eMedicine Specialties > Dermatology > Pediatric Diseases
Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Updated: Dec 2, 2009
Introduction
Background
Epidermolytic hyperkeratosis (EHK) also is termed bullous congenital ichthyosiform erythroderma. Epidermolytic hyperkeratosis is a rare autosomal dominant ichthyosis, yet a high frequency of spontaneous mutations (up to 50%) occurs. In 1902, Brocq first described it as bullous ichthyotic erythroderma to distinguish the entity from congenital ichthyotic erythroderma.
Pathophysiology
The defect is found in the genes for keratin 1 and keratin 10.
Keratins are divided into 2 classes including basic type II keratins and acidic type I keratins. Keratin 1 is one of the basic type II keratins found on chromosome 12; keratin 10 is one of the acidic type I keratins found on chromosome 17.
Keratins form intermediate filaments when both type I and type II keratins are present. This combination provides structural stability to keratinocytes. Keratins 1 and 10 are coexpressed and are involved in the suprabasilar differentiation of keratinocytes. A defect at this level (as in epidermolytic hyperkeratosis) weakens the structural stability of the keratinocytes, causing easy blistering, hyperproliferation, and hyperkeratosis.
Frequency
United States
The incidence of epidermolytic hyperkeratosis is 1 case per 200,000-300,000 persons.
International
The incidence of epidermolytic hyperkeratosis internationally is the same as it is in United States.
Mortality/Morbidity
- Mortality is possible in epidermolytic hyperkeratosis if sepsis or electrolyte imbalance is not treated properly during the neonatal period.
- Morbidities of epidermolytic hyperkeratosis include recurrent infection, sepsis, and electrolyte imbalance, which are possible during the neonatal period.
Race
No racial predilection is apparent for epidermolytic hyperkeratosis.
Sex
No sex predilection is recognized for epidermolytic hyperkeratosis.
Age
Epidermolytic hyperkeratosis is a lifelong condition with an onset at birth or in the neonatal period.
Clinical
History
Epidermolytic hyperkeratosis presents at birth or shortly thereafter as erythema, blistering, and/or peeling, but symptoms in some patients may ameliorate over time.
Physical
In 1994, DiGiovanna and Bale separated the various clinical presentations of epidermolytic hyperkeratosis into 2 primary types, including NPS (without severe palm/sole hyperkeratosis) and PS (with severe palm/sole hyperkeratosis) based on the presence or absence of severe palmoplantar hyperkeratosis.1 The 2 primary types were subdivided further into 3 subtypes each depending on the clinical presentations. Some of the subtypes have general involvement, while others are localized only.
- NPS epidermolytic hyperkeratosis subtypes do not have severe palmoplantar involvement. Distinctions between the 3 NPS epidermolytic hyperkeratosis subtypes are based on different clinical presentations.
- NPS-1 epidermolytic hyperkeratosis has normal palmoplantar surfaces, no digital contractures, a hystrix scale, a generalized skin distribution, no history of erythroderma, a positive history of blistering, and patients may have abnormal gait.
- NPS-2 epidermolytic hyperkeratosis is similar to NPS-1 epidermolytic hyperkeratosis. The only differences are a brown scale instead of a hystrix scale and a lack of gait abnormalities.
- NPS-3 epidermolytic hyperkeratosis has no palmoplantar hyperkeratosis, no digital contractures, and is generalized in skin distribution similar to NPS-1 epidermolytic hyperkeratosis and NPS-2 epidermolytic hyperkeratosis. In contrast, the palmoplantar surface in NPS-3 epidermolytic hyperkeratosis is hyperlinear, has minimal scale, and a thin white scale is most prominent on the trunk. Erythroderma is mild to moderate. NPS-3 epidermolytic hyperkeratosis may have gait abnormalities similar to NPS-1 epidermolytic hyperkeratosis.
- PS epidermolytic hyperkeratosis subtypes have severe palmoplantar involvement. The 3 subtypes are differentiated based on clinical presentations.
- PS-1 epidermolytic hyperkeratosis has smooth palmoplantar hyperkeratotic surfaces, no digital contractures, a localized distribution of skin involvement (limited flexural involvement, truncal sparing), no erythroderma, a localized blistering, and no gait abnormalities.
