutation in epidermolytic ichthyosis. Acta Derm Venereol. 2014;94(3):346-348.
6.    McLean WH, Eady RA, Dopping-Hepenstal PJ, et al. Mutations in the rod 1A domain of keratins 1 and 10 in bullous congenital ichthyosiform erythroderma (BCIE). J Invest Dermatol. 1994;102(1):24-30.

7.    Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol 2010; 63: 607–641.
8.    Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys. 2011;508(2):123-137.
9.    Putra PB, Radiono S, Danarti R. Generalized epidermolytic ichthyosis with palmoplantar hyperkeratosis. Dermatol Online J. 2021;27(2).

10.   Ross R, DiGiovanna JJ, Capaldi L, Argenyi Z, Fleckman P, Robinson-Bostom L. Histopathologic characterization of epidermolytic hyperkeratosis: a systematic review of histology from the National Registry for Ichthyosis and Related Skin Disorders. J Am Acad Dermatol 2008; 59: 86–90
11.  Terrinoni A, Didona B, Caporali S, et al. Role of the keratin 1 and keratin 10 tails in the pathogenesis of ichthyosis hystrix of Curth Macklin. PLoS One. 2018;13(4):e0195792.