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Epidermolysis bullosa acquisita
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Courtesy Iris Aronson
Epidermolysis bullosa acquisita (EBA) is an uncommon, chronic, autoimmune blistering disease affecting the skin and mucous membranes. The disorder affects patients of any age, and the skin lesions occur commonly at trauma-prone skin areas (in the non-inflammatory mechanobullous scarring subset) or widespread skin areas (in the generalized inflammatory non-scarring subset). Although IgG (or rarely IgA or IgM) class autoantibodies targeting the skin basement membrane component type VII collagen (anchoring fibrils) are major contributing factors, minor physical trauma also plays an important role in the blister development.
Management Strategy
EBA, particularly the non-inflammatory mechanobullous subset, is characteristically very refractory to conventional medical therapies. For an immune-mediated blistering disease associated with autoantibodies that target skin components, the obviously logical approach is to suppress the immune responses, thereby reducing the production and effect of the autoantibodies to their target skin component type VII collagen. Unfortunately, currently there is no target–specific medication available. Thus the presently available non-target–specific immunosuppressive medications not only suppress the immune responses against type VII collagen but also reduce the patient’s immune defense to pathogens, leading to a relative immunodeficiency. Therefore, when treating patients with this disease, every effort should be made to use antiinflammatory instead of immunosuppressant agents, to use the lowest possible doses of immunosuppressant for the shortest time frame, and to replace immunosuppressant with antiinflammatory medications whenever feasible. Because of its rarity, well-controlled clinical trials have not been performed for EBA. The therapeutic guidelines in this chapter are derived mainly from case reports of small groups or single patients. A commonly used start-up regimen consists of a systemic corticosteroid combined with either mycophenolate mofetil or dapsone or both as a corticosteroid-sparing agent. For adult patients without major medical problems, a combination of oral prednisone (1 mg/kg daily), mycophenolate mofetil (1–2 g daily), and dapsone (100–200 mg daily) can be initiated.
Other medications also reported to be beneficial for EBA are colchicine (1–2 mg daily); ciclosporin (5–9 mg/kg daily); i ntravenous immunoglobulin (IVIG) treatment (400 mg/kg daily); and extracorporeal photochemotherapy . Most recently, a monoclonal antibody against B-cell–specific target CD20, rituximab (usual dose 375 mg/m 2 body surface area, multiple doses), has been reported to be effective in several cases.
In addition, patients with EBA should avoid physical trauma as much as possible. Patients should be informed to care for open wounds promptly and to recognize local skin infection and seek medical attention when infection occurs .
Specific Investigations
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Epidermolysis bullosa acquisita: ultrastructural and immunologic studies
Yaoita H, Briggaman RA, Lawley TJ, et al. J Invest Dermatol 1981; 76: 288–92.
Identification of the skin basement-membrane autoantigen in epidermolysis bullosa acquisita
Woodley DT, Briggaman RA, O’Keefe EJ, et al. N Engl J Med 1984; 310: 1007–13.
Direct immunofluorescence typically detects linear IgG deposits at the dermoepidermal junction in all patients. Indirect immunofluorescence detects IgG circulating autoantibodies bound to the dermal side of salt-separated normal skin substrate in approximately 50% of patients.
Development of an ELISA for rapid detection of antitype VII collagen autoantibodies in epidermolysis bullosa acquisita
Chen M, Chan LS, Cai X, et al. J Invest Dermatol 1997; 108: 68–72.
ELISA using recombinant protein of the non-collagenous (NC1) domain of human type VII collagen is the most sensitive and specific method for detecting IgG class circulating autoantibodies in patients.
Consensus on EBA diagnostic criteria International Bullous Diseases Group – Consensus on Diagnostic Criteria for Epidermolysis Bullosa Acquisita
Prost-Squarcioni C, Caux F, Schmidt E, et al. Br J Dermatol 2018; 179(1): 30–41. doi: 10.1111/bjd.16138 [Epub 2018 May 8].
In case circulating autoantibodies are not detected by indirect immunofluorescence (IIF) or ELISA methods, special techniques including transmission immune-EM, fluorescent overlay antigen mapping, or serration pattern analysis of direct IF are helpful in delineating the location of autoantibody target.
IgA-mediated epidermolysis bullosa acquisita: two cases and review of the literature
Vodegel RM, de Jong MC, Pas HH, et al. J Am Acad Dermatol 2002; 47: 919–25.
In rare incidences, IgA class rather than IgG class autoantibodies were found to target the type VII collagen, resulting in a clinical phenotype indistinguishable from the classic IgG-mediated disease. IgA-mediated disease, however, is less likely to form scars and is more responsive to dapsone treatment.
IgM-type epidermolysis bullosa acquisita
Omland SH, Gniadecki R. Br J Dermatol 2015; 173: 1566–8.
This is a very rare case where the targeting autoantibodies appear to be the IgM class.
Epidermolysis bullosa acquisita and inflammatory bowel disease
Raab B, Fretzin DF, Bronson DM, et al. JAMA 1983; 250: 1746–8.
Inflammatory bowel disease, particularly Crohn disease, is strongly associated with EBA. All patients should be questioned for symptoms of inflammatory bowel disease. If symptoms are present, a comprehensive gastrointestinal workup is indicated.
The epidermolysis bullosa acquisita antigen (type VII collagen) is present in human colon and patients with Crohn’s disease have autoantibodies to type VII collagen
Chen M, O’Toole EA, Sanghavi J, et al. J Invest Dermatol 2002; 118: 1059–64.
The presence of type VII collagen in the gut and autoantibodies to type VII collagen in patients with inflammatory bowel disease without skin manifestations supports an inflammation link between the gut and the skin.
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