eMedicine Specialties > Dermatology > Pediatric Diseases

Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)

Author: Sidney B Smith, MD, Medical Director, Dermatologist, Dermatology, Dermacare Laser and Skin Care Clinics of Tri-Cities
Coauthor(s): Jeffrey B Smith, MD, Mohs Surgery, Kaiser Permanente, San Jose, CA
Contributor Information and Disclosures

Updated: Jan 24, 2007

Introduction

Background

Epidermolytic hyperkeratosis (EHK) also is termed bullous congenital ichthyosiform erythroderma. EHK 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 EHK) weakens the structural stability of the keratinocytes, causing easy blistering, hyperproliferation, and hyperkeratosis.

Frequency

United States

One case per 200,000-300,000 persons

International

Same as in United States

Mortality/Morbidity

  • Mortality is possible if sepsis or electrolyte imbalance is not treated properly during the neonatal period.
  • Morbidities include recurrent infection, sepsis, and electrolyte imbalance, which are possible during the neonatal period.

Race

No racial predilection is apparent.

Sex

No sex predilection is recognized.

Age

EHK is a lifelong condition with an onset at birth or in the neonatal period.

Clinical

History

EHK 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 EHK 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. 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 subtypes do not have severe palmoplantar involvement. Distinctions between the 3 NPS subtypes are based on different clinical presentations.
    • NPS-1 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 is similar to NPS-1. The only differences are a brown scale instead of a hystrix scale and a lack of gait abnormalities.
    • NPS-3 has no palmoplantar hyperkeratosis, no digital contractures, and is generalized in skin distribution similar to NPS-1 and NPS-2. In contrast, the palmoplantar surface in NPS-3 is hyperlinear, has minimal scale, and a thin white scale is most prominent on the trunk. Erythroderma is mild to moderate. NPS-3 may have gait abnormalities similar to NPS-1.
  • PS subtypes have severe palmoplantar involvement. The 3 subtypes are differentiated based on clinical presentations.
    • PS-1 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 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 has cerebriform palmoplantar surfaces, no digital contractures, a tan scale, generalized skin involvement, no erythroderma, neonatal blistering, and no gait abnormalities.

Causes

Defects in genes for keratin 1 and 10 are the cause of EHK. Defects in keratin 1 are associated with the PS variants; defects in keratin 10 are associated with the NPS variants.

More on Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)

Overview: Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Differential Diagnoses & Workup: Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Treatment & Medication: Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Follow-up: Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Multimedia: Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
References

References

  1. Bale SJ, DiGiovanna JJ. Genetic approaches to understanding the keratinopathies. Adv Dermatol. 1997;12:99-113; discussion 114. [Medline].

  2. DiGiovanna JJ, Bale SJ. Clinical heterogeneity in epidermolytic hyperkeratosis. Arch Dermatol. Aug 1994;130(8):1026-35. [Medline].

  3. 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].

  4. Kwak J, Maverakis E. Epidermolytic hyperkeratosis. Dermatol Online J. 2006;12(5):6. [Medline].

  5. 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].

  6. 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].

  7. 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].

  8. McGowan KA, Aradhya S, Fuchs H, et al. A mouse keratin 1 mutation causes dark skin and epidermolytic hyperkeratosis. J Invest Dermatol. May 2006;126(5):1013-6. [Medline].

  9. 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].

  10. 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].

  11. Smack DP, Korge BP, James WD. Keratin and keratinization. J Am Acad Dermatol. Jan 1994;30(1):85-102. [Medline].

Further Reading

Keywords

bullous congenital ichthyosiform erythroderma

Contributor Information and Disclosures

Author

Sidney B Smith, MD, Medical Director, Dermatologist, Dermatology, Dermacare Laser and Skin Care Clinics of Tri-Cities
Sidney B Smith, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey B Smith, MD, Mohs Surgery, Kaiser Permanente, San Jose, CA
Jeffrey B Smith, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Marjan Garmyn, MD, PhD, Professor, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium; Chair and Adjunct Head, Department of Dermatology, University of Leuven, Belgium
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.