Epidermolysis bullosa acquisita (ORPHA:46487)
A rare, chronic, incurable, sub epithelial autoimmune bullous disease characterized by the presence of tissue bound autoantibodies against type VII collagen within the basement membrane zone of the dermal-epidermal junction of stratified squamous epithelia. The patient's serum may also have anti-type VII collagen autoantibodies. The clinical presentation is varied, and may involve the skin, oral mucosa and the upper third of the esophagus. The classical presentation is reminiscent of hereditary dystrophic epidermolysis bullosa (EB) with skin fragility, blisters and erosions and skin scarring. Other non-classical clinical presentations include an inflammatory bullous pemphigoid-like eruption, a mucous membrane pemphigoid-like eruption, and an IgA bullous dermatosis-like disease.
Epidemiology
The prevalence is unknown, but the incidence is estimated at 1/96,200 new cases per year.
Clinical description
Epidermolysis bullosa acquisita (EBA) is an acquired disease with onset typically in middle-aged adults but can rarely occur in childhood. The disease manifests in several possible ways. The classical presentation is reminiscent of hereditary dystrophic EB with skin fragility, blisters and erosions and skin scarring. There is marked skin fragility with skin blisters and erosions over trauma-prone areas of the skin that results in skin scarring. This form is relatively non-inflammatory. Mucous membrane lesions and nail dystrophy are common. A second possible clinical presentation is an inflammatory bullous eruption reminiscent of the autoimmune bullous disease, bullous pemphigoid. These bullae are on inflammatory plaques and may be flexural rather than over trauma-prone areas. A third possible clinical presentation is mucosal-centered with blisters, erosions and scarring of the conjunctival and oral mucosae, but may also involve the larynx and urethra. A fourth possible presentation is an IgA anti-type VII collagen mediated disease reminiscent of IgA bullous dermatosis and dermatitis herpetiformis. Diseases frequently associated with EBA include inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and systemic lupus erythematosus.
Etiology
EBA is caused by IgG autoantibodies generated against type VII collagen in the skin located at the dermal-epidermal junction. Type VII collagen is the major component of anchoring fibril structures located at the dermal-epidermal junction just beneath the lamina densa. These structures hold the epidermal and dermal layers of skin together. The autoantibodies against type VII collagen perturbs the function of anchoring fibrils and the adherence between these two main layers of skin is compromised and prone to blistering.
Diagnostic methods
Diagnosis is made by histology and direct immunofluorescence (DIF) of skin biopsies, salt-split skin DIF, indirect immunofluorescence (IIF) of patient's serum, salt-split skin IIF, immunoblotting of patient serum against type VII collagen, detection of anti-type VII collagen autoantibodies by ELISA and/or immune-electron microscopy of a skin biopsy.
Differential diagnosis
The differential diagnosis should include other subepidermal, autoimmune bullous diseases.
Management and treatment
In EBA patients without inflammatory bowel disease, oral colchicine is the first-line treatment. Dapsone may be helpful in some patients. Oral cyclosporine A controls the disease, but its nephrotoxic side-effects limit its use. In the classical form of EBA, other types of immunosuppressive therapy (such as systemic steroids, azathioprine, mycophenylate mofetil,) are often ineffective, but may be useful in the inflammatory varieties of EBA. Although further trials are necessary, encouraging results have been obtained with other approaches such as intravenous immunoglobulin therapy, extracorporeal photochemotherapy and, more recently, rituximab therapy.
Prognosis
EBA is a chronic, incurable disease that leads to dystrophic scarring and milia. During the disease course, the inflammatory forms may evolve to resemble the classical form and vice-versa. Although not fatal, the progressive scarring and involvement of the oral and ocular mucosae can be functionally disabling.

                            Last update: 
                            June 2019


                            - Expert reviewer(s): 
                            Pr David WOODLEY