Abstract
Epidermolysis bullosa acquisita (EBA) is a blistering skin disease that is caused by an autoantibody to type VII collagen (C7). C7 is the main component of large structures called anchoring fibrils localized at the dermal-epidermal junction (DEJ) of skin and critical for epidermal – dermal adherence. Classically, EBA presents as a mechanobullous disease with skin fragility and scarring reminiscent of hereditary dystrophic epidermolysis bullosa (DEB) or porphyria cutanea tarda. Nevertheless, if the disease is defined as autoimmunity to type VII collagen, EBA can have clinical presentations that are reminiscent of inflammatory bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), and Brunsting-Perry pemphigoid. Very rarely, EBA involving IgA autoantibodies to C7 presents clinically similar to linear IgA bullous dermatosis (LABD) with small pruritic symmetrical papulovesicles. Anecdotal reports have linked EBA to several underlying systemic diseases with the most common being inflammatory bowel disease (IBD) and systemic bullous erythematosus (SLE). Interestingly, in the gastrointestinal track there is an anchoring fibril equivalent composed of C7, and patients with Crohn’s Disease and other IBDs have anti-C7 antibodies in their plasma. EBA is diagnosed using salt-split skin indirect and direct immunofluorescence (IIF and DIF), ELISA or Western blot analysis to detect anti-C7 antibodies in the blood, and, at research centers, by immuno-electron microscopy. EBA is notoriously difficult to treat. Systemic steroids and immunosuppressant agents (azathiaprine, mycophenolate mofetil, cyclophosphamide, and methotrexate) are inconsistently effective. Colchicine and cyclosporine may be helpful, but the former cannot be used in patients who have concomitant IBD and the latter requires very high doses. Other treatments with varying success include dapsone, photophoresis, IVIG and plasmapheresis. Recently, rituximab, an anti-CD20 monoclonal antibody, has shown promise in EBA.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- BMZ:
-
Basement membrane zone
- BP:
-
Bullous pemphigoid
- C7:
-
Collagen VII
- CBDC:
-
Chronic bullous disease of childhood
- CP:
-
Cicatricial pemphigoid
- CsA:
-
Cyclosporin A
- DEB:
-
Dystrophic epidermolysis bullosa
- DIF:
-
Direct immunofluorescence
- EB:
-
Epidermolysis bullosa
- EBA:
-
Epidermolysis bullosa acquisita
- ECP:
-
Extracorporeal photochemotherapy
- ELISA:
-
Enzyme-linked immunosorbent assay
- EM:
-
Electron microscopy
- GI:
-
Gastrointestinal
- HLA:
-
Human leukocyte antigen
- IBD:
-
Inflammatory bowel disease
- IEM:
-
Immunoelectron microscopy
- IgG:
-
Immunoglobulin G
- IIF:
-
Indirect immunofluorescence
- IVIG:
-
Intravenous immunoglobulin
- LABD:
-
Linear IgA bullous dermatosis
- mg/m2 :
-
Milligrams per square meter
- PCT:
-
Porphyria cutanea tarda
- SLE:
-
Systemic lupus erythematosus
- SSS:
-
Salt-split skin
- TNF-α:
-
Anti–tumor necrosis factor-α
- TPMT:
-
Thiopurine methyltransferase
References
Elliott G. Two cases of epidermolysis bullosa. J Cutan Genitourin Dis. 1895;13:10–8.
Roenigk Jr HH, Ryan JG, Bergfeld WF. Epidermolysis bullosa acquisita. Report of three cases and review of all published cases. Arch Dermatol. 1971;103(1):1–10.
Gibbs RB, Minus HR. Epidermolysis bullosa acquisita with electron microscopical studies. Arch Dermatol. 1975;111(2):215–20.
Kushniruk W. The immunopathology of epidermolysis bullosa acquisita. Can Med Assoc J. 1973;108(9):1143–6.
Nieboer C, Boorsma DM, Woerdeman MJ, Kalsbeek GL. Epidermolysis bullosa acquisita. Immunofluorescence, electron microscopic and immunoelectron microscopic studies in four patients. Br J Dermatol. 1980;102(4):383–92.
Yaoita H, Briggaman RA, Lawley TJ, Provost TT, Katz SI. Epidermolysis bullosa acquisita: ultrastructural and immunological studies. J Invest Dermatol. 1981;76(4):288–92.
Woodley DT, Briggaman RA, O’Keefe EJ, Inman AO, Queen LL, Gammon WR. Identification of the skin basement-membrane autoantigen in epidermolysis bullosa acquisita. N Engl J Med. 1984;310(16):1007–13.
Woodley DT, Burgeson RE, Lunstrum G, Bruckner-Tuderman L, Reese MJ, Briggaman RA. Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen. J Clin Invest. 1988;81(3):683–7.
