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.
Patients often report rapid blister formation, within several hours of localized skin trauma. A relatively minimal amount of trauma or skin irritation can spark the formation of a bullous lesion. These blisters may remain intact for several weeks, however, before rupturing or becoming hemorrhagic. [22]
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.
While many diagnoses have been linked anecdotally to epidermolysis bullosa acquisita, inflammatory bowel disease remains the only associated condition, with a reported incidence of 25% in patients with epidermolysis bullosa acquisita. [23, 24]
Epidermolysis bullosa acquisita has been reported to develop in a 73-year-old patient after a 2-week treatment of antibiotics.
Physical Examination
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 or mechanobullous 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. [25] 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. A key differentiating factor, however, is that the mucous membrane lesions of epidermolysis bullosa acquisita can remain intact for extended periods, as opposed to mucous membrane pemphigoid, in which the blisters are seldom appreciated because they have already been disrupted. [22]
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. [26]
It is important to remember that individual presentations of epidermolysis bullosa acquisita may adapt over the course of disease, changing from one manifestation to another. This has been seen specifically in patients who develop mucous membrane involvement over time. [27]
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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.
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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.