- PS-2 epidermolytic hyperkeratosis has smooth palmoplantar hyperkeratotic surfaces but has digital contractures, generalized skin involvement with hyperkeratosis most severe over the joints at both flexor and extensor surfaces, mild-to-moderate erythroderma, positive blistering, and may have gait abnormalities.
- PS-3 epidermolytic hyperkeratosis has cerebriform palmoplantar surfaces, no digital contractures, a tan scale, generalized skin involvement, no erythroderma, neonatal blistering, and no gait abnormalities.
The following are clinical images of epidermolytic hyperkeratosis lesions:
Causes
Defects in genes for keratin 1 and 10 are the cause of epidermolytic hyperkeratosis.2,3,4,5 Defects in keratin 1 are associated with the PS epidermolytic hyperkeratosis variants; defects in keratin 10 are associated with the NPS epidermolytic hyperkeratosis variants.
Epidermolytic hyperkeratosis is caused by mutations in either the KRT1 or KRT10 gene. Palmoplantar keratoderma is usually associated with KRT1 mutations; however, a girl with epidermolytic hyperkeratosis and palmoplantar keratoderma with the KRT10 mutation has been reported.6 A new mutation in the KRT10 gene, Glu445Lys at position 445, has been reported.7
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References
DiGiovanna JJ, Bale SJ. Clinical heterogeneity in epidermolytic hyperkeratosis. Arch Dermatol. Aug 1994;130(8):1026-35. [Medline].
Lacz NL, Schwartz RA, Kihiczak G. Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event. Int J Dermatol. Jan 2005;44(1):1-6. [Medline].
Math A, Frank J, Handisurya A, et al. Identification of a de novo keratin 1 mutation in epidermolytic hyperkeratosis with palmoplantar involvement. Eur J Dermatol. Sep-Oct 2006;16(5):507-10. [Medline].
McGowan KA, Aradhya S, Fuchs H, de Angelis MH, Barsh GS. A mouse keratin 1 mutation causes dark skin and epidermolytic hyperkeratosis. J Invest Dermatol. May 2006;126(5):1013-6. [Medline].
Muller FB, Huber M, Kinaciyan T, et al. A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. Hum Mol Genet. Apr 1 2006;15(7):1133-41. [Medline].
Morais P, Mota A, Baudrier T, et al. Epidermolytic hyperkeratosis with palmoplantar keratoderma in a patient with KRT10 mutation. Eur J Dermatol. Jul-Aug 2009;19(4):333-6. [Medline].
Betlloch I, Lucas Costa A, Mataix J, Perez-Crespo M, Ballester I. Bullous congenital ichthyosiform erythroderma: a sporadic case produced by a new KRT10 gene mutation. Pediatr Dermatol. Jul-Aug 2009;26(4):489-91. [Medline].
Rothnagel JA, Lin MT, Longley MA, et al. Prenatal diagnosis for keratin mutations to exclude transmission of epidermolytic hyperkeratosis. Prenat Diagn. Aug 1998;18(8):826-30. [Medline].
Kragballe K, Steijlen PM, Ibsen HH, et al. Efficacy, tolerability, and safety of calcipotriol ointment in disorders of keratinization. Results of a randomized, double-blind, vehicle-controlled, right/left comparative study. Arch Dermatol. May 1995;131(5):556-60. [Medline].
Kwak J, Maverakis E. Epidermolytic hyperkeratosis. Dermatol Online J. Sep 8 2006;12(5):6. [Medline].
Achar A, Naskar B, Laha R, Ray S. Epidcermolytic hyperkeratosis: a case report. J Indian Med Assoc. Mar 2009;107(3):171-2. [Medline].
Bale SJ, DiGiovanna JJ. Genetic approaches to understanding the keratinopathies. Adv Dermatol. 1997;12:99-113; discussion 114. [Medline].
Leigh IM, Lane EB. Mutations in the genes for epidermal keratins in epidermolysis bullosa and epidermolytic hyperkeratosis. Arch Dermatol. Dec 1993;129(12):1571-7. [Medline].
Smack DP, Korge BP, James WD. Keratin and keratinization. J Am Acad Dermatol. Jan 1994;30(1):85-102. [Medline].
Further Reading
Keywords
epidermolytic hyperkeratosis, bullous congenital ichthyosiform erythroderma




Overview: Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)