Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Epidermolysis bullosa acquisita

David T Woodley, MD
Mei Chen, PhD
Gene Kim, MD
Section Editor
John J Zone, MD
Deputy Editor
Abena O Ofori, MD


Epidermolysis bullosa acquisita (EBA) is a rare, sporadic, subepithelial, mucocutaneous blistering disease that usually develops in adulthood. EBA is classically described as a mechanobullous disorder characterized by skin fragility, noninflammatory tense bullae, milia, and scarring. Alternatively, EBA can present as an inflammatory bullous eruption reminiscent of bullous pemphigoid or other subepithelial autoimmune blistering diseases.

The pathogenesis of EBA involves the production of antibodies against type VII collagen, a major component of anchoring fibrils in the basement membrane zones of skin and mucosa (figure 1). The immune-mediated disruption of the anchoring fibrils likely contributes to cleavage within the basement membrane zone and clinical blistering.

The pathogenesis, clinical manifestations, and management of EBA will be discussed here. Hereditary epidermolysis bullosa is reviewed separately. (See "Epidemiology, pathogenesis, classification, and clinical features of epidermolysis bullosa" and "Diagnosis of epidermolysis bullosa" and "Overview of the management of epidermolysis bullosa".)


Although the name "epidermolysis bullosa acquisita" arose from the original view of EBA as a disorder reminiscent of recessive dystrophic epidermolysis bullosa (RDEB), EBA and epidermolysis bullosa are distinct diseases. RDEB is a hereditary disease that results from mutations in the COL7A1 gene that encodes type VII collagen. In contrast to EBA, RDEB usually first presents in infancy. (See "Diagnosis of epidermolysis bullosa".)


EBA is a rare disorder of uncertain incidence. Although pediatric cases have been reported, adults are most commonly affected [1-5]. Increased risks for EBA based upon gender, ethnicity, or geographic location have not been definitively established.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Sep 28, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Schmidt E, Höpfner B, Chen M, et al. Childhood epidermolysis bullosa acquisita: a novel variant with reactivity to all three structural domains of type VII collagen. Br J Dermatol 2002; 147:592.
  2. Callot-Mellot C, Bodemer C, Caux F, et al. Epidermolysis bullosa acquisita in childhood. Arch Dermatol 1997; 133:1122.
  3. Arpey CJ, Elewski BE, Moritz DK, Gammon WR. Childhood epidermolysis bullosa acquisita. Report of three cases and review of literature. J Am Acad Dermatol 1991; 24:706.
  4. Mayuzumi M, Akiyama M, Nishie W, et al. Childhood epidermolysis bullosa acquisita with autoantibodies against the noncollagenous 1 and 2 domains of type VII collagen: case report and review of the literature. Br J Dermatol 2006; 155:1048.
  5. Iranzo P, Herrero-González JE, Mascaró-Galy JM, et al. Epidermolysis bullosa acquisita: a retrospective analysis of 12 patients evaluated in four tertiary hospitals in Spain. Br J Dermatol 2014; 171:1022.
  6. Burgeson RE. Type VII collagen, anchoring fibrils, and epidermolysis bullosa. J Invest Dermatol 1993; 101:252.
  7. Sakai LY, Keene DR, Morris NP, Burgeson RE. Type VII collagen is a major structural component of anchoring fibrils. J Cell Biol 1986; 103:1577.
  8. Lapiere JC, Woodley DT, Parente MG, et al. Epitope mapping of type VII collagen. Identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa. J Clin Invest 1993; 92:1831.
  9. Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin 1993; 11:535.
  10. Jones DA, Hunt SW 3rd, Prisayanh PS, et al. Immunodominant autoepitopes of type VII collagen are short, paired peptide sequences within the fibronectin type III homology region of the noncollagenous (NC1) domain. J Invest Dermatol 1995; 104:231.
  11. Woodley DT, Briggaman RA, O'Keefe EJ, et al. Identification of the skin basement-membrane autoantigen in epidermolysis bullosa acquisita. N Engl J Med 1984; 310:1007.