Woodley DT, O’Keefe EJ, McDonald JA, Reese MJ, Briggaman RA, Gammon WR. Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen. J Clin Invest. 1987;79(6):1826–30.
Lapiere JC, Chen JD, Iwasaki T, Hu L, Uitto J, Woodley DT. Type VII collagen specifically binds fibronectin via a unique subdomain within the collagenous triple helix. J Invest Dermatol. 1994;103(5):637–41.
Chen M, Marinkovich MP, Veis A, Cai X, Rao CN, O’Toole EA, et al. Interactions of the amino-terminal noncollagenous (NC1) domain of type VII collagen with extracellular matrix components. A potential role in epidermal-dermal adherence in human skin. J Biol Chem. 1997;272(23):14516–22.
Ray TL, Levine JB, Weiss W, Ward PA. Epidermolysis bullosa acquisita and inflammatory bowel disease. J Am Acad Dermatol. 1982;6(2):242–52.
Gammon WR, Heise ER, Burke WA, Fine JD, Woodley DT, Briggaman RA. Increased frequency of HLA-DR2 in patients with autoantibodies to epidermolysis bullosa acquisita antigen: evidence that the expression of autoimmunity to type VII collagen is HLA class II allele associated. J Invest Dermatol. 1988;91(3):228–32.
Woodley D. Epidermolysis bullosa acquisita. Prog Dermatol. 1988;22:1–13.
Stewart MI, Woodley DT, Briggaman RA. Epidermolysis bullosa acquisita and associated symptomatic esophageal webs. Arch Dermatol. 1991;127(3):373–7.
Gammon WR, Briggaman RA, Woodley DT, Heald PW, Wheeler Jr CE. Epidermolysis bullosa acquisita--a pemphigoid-like disease. J Am Acad Dermatol. 1984;11:820–32.
Provost TT, Maize JC, Ahmed AR, Strauss JS, Dobson RL. Unusual subepidermal bullous diseases with immunologic features of bullous pemphigoid. Arch Dermatol. 1979;115(2):156–60.
Richter BJ, McNutt NS. The spectrum of epidermolysis bullosa acquisita. Arch Dermatol. 1979;115(11):1325–8.
Dahl MG. Epidermolysis bullosa acquisita--a sign of cicatricial pemphigoid? Br J Dermatol. 1979;101(4):475–84.
Kurzhals G, Stolz W, Meurer M, Kunze J, Braun-Falco O, Krieg T. Acquired epidermolysis bullosa with the clinical feature of Brunsting-Perry cicatricial bullous pemphigoid. Arch Dermatol. 1991;127(3):391–5.
Tanaka N, Dainichi T, Ohyama B, et al. A case of epidermolysis bullosa acquisita with clinical features of Brunsting-Perry pemphigoid showing an excellent response to colchicine. J Am Acad Dermatol. 2009;61:715–9.
Hashimoto T, Ishiko A, Shimizu H, et al. A case of linear IgA bullous dermatosis withIgA anti-type VII collagen autoantibodies. Br J Dermatol. 1996;134:336–9.
Bauer JW, Schaeppi H, Metze D, Muss W, Pohla-Gubo G, Hametner R, et al. Ocular involvement in IgA-epidermolysis bullosa acquisita. Br J Dermatol. 1999;141(5):887–92.
Park SB, Cho KH, Youn JL, Hwang DH, Kim SC, Chung JH. Epidermolysis bullosa acquisita in childhood--a case mimicking chronic bullous dermatosis of childhood. Clin Exp Dermatol. 1997;22(5):220–2.
Callot-Mellot C, Bodemer C, Caux F, Bourgault-Villada I, Fraitag S, Goudie G, et al. Epidermolysis bullosa acquisita in childhood. Arch Dermatol. 1997;133(9):1122–6.
Lee CW. Serum IgA autoantibodies in patients with epidermolysis bullosa acquisita: a high frequency of detection. Dermatology. 2000;200:83–4.
Edwards S, Wakelin SH, Wojnarowska F, Marsden RA, Kirtschig G, Bhogal B, et al. Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis, and immunopathology in 11 children. Pediatr Dermatol. 1998;15(3):184–90.
Burke WA, Briggaman RA, Gammon WR. Epidermolysis bullosa acquisita in a patient with multiple endocrinopathies syndrome. Arch Dermatol. 1986;122(2):187–9.
Chan L, Woodley D. Pemphigoid: bullous and cicatricial. In: Lichenstein L, Fauci AS, editors. Rheumatology. 5th ed. St. Louis: Mosby; 1996. p. 93.
