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Dermatology > PEDIATRIC DISEASES
Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Article Last Updated: Jan 24, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Sidney B Smith, MD, Medical Director, Dermatologist, Dermatology, Dermacare Laser and Skin Care Clinics of Tri-Cities
Sidney B Smith is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Coauthor(s):
Jeffrey B Smith, MD, Mohs Surgery, Kaiser Permanente, San Jose, CA
Editors: Marjan Garmyn, MD, PhD, Professor, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium; Chair and Adjunct Head, Department of Dermatology, University of Leuven, Belgium; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center; 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; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
bullous congenital ichthyosiform erythroderma
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.
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.
Epidermolysis Bullosa
Ichthyosis, Lamellar
Ichthyosis, X-Linked
Staphylococcal Scalded Skin Syndrome
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Other Problems to be Considered
Ichthyosis bullosa of Siemens
Ichthyosis hystrix, Curth-Macklin type
Nonbullous ichthyosiform erythroderma
Lab Studies
- No general laboratory studies are needed, except if necessary to follow chosen therapy or bacterial culture for suspected infection. Keratin defect studies can be performed.
Procedures
- Along with clinical presentation and history, biopsies can be diagnostic in de novo cases.
- Keratin studies can be performed.
- Prenatal diagnosis can be made through analysis of chorionic villus sampling, amniotic cells, or fetal skin biopsies.
Histologic Findings
Hematoxylin and eosin findings are distinctive but not unique. Typical findings include marked hyperkeratosis, thick granular layer, coarse keratohyaline granules, and vacuolar degeneration of the upper dermis. Occasionally, deeper granular cells become dense, enlarged, and irregular, and the shaped masses appear to be keratohyaline granules. Electron microscopy findings show clumping of keratin filaments beginning at the suprabasal layer.
Medical Care
Correct diagnosis is the first step in this genodermatosis. Genetic counseling and prenatal diagnosis also can be offered.
Newborns with denuded skin are at increased risk for infection, secondary sepsis, and electrolyte imbalance. These newborns should be transferred to the neonatal ICU to be monitored and treated as needed.
Since the condition tends to improve with time, visits to the physician decrease. Wound care for blistering and aggressive moisturization/emollients are important.
Surgical Care
No surgical care is needed or recommended.
Consultations
- Refer patients who are considering conceiving children to a geneticist for reproductive concerns and assistance.
- Prenatal diagnosis can be made by ultrastructural analysis and by direct gene sequencing.
- Prenatal diagnosis of EHK can be performed by ultrastructural analysis of fetal skin biopsies and amniotic fluid cells. Keratin 1 and keratin 10 are expressed suprabasally as early as week 14 of gestation; normal fetal keratinization does not begin until the 24th week. To date, keratin filament aggregates have been detected for diagnostic purposes in the 19th week of gestation for diagnosis.
- Chorionic villus sampling can diagnose EHK earlier by direct gene sequencing if the familial mutation is known. The earliest documented diagnosis by this method is at the 15th week of gestation, but the chorionic villus sampling theoretically can be tested as early as the eighth week of gestation.
Diet
No special diet is needed.
Activity
Activity restrictions are not necessary.
No reported cure or specific therapy is available; however, reports of improvement have been noted with high-dose beta-carotene, systemic retinoids, topical retinoids, 10% glycerin, lactic acid, alpha-hydroxy acid, calcipotriol, antibacterial soap, and urea.
Further Inpatient Care
- Neonatal patients may need to be transferred to the NICU for monitoring of infection, sepsis, electrolyte imbalance, and administration of intravenous fluids or antibiotics.
Further Outpatient Care
- Schedule routine follow-up visits as needed for symptomatic relief or to follow laboratory studies during systemic therapies.
In/Out Patient Meds
- Inpatient medications are determined by clinical need to treat secondary effects of this condition (eg, sepsis, electrolyte imbalance).
- Outpatient medications are determined by what works best with each individual patient (see Medication).
Transfer
- Transfer of infants to the NICU to monitor for sepsis and electrolyte imbalance may be necessary.
Complications
- Patients are at an increased risk for recurrent infections, and a pungent smell can be noted.
Prognosis
- EHK is a lifelong condition. Some patients may experience amelioration of symptoms as they age.
Patient Education
- Educate patients concerning the potential of passing the chromosomal defect on to offspring.
Medical/Legal Pitfalls
- Failure to advise patients concerning the potential inheritance in offspring
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Pathology of epidermolytic hyperkeratosis (hematoxylin and eosin stain). |
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| Media file 4:
Pathology of epidermolytic hyperkeratosis (hematoxylin and eosin stain). |
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Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma) excerpt Article Last Updated: Jan 24, 2007
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