  12. Gupta R, Woodley DT, Chen M. Epidermolysis bullosa acquisita. Clin Dermatol 2012; 30:60.
  13. Ray TL, Levine JB, Weiss W, Ward PA. Epidermolysis bullosa acquisita and inflammatory bowel disease. J Am Acad Dermatol 1982; 6:242.
  14. Kim JH, Kim YH, Kim S, et al. Serum levels of anti-type VII collagen antibodies detected by enzyme-linked immunosorbent assay in patients with epidermolysis bullosa acquisita are correlated with the severity of skin lesions. J Eur Acad Dermatol Venereol 2013; 27:e224.
  15. Sebaratnam DF, Murrell DF. Bullous systemic lupus erythematosus. Dermatol Clin 2011; 29:649.
  16. Christiano AM, Greenspan DS, Lee S, Uitto J. Cloning of human type VII collagen. Complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms. J Biol Chem 1994; 269:20256.
  17. Chen M, Kim GH, Prakash L, Woodley DT. Epidermolysis bullosa acquisita: autoimmunity to anchoring fibril collagen. Autoimmunity 2012; 45:91.
  18. Fukumoto T, Umekawa T, Higuchi M, et al. Childhood epidermolysis bullosa acquisita with autoantibodies against all 3 structural domains of type VII collagen. J Am Acad Dermatol 2004; 50:480.
  19. Tanaka H, Ishida-Yamamoto A, Hashimoto T, et al. A novel variant of acquired epidermolysis bullosa with autoantibodies against the central triple-helical domain of type VII collagen. Lab Invest 1997; 77:623.
  20. Chen M, Keene DR, Costa FK, et al. The carboxyl terminus of type VII collagen mediates antiparallel dimer formation and constitutes a new antigenic epitope for epidermolysis Bullosa acquisita autoantibodies. J Biol Chem 2001; 276:21649.
  21. Ishii N, Yoshida M, Hisamatsu Y, et al. Epidermolysis bullosa acquisita sera react with distinct epitopes on the NC1 and NC2 domains of type VII collagen: study using immunoblotting of domain-specific recombinant proteins and postembedding immunoelectron microscopy. Br J Dermatol 2004; 150:843.
  22. Ishii N, Yoshida M, Ishida-Yamamoto A, et al. Some epidermolysis bullosa acquisita sera react with epitopes within the triple-helical collagenous domain as indicated by immunoelectron microscopy. Br J Dermatol 2009; 160:1090.
  23. Christiano AM, Rosenbaum LM, Chung-Honet LC, et al. The large non-collagenous domain (NC-1) of type VII collagen is amino-terminal and chimeric. Homology to cartilage matrix protein, the type III domains of fibronectin and the A domains of von Willebrand factor. Hum Mol Genet 1992; 1:475.
  24. Chen M, Marinkovich MP, Veis A, 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; 272:14516.
  25. Vorobyev A, Ujiie H, Recke A, et al. Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters. J Invest Dermatol 2015; 135:1565.
  26. Woodley DT, Chang C, Saadat P, et al. Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita. J Invest Dermatol 2005; 124:958.
  27. Sitaru C, Mihai S, Otto C, et al. Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. J Clin Invest 2005; 115:870.
  28. Woodley DT, Ram R, Doostan A, et al. Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients. J Invest Dermatol 2006; 126:1323.
  29. Chen M, Marinkovich MP, Jones JC, et al. NC1 domain of type VII collagen binds to the beta3 chain of laminin 5 via a unique subdomain within the fibronectin-like repeats. J Invest Dermatol 1999; 112:177.
  30. Gammon WR, Briggaman RA, Woodley DT, et al. Epidermolysis bullosa acquisita--a pemphigoid-like disease. J Am Acad Dermatol 1984; 11:820.
  31. Gammon WR, Heise ER, Burke WA, et al. 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; 91:228.
  32. Luke MC, Darling TN, Hsu R, et al. Mucosal morbidity in patients with epidermolysis bullosa acquisita. Arch Dermatol 1999; 135:954.
  33. Ishii N, Furumura M, Hamada T, et al. Oesophageal involvement in epidermolysis bullosa acquisita. Br J Dermatol 2015; 172:288.
