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
Contributor Information and Disclosures

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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