Chen M, O’Toole EA, Sanghavi J, Mahmud N, Weir D, Kelleher D, Fairley JA, Woodley DT. The EBA antigen is present in human colon and patients with Crohn’s disease have auto-antibodies to type VII collagen. J Invest Dermatol. 2002;118:1059–64.
Ishii N, Recke A, Mihai S, Hirose M, Hashimoto T, Zillikens D, et al. Autoantibody-induced intestinal inflammation and weight loss in experimental epidermolysis bullosa acquisita. J Pathol. 2011;224(2):234–44.
Vodegel RM, Jonkman MR, Pas HH, de Jong MC. U-serrated immunodeposition pattern differentiates type VII collagne targeting bullous diseases from other subjepidermal bullous autoimmune diseases. Br J Dermatol. 2004;151:112–8.
Woodley D, Sauder D, Talley MJ, Silver M, Grotendorst G, Qwarnstrom E. Localization of basement membrane components after dermal-epidermal junction separation. J Invest Dermatol. 1983;81(2):149–53.
Gammon WR, Briggaman RA, Inman 3rd AO, Queen LL, Wheeler CE. Differentiating anti-lamina lucida and anti-sublamina densa anti-BMZ antibodies by indirect immunofluorescence on 1.0 M sodium chloride-separated skin. J Invest Dermatol. 1984;82(2):139–44.
Gammon WR, Kowalewski C, Chorzelski TP, Kumar V, Briggaman RA, Beutner EH. Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J Am Acad Dermatol. 1990;22(4):664–70.
Domloge-Hultsch N, Anhalt GJ, Gammon WR, Lazarova Z, Briggaman R, Welch M, et al. Antiepiligrin cicatricial pemphigoid. A subepithelial bullous disorder. Arch Dermatol. 1994;130(12):1521–9.
Goletz S, Hashimoto T, Zillikens D, Schmidt E. Anti-p200 pemphigoid. J Am Acad Dermatol. 2014;71(1):185–91.
Chan LS, Wang XS, Lapiere JC, Marinkovich MP, Jones JC, Woodley DT. A newly identified 105-kD lower lamina lucida autoantigen is an acidic protein distinct from the 105-kD gamma 2 chain of laminin-5. J Invest Dermatol. 1995;105(1):75–9.
Ghohestani RF, Hudson BG, Claudy A, Uitto J. The alpha 5 chain of type IV collagen is the target of IgG autoantibodies in a novel autoimmune disease with subepidermal blisters and renal insufficiency. J Biol Chem. 2000;275(21):16002–6.
Ghohestani RF, Rotunda SL, Hudson B, Gaughan WJ, Farber JL, Webster G, et al. Crescentic glomerulonephritis and subepidermal blisters with autoantibodies to α5 and α6 chains of type IV collagen. Lab Invest. 2003;83:605–11.
Gammon WR, Woodley DT, Dole KC, Briggaman RA. Evidence that anti-basement membrane zone antibodies in bullous eruption of systemic lupus erythematosus recognize epidermolysis bullosa acquisita autoantigen. J Invest Dermatol. 1985;84(6):472–6.
Chen M, Chan LS, Cai X, O’Toole EA, Sample JC, Woodley DT. Development of an ELISA for rapid detection of anti-type VII collagen autoantibodies in epidermolysis bullosa acquisita. J Invest Dermatol. 1997;108(1):68–72.
Woodley DT, O’Keefe EJ, Reese MJ, Mechanic GL, Briggaman RA, Gammon WR. Epidermolysis bullosa acquisita antigen, a new major component of cutaneous basement membrane, is a glycoprotein with collagenous domains. J Invest Dermatol. 1986;86(6):668–72.
Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita. Cochrane Database Syst Rev. 2003;(1):CD004056.
Cunningham BB, Kirchmann TT, Woodley D. Colchicine for epidermolysis bullosa acquisita. J Am Acad Dermatol. 1996;34:781–4.
Mekori YA, Chowers Y, Ducker I, Klajman A. Inhibition of delayed hypersensitivity reactions by colchicine. II. Colchicine inhibits interferon-gamma induced expression of HLA-DR on gut epithelial cell line. Clin Exp Immunol. 1989;78(2):230–2.
Connolly SM, Sander HM. Treatment of epidermolysis bullosa acquisita with cyclosporine. J Am Acad Dermatol. 1987;16(4):890.
Crow LL, Finkle JP, Gammon WR, Woodley DT. Clearing of epidermolysis bullosa acquisita with cyclosporine. J Am Acad Dermatol. 1988;19:937–42.
McKinley SK, Huang JT, Tan J, Kroshinsky D, Gellis S. A case of recalcitrant epidermolysis bullosa acquisita responsive to rituximab therapy. Pediatr Dermatol. 2014;31(2):241–4.