  34. Delgado L, Aoki V, Santi C, et al. Clinical and immunopathological evaluation of epidermolysis bullosa acquisita. Clin Exp Dermatol 2011; 36:12.
  35. Hoang-Xuan T, Robin H, Heller M, et al. Epidermolysis bullosa acquisita diagnosed by direct immunoelectron microscopy of the conjunctiva. Ophthalmology 1997; 104:1414.
  36. Shipman AR, Agero AL, Cook I, et al. Epidermolysis bullosa acquisita requiring multiple oesophageal dilatations. Clin Exp Dermatol 2008; 33:787.
  37. Medenica-Mojsilović L, Fenske NA, Espinoza CG. Epidermolysis bullosa acquisita. Direct immunofluorescence and ultrastructural studies. Am J Dermatopathol 1987; 9:324.
  38. Weinman D, Stewart MI, Woodley DT, Garcia G. Epidermolysis bullosa acquisita (EBA) and esophageal webs: a new association. Am J Gastroenterol 1991; 86:1518.
  39. Gammon WR, Briggaman RA, Wheeler CE Jr. Epidermolysis bullosa acquisita presenting as an inflammatory bullous disease. J Am Acad Dermatol 1982; 7:382.
  40. Dahl MG. Epidermolysis bullosa acquisita--a sign of cicatricial pemphigoid? Br J Dermatol 1979; 101:475.
  41. Hashimoto T, Ishiko A, Shimizu H, et al. A case of linear IgA bullous dermatosis with IgA anti-type VII collagen autoantibodies. Br J Dermatol 1996; 134:336.
  42. Rusenko KW, Gammon WR, Briggaman RA. Type VII collagen is the antigen recognized by IgA anti-sub lamina densa autoantibodies. J Invest Dermatol 1989; 92:510.
  43. Choi GS, Lee ES, Kim SC, Lee S. Epidermolysis bullosa acquisita localized to the face. J Dermatol 1998; 25:19.
  44. Kushniruk W. The immunopathology of epidermolysis bullosa acquisita. Can Med Assoc J 1973; 108:1143.
  45. Kurzhals G, Stolz W, Meurer M, et al. Acquired epidermolysis bullosa with the clinical feature of Brunsting-Perry cicatricial bullous pemphigoid. Arch Dermatol 1991; 127:391.
  46. Häfliger S, Klötgen HW, Horn M, et al. Erythrodermic Epidermolysis Bullosa Acquisita. JAMA Dermatol 2015; 151:678.
  47. Roenigk HH Jr, Ryan JG, Bergfeld WF. Epidermolysis bullosa acquisita. Report of three cases and review of all published cases. Arch Dermatol 1971; 103:1.
  48. Chan LS, Woodley DT. Pemphigoid: Bullous and cicatricial. In: Current Therapy in Allergy, Immunology and Rhematology, 5th ed, Lichtenstein LM, Fauci AS (Eds), Mosby, St Louis 1996. p.93.
  49. Chen M, O'Toole EA, Sanghavi J, et al. 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. J Invest Dermatol 2002; 118:1059.
  50. Ishii N, Recke A, Mihai S, et al. Autoantibody-induced intestinal inflammation and weight loss in experimental epidermolysis bullosa acquisita. J Pathol 2011; 224:234.
  51. Licarete E, Ganz S, Recknagel MJ, et al. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases. BMC Immunol 2012; 13:16.
  52. Ackerman AB, Chongchitnant N, Sanchez J, et al. Histologic diagnosis of inflammatory skin diseases: an algorithmic method based on pattern analysis, 2nd ed, Williams & Wilkins, Baltimore, MD 1997.
  53. Weedon D. The vesicobullous reaction pattern. In: Weedon's Skin Pathology, 3rd ed, Elsevier Limited, Edinburgh 2010. p.123.
  54. Palestine RF, Kossard S, Dicken CH. Epidermolysis bullosa acquisita: a heterogeneous disease. J Am Acad Dermatol 1981; 5:43.
  55. Smoller BR, Woodley DT. Differences in direct immunofluorescence staining patterns in epidermolysis bullosa acquisita and bullous pemphigoid. J Am Acad Dermatol 1992; 27:674.
