Epidermolysis Bullosa Acquisita Clinical Presentation

Updated: Apr 29, 2016
  • Author: Daniel L Croom, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Most patients with epidermolysis bullosa acquisita (EBA) experience a slow onset and chronic disease that affects the trauma-prone extensor skin surfaces. The nature of the disease usually leads to skin fragility and secondary scarring that often causes restriction of mobility in the extensor skin surfaces.

In a subset of patients with inflammatory epidermolysis bullosa acquisita, the onset of disease is somewhat rapid and more widespread. In this group of patients, blisters occur in both trauma-prone and non–trauma-prone areas. Clinically, this phenotype resembles bullous pemphigoid or linear IgA bullous dermatosis.

In a subset of patients with predominant mucous membrane involvement, the disease manifests with blisters and scar formation in the oral, ocular, vaginal, and other mucous membranes, leading to significant dysfunction, such as visual function loss, dysphagia, malnutrition, or even mortality. The clinical phenotype of this subset of patients is indistinguishable from that of mucous membrane pemphigoid. In a published international consensus statement on mucous membrane pemphigoid, an expert panel decided to include this group of patients (previously designated as epidermolysis bullosa acquisita based in part on their autoantibodies to type VII collagen) in the category of mucous membrane pemphigoid.

The rationale for such inclusion is that this subset of patients has the clinical phenotype of mucous membrane pemphigoid and that the autoantibodies of patients with mucous membrane pemphigoid (as a group) target not a single, but multiple, skin basement membrane components, such as bullous pemphigoid antigen 2 (BP180), integrin beta-4 subunit, laminin-5, and laminin-6. Because this subset of patients cannot be distinguished from mucous membrane pemphigoid by clinical phenotype and autoantigen identity alone cannot be used to include or exclude a diagnosis of mucous membrane pemphigoid, it seems reasonable to include this subset of patients under the general category of mucous membrane pemphigoid.

Patients may have a medical history of inflammatory bowel disease, as it is associated with epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita has been reported to develop in a 73-year-old patient after a 2-week treatment of antibiotics.

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Physical

The skin and mucous membrane manifestations of epidermolysis bullosa acquisita (EBA) take several forms, including a noninflammatory or mildly inflammatory disease, a generalized inflammatory disease, and a predominant mucous membrane disease.

The noninflammatory or mildly inflammatory form, also known as classic epidermolysis bullosa acquisita, is most common and manifests as tense vesicles, bullae, and erosions primarily on trauma-prone areas, including the extensor surfaces of hands, knuckles, elbows, knees, and ankles. The blisters may be hemorrhagic. Blisters on mucous membranes rupture easily; the most common manifestation is erosions. This form of epidermolysis bullosa acquisita usually heals with significant scar and milia formation. Nail dystrophy and scarring alopecia also have been observed in some patients. This form clinically resembles porphyria cutanea tarda in elderly patients and the dominantly inherited form of epidermolysis bullosa dystrophica in children.

The generalized inflammatory form of epidermolysis bullosa acquisita presents with widespread, tense vesicles and bullae (some hemorrhagic) and is not localized to trauma-prone sites. Generalized erythema, urticarial plaques, and generalized pruritus may occur in some patients. This form of epidermolysis bullosa acquisita clinically resembles bullous pemphigoid or linear IgA bullous dermatosis. [14] The generalized inflammatory form usually heals with minimal scarring and milia formation.

A third variant of epidermolysis bullosa acquisita predominantly involves mucous membranes. Blisters and erosions of the buccal, conjunctival, gingival, palatal, nasopharyngeal, rectal, genital, and esophageal mucosae can occur. This variant clinically resembles mucous membrane pemphigoid and can result in significant mucosal scarring and dysfunction. An international consensus statement published in Archives of Dermatology (March 2002) reassigned this group of patients to the category of mucous membrane pemphigoid. [15]

Some patients with epidermolysis bullosa acquisita present with marked head and neck involvement, scarring, and minimal mucosal disease, which resembles the Brunsting-Perry variant of cicatricial pemphigoid.

A patient was reported to manifest with a localized form in periorbital areas. [16]

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Causes

Epidermolysis bullosa acquisita (EBA) is an autoimmune disease, manifested by autoantibodies that target type VII collagen, the major protein of anchoring fibrils and the one that connects the epithelial basement membrane to the dermis. Autoantibodies specific for type VII collagen alter the dermoepidermal junctional adhesion and lead to dermoepidermal separation. The initiating event that leads to autoantibody production is unknown.

Some evidence suggests a genetic predisposition to the disease. Epidermolysis bullosa acquisita affecting several family members has been reported. Additionally, black patients of African descent who develop epidermolysis bullosa acquisita have been found to have a genetic predisposition, owing to a link to HLA-DRB1*15:03. Most patients involved with this study had very atypical clinical presentations. In addition, immunogenetic studies revealed that most black patients from the southeastern part of the United States had an association with HLA-DR2. Subsequent studies on a larger population of white patients failed to reveal any statistically significant HLA allele associations with epidermolysis bullosa acquisita. [17]

Rarely, patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease, develop a generalized blistering skin disease with clinical and immunopathologic features of epidermolysis bullosa acquisita. These patients have a subepidermal blistering skin disease characterized by IgG, IgA, and C3 deposition at the skin basement membrane zone. Sera from these patients recognize the NC1 domain of type VII collagen, the same target antigen recognized by patients with epidermolysis bullosa acquisita. The fact that epidermolysis bullosa acquisita, an organ-specific autoimmune disease, can develop in patients who already have a systemic autoimmune disease suggests that systemic autoimmunity can provoke an organ-specific autoimmune disease. Alternatively, the nonspecific inflammatory process present in systemic lupus may induce the release and exposure of basement membrane antigens to autoreactive lymphocytes by a process termed epitope spreading, subsequently leading to autoimmunity against the epidermolysis bullosa acquisita antigen. [18]

Epidermolysis bullosa acquisita is also associated with Crohn disease, an inflammatory bowel disease characterized by T-cell infiltration in the small intestine. Type VII collagen is expressed in intestinal epithelial basement membranes. The association of epidermolysis bullosa acquisita and inflammatory bowel disease may have an immunologic basis. It has been observed that a significant number of patients with Crohn disease have circulating IgG autoantibodies that recognize the NC1 domain, as demonstrated by enzyme-linked immunosorbent assay (ELISA), although they do not have epidermolysis bullosa acquisita clinically. The presence of these autoantibodies may represent a preclinical epidermolysis bullosa acquisita phenomenon, induced by the release and exposure of intestinal type VII collagen to autoreactive lymphocytes because of epitope spreading caused by the inflammatory reaction in their gastrointestinal tract.

In some patients with epidermolysis bullosa acquisita and bullous SLE, circulating autoantibodies against other skin basement membrane components, such as bullous pemphigoid antigens, laminin-5, and laminin-6, in addition to type VII collagen, have been reported. These observations further support the role of epitope spreading. [15, 19, 20]

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