Epidermolysis Bullosa Acquisita 

  • Author: Lawrence S Chan, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Nov 15, 2011
 

Background

Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune subepidermal blistering disease of the skin and mucus membranes. Epidermolysis bullosa acquisita is characterized clinically by blisters, scars, and milia primarily at the trauma-prone areas. However, a subset of epidermolysis bullosa acquisita patients has a generalized inflammatory skin blister phenotype. Immunologically, epidermolysis bullosa acquisita is characterized by the presence of immunoglobulin G (IgG) autoantibodies (in most patients) targeting the noncollagenous (NC1) domain of type VII collagen, the major component of anchoring fibrils that connect the basement membrane to dermal structures. A small group of patients demonstrated IgG autoantibodies to the central triple-helical (collagenous) domain of type VII collagen. However, a small subset of patients exhibited immunoglobulin A (IgA), rather than IgG, class autoantibodies that target the type VII collagen.

Epidermolysis bullosa acquisita is rare in humans. In animals, epidermolysis bullosa acquisita has been reported in dogs only. In canine epidermolysis bullosa acquisita, the IgG autoantibodies also target the type VII collagen noncollagenous (NC1) domain, which shares greater than 80% homology in amino acid sequence with the human NC1 domain.[1, 2]

Note the clinical trial, Establishment of the National Epidermolysis Bullosa Registry.

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Pathophysiology

Epidermolysis bullosa acquisita primarily involves the skin, but it also can affect mucus membranes. The trauma-prone areas of the skin, such as the extensor surfaces of elbows, knees, ankles, and buttocks, most commonly are affected.

IgG autoantibodies specific for anchoring fibrils (type VII collagen) of the skin basement membrane have a heterogeneous subclass and light chain composition, and their complement-activating capacities do not correlate with the inflammatory phenotype. It is hypothesized that autoantibodies and trauma are contributing factors to the disease process.[3, 4]

Passive transfer of antibodies raised in rabbits against mouse type VII collagen induced blister formation in mice, thus confirming the potential role of antitype VII collagen antibody in the pathogenesis of the disease. The failure to induce blisters in C5-deficient mice by these rabbit antimouse type VII collagen antibodies supports a role for complement activation in the disease pathogenesis.

Induction of an active model of autoimmunity against type VII collagen in a hairless mouse strain (SKH1) revealed that regulatory T cells, which have been identified for their ability to inhibit the development of autoimmune diseases, do not inhibit the development of autoantibodies against the self-protein mouse-type VII collagen.

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Epidemiology

Frequency

United States

Epidermolysis bullosa acquisita is a rare disease; its frequency of occurrence is not known.

International

Epidermolysis bullosa acquisita has been reported in Europe and Asia. Because epidermolysis bullosa acquisita is a rare disease, the frequency of occurrence in other countries is not known.

Mortality/Morbidity

Epidermolysis bullosa acquisita is a chronic inflammatory disease with periods of partial remissions and exacerbations. Mortality as a direct consequence of epidermolysis bullosa acquisita is rare; however, epidermolysis bullosa acquisita is relatively unresponsive to treatment and can cause significant morbidity. Adverse effects associated with the medications used to treat epidermolysis bullosa acquisita also are associated with significant morbidity.

  • The chronic inflammation and scar formation on patients' extensor surfaces can severely hinder the daily activities of patients.
  • Oropharyngeal mucus membrane involvement can lead to periodontal disease, oral mucosal erosions, and esophageal strictures, which limit oral intake, and supraglottic stenosis with airway compromise. Ocular involvement can lead to obstruction of nasolacrimal ducts, conjunctival scarring, and blindness.
  • The scarring nature of epidermolysis bullosa acquisita can lead to nail destruction and hair loss.

Race

The race distribution of epidermolysis bullosa acquisita is not known. In one of the largest patient groups (24 patients) followed by the authors, 19 were white and 5 were black. This distribution is roughly proportional to the general population of whites and blacks in the United States.

Black patients of African descent who develop epidermolysis bullosa acquisita have been found to have a genetic predisposition, due to a link to HLA-DRB1*15:03. Most patients involved with this study had very atypical clinical presentations. Additionally, high frequencies of epidermolysis bullosa acquisita significantly associated with the HLA-DR2 have already been reported in American blacks. Therefore, black patients with autoimmune bullous diseases should be screened for epidermolysis bullosa acquisita.[5]

Sex

The sex distribution of epidermolysis bullosa acquisita is not known. In the 24 patients followed by the authors, the male-to-female ratio is 1:1.4.

Age

Epidermolysis bullosa acquisita can occur at any age. Epidermolysis bullosa acquisita more frequently affects elderly persons; however, children with epidermolysis bullosa acquisita have been reported including one child with the onset of epidermolysis bullosa acquisita at age 3 months. Internationally, about 25 cases of childhood onset epidermolysis bullosa acquisita have been reported in the literature. In the 24 patients followed by the authors, the average age of onset was 53 years.

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Contributor Information and Disclosures
Author

Lawrence S Chan, MD  Dr Orville J Stone Professor of Dermatology, Head, Department of Dermatology, University of Illinois College of Medicine

Lawrence S Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Dermatological Association, American Medical Association, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois State Medical Society, Microcirculatory Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

David Woodley, MD  Co-Chair, Professor, Department of Medicine, Division of Dermatology, University of Southern California

David Woodley, MD is a member of the following medical societies: American Academy of Dermatology, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Physicians, American Federation for Medical Research, American Society for Clinical Investigation, New York Academy of Medicine, Society for Investigative Dermatology, and Southern Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Ponciano D Cruz Jr, MD  Vice-Chair, JB Shelmire Professor, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: RCTS Consulting fee Independent contractor; Mary Kay Cosmetics Honoraria Consulting; Galderma Grant/research funds Principal Investigator

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Edward F Chan, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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Direct immunofluorescence performed on perilesional skin biopsy specimen from a patient with epidermolysis bullosa acquisita detects a linear band of immunoglobulin G deposit along the dermoepidermal junction.
Indirect immunofluorescence performed on salt-split normal human skin substrate using serum from a patient affected with epidermolysis bullosa acquisita detects immunoglobulin G class circulating autoantibodies that bind to the dermal (base) side of the basement membrane.
 
 
 
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