  56. Yaoita H, Briggaman RA, Lawley TJ, et al. Epidermolysis bullosa acquisita: ultrastructural and immunological studies. J Invest Dermatol 1981; 76:288.
  57. Bauer JW, Schaeppi H, Metze D, et al. Ocular involvement in IgA-epidermolysis bullosa acquisita. Br J Dermatol 1999; 141:887.
  58. Vodegel RM, Jonkman MF, Pas HH, de Jong MC. U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases. Br J Dermatol 2004; 151:112.
  59. Terra JB, Meijer JM, Jonkman MF, Diercks GF. The n- vs. u-serration is a learnable criterion to differentiate pemphigoid from epidermolysis bullosa acquisita in direct immunofluorescence serration pattern analysis. Br J Dermatol 2013; 169:100.
  60. Wozniak K, Kazama T, Kowalewski C. A practical technique for differentiation of subepidermal bullous diseases: localization of in vivo-bound IgG by laser scanning confocal microscopy. Arch Dermatol 2003; 139:1007.
  61. Ghohestani RF, Nicolas JF, Rousselle P, Claudy AL. Diagnostic value of indirect immunofluorescence on sodium chloride-split skin in differential diagnosis of subepidermal autoimmune bullous dermatoses. Arch Dermatol 1997; 133:1102.
  62. Chen M, Chan LS, Cai X, et al. Development of an ELISA for rapid detection of anti-type VII collagen autoantibodies in epidermolysis bullosa acquisita. J Invest Dermatol 1997; 108:68.
  63. Saleh MA, Ishii K, Kim YJ, et al. Development of NC1 and NC2 domains of type VII collagen ELISA for the diagnosis and analysis of the time course of epidermolysis bullosa acquisita patients. J Dermatol Sci 2011; 62:169.
  64. Terra JB, Jonkman MF, Diercks GF, Pas HH. Low sensitivity of type VII collagen enzyme-linked immunosorbent assay in epidermolysis bullosa acquisita: serration pattern analysis on skin biopsy is required for diagnosis. Br J Dermatol 2013; 169:164.
  65. Komorowski L, Müller R, Vorobyev A, et al. Sensitive and specific assays for routine serological diagnosis of epidermolysis bullosa acquisita. J Am Acad Dermatol 2013; 68:e89.
  66. Wozniak K, Hashimoto T, Ishii N, et al. Fluorescence overlay antigen mapping using laser scanning confocal microscopy differentiates linear IgA bullous dermatosis from epidermolysis bullosa acquisita mediated by IgA. Br J Dermatol 2013; 168:634.
  67. Kazama T, Yamamoto Y, Hashimoto T, et al. Application of confocal laser scanning microscopy to differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. Br J Dermatol 1998; 138:593.
  68. Domloge-Hultsch N, Anhalt GJ, Gammon WR, et al. Antiepiligrin cicatricial pemphigoid. A subepithelial bullous disorder. Arch Dermatol 1994; 130:1521.
  69. Chan LS, Fine JD, Briggaman RA, et al. Identification and partial characterization of a novel 105-kDalton lower lamina lucida autoantigen associated with a novel immune-mediated subepidermal blistering disease. J Invest Dermatol 1993; 101:262.
  70. Mascaró JM Jr, Zillikens D, Giudice GJ, et al. A subepidermal bullous eruption associated with IgG autoantibodies to a 200 kd dermal antigen: the first case report from the United States. J Am Acad Dermatol 2000; 42:309.
  71. Epstein JH, Tuffanelli DL, Epstein WL. Cutaneous changes in the porphyrias. A microscopic study. Arch Dermatol 1973; 107:689.
  72. Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita. Cochrane Database Syst Rev 2003; :CD004056.
  73. Intong LR, Murrell DF. Management of epidermolysis bullosa acquisita. Dermatol Clin 2011; 29:643.
  74. Gürcan HM, Ahmed AR. Current concepts in the treatment of epidermolysis bullosa acquisita. Expert Opin Pharmacother 2011; 12:1259.