Hughes AP, Callen JP. Epidermolysis bullosa acquisita responsive to dapsone therapy. J Cutan Med Surg. 2001;5:397–9.
Saha M, Cutler T, Bhogal B, Black MM, Groves RW. Refractory epidermolysis bullosa acquisita: successful treatment with rituximab. Clin Exp Dermatol. 2009;34:e979–80.
Li Y, Foshee JB, Sontheimer RD. Sustained clinical response to rituximab in a case of life-threatening overlap subepidermal autoimmune blistering disease. J Am Acad Dermatol. 2011;64(4):773–8.
Sadler E, Schafleitner B, Lanschuetzer C, Laimer M, Pohla-Gubo G, Hametner R, et al. Treatment-resistant classical epidermolysis bullosa acquisita responding to rituximab. Br J Dermatol. 2007;157:417–9.
Crichlow SM, Mortimer NJ, Harman KE. A successful therapeutic trial of rituximab in the treatment of a patient with recalcitrant, high-titre epidermolysis bullosa acquisita. Br J Dermatol. 2007;156:194–6.
Schmidt E, Benoit S, Brocker EB, Zillikens D, Goebeler M. Successful adjuvant treatment of recalcitrant epidermolysis bullosa acquisita with anti-CD20 antibody rituximab. Arch Dermatol. 2006;142(2):147–50.
Niedermeier A, Eming R, Pfutze M, Neumann CR, Happel C, Reich K, et al. Clinical response of severe mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption and rituximab (anti-CD20 monoclonal antibodies). Arch Dermatol. 2007;143(2):192–8.
Gordon KB, Chan LS, Woodley DT. Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy. Br J Dermatol. 1997;136(3):415–20.
Miller JL, Stricklin GP, Fine JD, King LE, Arzubiaga MC, Ellis DL. Remission of severe epidermolysis bullosa acquisita induced by extracorporeal photochemotherapy. Br J Dermatol. 1995;133(3):467–71.
Furue M, Iwata M, Yoon HI, Kubota Y, Ohto H, Kawashima M, et al. Epidermolysis bullosa acquisita: clinical response to plasma exchange therapy and circulating anti-basement membrane zone antibody titer. J Am Acad Dermatol. 1986;14:873–8.
Sami N, Ahmed AR. Results of intravenous immunoglobulin therapy in ocular involvement in epidermolysis bullosa acquisita. Invest Ophthalmol Vis Sci. 2003;44:1388.
Kim JH, Kim YH, Kim SC. Epidermolysis bullosa acquisita: a retrospective clinical analysis of 30 cases. Acta Derm Venereol. 2011;91:307–12.
Harman KE, Black MM. High-dose intravenous immune globulin for the treatment of autoimmune blistering diseases: an evaluation of its use in 14 cases. Br J Dermatol. 1999;140:864–74.
Caldwell JB, Yancey KB, Engler RJ, et al. Epidermolysis bullosa acquisita: efficacy of high-dose intravenous immunoglobulins. J Am Acad Dermatol. 1994;31:827–8.
Gourgiotou K, Exadaktylou D, Aroni K, Rallis E, Nicolaidou E, Paraskevakou H, Katsambas AD. Epidermolysis bullosa acquisita: treatment with intravenous immunoglobulins. J Eur Acad Dermatol Venereol. 2002;16:77–88.
Osada S-I, Yoshida R, Kikuchi I, Tsuruta D, Ansai S-I, Hashimoto T, Kawana S. Successful treatment of intravenous immunoglobulins in a patient with intractable epidermolysis bullosa acquisita with autoantibodies to type VII collagen and laminin alpha-3. J Clin Exp Dermatol Res. 2013;4:1–3.
Meier F, Sonnichsen K, Schaumburg-Lever G, Dopfer R, Rassner G. Epidermolysis bullosa acquisita: efficacy of high-dose intravenous immunoglobulins. J Am Acad Dermatol. 1993;29:334–7.
Ahmed AR, Gurcan HM. Treatment of epidermolysis bullosa acquisita with intravenous immunoglobulin in patients non-responsive to conventional therapy: clinical outcome and post-treatment long-term follow-up. J Eur Acad Dermatol Venereol. 2012;26:1074–83.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Lai, O.Y., Kasperkiewicz, M., DeClerck, B.K., Chen, M., Woodley, D.T. (2016). Epidermolysis Bullosa Acquisita. In: Sami, N. (eds) Autoimmune Bullous Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-26728-9_8
Download citation
DOI: https://doi.org/10.1007/978-3-319-26728-9_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-26726-5
Online ISBN: 978-3-319-26728-9
eBook Packages: MedicineMedicine (R0)