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Epidermolysis Bullosa

  • Author: M Peter Marinkovich, MD; Chief Editor: William D James, MD  more...
 
Updated: Jan 08, 2014
 

Background

Epidermolysis bullosa (EB) is a group of inherited bullous disorders characterized by blister formation in response to mechanical trauma. Historically, epidermolysis bullosa subtypes have been classified according to skin morphology.[1, 2]

Recent discoveries of the molecular basis of epidermolysis bullosa have resulted in the development of new diagnostic tools, including prenatal and preimplantation testing. Based on a better understanding of the basement membrane zone (BMZ) and the genes responsible for its components, new treatments (eg, gene or protein therapy) may provide solutions to the skin fragility found in patients with epidermolysis bullosa.

Related articles include Epidermolysis Bullosa Acquisita and Epidermolysis Bullosa (pediatrics version).

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Pathophysiology

Epidermolysis bullosa is classified into 3 major categories, including (1) epidermolysis bullosa simplex (intraepidermal skin separation), (2) junctional epidermolysis bullosa (skin separation in lamina lucida or central BMZ), and (3) dystrophic epidermolysis bullosa (sublamina densa BMZ separation, as in the images below).

Dominantly inherited dystrophic epidermolysis bull Dominantly inherited dystrophic epidermolysis bullosa. The blistering in this disease often is localized and is characterized by scarring and milia in healed blister sites.
Dominantly inherited dystrophic epidermolysis bull Dominantly inherited dystrophic epidermolysis bullosa. This subtype, similar to other dystrophic and junctional epidermolysis bullosa subtypes, can result in nail dystrophy and loss.

Researchers have proposed a new category termed hemidesmosomal epidermolysis bullosa, which produces blistering at the hemidesmosomal level in the most superior aspect of the BMZ. Epidermolysis bullosa simplex usually is associated with little or no extracutaneous involvement, while the more severe hemidesmosomal, junctional, and dystrophic forms of epidermolysis bullosa may produce significant multiorgan system involvement.[3, 4]

Significant progress has been achieved in finding specific molecular therapies for epidermolysis bullosa, including protein and gene therapy. Type VII collagen and laminin-5 gene therapy have been proven effective through in vivo models. Type VII collagen protein therapy has similarly been shown to be effective in an in vivo model. Currently, these therapies are being extensively studied at the preclinical stage, in animal models.

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Epidemiology

Frequency

United States

Assuming that mild cases of epidermolysis bullosa simplex are reported only 10% of the time, the affected population in the United States is approximately 12,500 persons. According to a National Epidermolysis Bullosa Registry report,[5] 50 epidermolysis bullosa cases occur per 1 million live births. Of these cases, approximately 92% are epidermolysis bullosa simplex, 5% are dystrophic epidermolysis bullosa, 1% are junctional epidermolysis bullosa, and 2% are unclassified. Patients with hemidesmosomal epidermolysis bullosa probably constitute much less than 1% of total epidermolysis bullosa cases.

International

According to the National Epidermolysis Bullosa Registry,[5] the number of epidermolysis bullosa cases in Norway is 54 cases per million live births, in Japan is 7.8 cases per million live births, and in Croatia is 9.6 cases per million live births.

Mortality/Morbidity

Infancy is an especially difficult time for epidermolysis bullosa patients. Generalized blistering caused by any subtype may be complicated by infection, sepsis, and death. Severe forms of epidermolysis bullosa increase the mortality risk during infancy. Patients with the Herlitz or letalis form of junctional epidermolysis bullosa have the highest risk during infancy with an estimated mortality rate of 87% during the first year of life. In patients with epidermolysis bullosa that survive childhood, the most common cause of death is metastatic squamous cell carcinoma (SCC), as in the image below.

Recessively inherited dystrophic epidermolysis bul Recessively inherited dystrophic epidermolysis bullosa, squamous cell carcinoma

This skin cancer occurs specifically in patients with recessively inherited epidermolysis bullosa who most commonly are aged 15-35 years. In contrast, dominantly inherited epidermolysis bullosa simplex and dystrophic epidermolysis bullosa and milder forms of junctional epidermolysis bullosa may not affect a patient's life expectancy adversely.

One study reported that from 1979-2002, the overall age-adjusted annual mortality annual mortality rate from bullous skin diseases 0.103 death per 100,000 population (2000 US standard population).[6]

Age

Onset of epidermolysis bullosa is at birth or shortly after. The exception occurs in mild cases of epidermolysis bullosa simplex, which may remain undetected until adulthood or occasionally remain undiagnosed.

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Contributor Information and Disclosures
Author

M Peter Marinkovich, MD Associate Professor, Department of Dermatology and Program in Epithelial Biology, Stanford University Medical Center; Dermatology Service, VA Palo Alto Health Care System

M Peter Marinkovich, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jean Paul Ortonne, MD Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Ngoc Pham, MD, to the development and writing of this article.

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Epidermolysis bullosa simplex, Weber-Cockayne subtype. This mild bullous disease is characterized by localized blistering at sites of trauma such as the feet.
Epidermolysis bullosa simplex, Koebner subtype. Palmoplantar blistering and hyperkeratosis are noted.
Epidermolysis bullosa simplex, Koebner subtype. Close-up image shows hyperkeratotic papules and plaques on the palm.
Junctional epidermolysis bullosa, Herlitz subtype. This severe disease is characterized by generalized intralamina lucida blistering at birth, significant internal involvement, and a poor prognosis.
Dominantly inherited dystrophic epidermolysis bullosa. The blistering in this disease often is localized and is characterized by scarring and milia in healed blister sites.
Dominantly inherited dystrophic epidermolysis bullosa. This subtype, similar to other dystrophic and junctional epidermolysis bullosa subtypes, can result in nail dystrophy and loss.
Recessively inherited dystrophic epidermolysis bullosa pseudosyndactyly (mitten-hand deformity) of the hands and feet
Recessively inherited dystrophic epidermolysis bullosa, oral cavity blistering and scarring
Recessively inherited dystrophic epidermolysis bullosa, squamous cell carcinoma
Diagram illustrating the organization of the dermal epidermal basement membrane and level of disruption in epidermolysis bullosa subtypes
 
 
 
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