  75. Cunningham BB, Kirchmann TT, Woodley D. Colchicine for epidermolysis bullosa acquisita. J Am Acad Dermatol 1996; 34:781.
  76. Megahed M, Scharffetter-Kochanek K. Epidermolysis bullosa acquisita--successful treatment with colchicine. Arch Dermatol Res 1994; 286:35.
  77. Hughes AP, Callen JP. Epidermolysis bullosa acquisita responsive to dapsone therapy. J Cutan Med Surg 2001; 5:397.
  78. Miyake H, Morishima Y, Komai R, et al. Epidermolysis bullosa acquisita: correlation of IgE levels with disease activity under successful betamethasone/dapsone combination therapy. Acta Derm Venereol 2001; 81:429.
  79. Sami N. Mycophenolate mofetil (MMF) in the treatment of epidermolysis bullosa acquisita (EBA) long-term follow-up. JAAD Case Rep 2015; 1:321.
  80. Caldwell JB, Yancey KB, Engler RJ, James WD. Epidermolysis bullosa acquisita: efficacy of high-dose intravenous immunoglobulins. J Am Acad Dermatol 1994; 31:827.
  81. Kofler H, Wambacher-Gasser B, Topar G, et al. Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita. J Am Acad Dermatol 1997; 36:331.
  82. Meier F, Sönnichsen K, Schaumburg-Lever G, et al. Epidermolysis bullosa acquisita: efficacy of high-dose intravenous immunoglobulins. J Am Acad Dermatol 1993; 29:334.
  83. Mohr C, Sunderkötter C, Hildebrand A, et al. Successful treatment of epidermolysis bullosa acquisita using intravenous immunoglobulins. Br J Dermatol 1995; 132:824.
  84. Sadler E, Schafleitner B, Lanschuetzer C, et al. Treatment-resistant classical epidermolysis bullosa acquisita responding to rituximab. Br J Dermatol 2007; 157:417.
  85. 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.
  86. Saha M, Cutler T, Bhogal B, et al. Refractory epidermolysis bullosa acquisita: successful treatment with rituximab. Clin Exp Dermatol 2009; 34:e979.
  87. Schmidt E, Benoit S, Bröcker EB, et al. Successful adjuvant treatment of recalcitrant epidermolysis bullosa acquisita with anti-CD20 antibody rituximab. Arch Dermatol 2006; 142:147.
  88. Niedermeier A, Eming R, Pfütze M, et al. Clinical response of severe mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption and rituximab (anti-CD20 monoclonal antibodies). Arch Dermatol 2007; 143:192.
  89. Oktem A, Akay BN, Boyvat A, et al. Long-term results of rituximab-intravenous immunoglobulin combination therapy in patients with epidermolysis bullosa acquisita resistant to conventional therapy. J Dermatolog Treat 2017; 28:50.
  90. Mercader P, Rodenas JM, Peña A, Mascaro JM Jr. Fatal Pseudomona pneumonia following rituximab therapy in a patient with epidermolysis bullosa acquisita. J Eur Acad Dermatol Venereol 2007; 21:1141.
  91. Egan CA, Brown M, White JD, Yancey KB. Treatment of epidermolysis bullosa acquisita with the humanized anti-Tac mAb daclizumab. Clin Immunol 2001; 101:146.
  92. Furue M, Iwata M, Yoon HI, 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.
  93. Miller JL, Stricklin GP, Fine JD, et al. Remission of severe epidermolysis bullosa acquisita induced by extracorporeal photochemotherapy. Br J Dermatol 1995; 133:467.
  94. Gordon KB, Chan LS, Woodley DT. Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy. Br J Dermatol 1997; 136:415.
  95. Lehman JS, Camilleri MJ, Gibson LE. Epidermolysis bullosa acquisita: concise review and practical considerations. Int J Dermatol 2009; 48:227.
  96. Kim JH, Kim YH, Kim SC. Epidermolysis bullosa acquisita: a retrospective clinical analysis of 30 cases. Acta Derm Venereol 2011; 91:307.
  97. Edwards S, Wakelin SH, Wojnarowska F, et al. Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis, and immunopathology in 11 children. Pediatr Dermatol 1998; 15:184.