Skip to main content

Advertisement

SpringerLink
Log in

Autoimmunity to Type VII Collagen: Epidermolysis Bullosa Acquisita

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune, mechanobullous disease with clinical features reminiscent of genetic dystrophic epidermolysis bullosa (DEB). EBA patients have skin fragility, blisters, scars, and milia formation. DEB is due to a genetic defect in the gene-encoding type VII collagen, which makes anchoring fibrils, structures that attach the epidermis and its underlying basement membrane zone onto the papillary dermis. DEB patients have a decrease in normally functioning anchoring fibrils. EBA patients have the same problem, but their decrease in normally functioning anchoring fibrils is because of an abnormality in their immune system in which they produce anti-type VII collagen antibodies that attack their anchoring fibrils. These IgG anti-type VII collagen antibodies are “pathogenic” because when injected into a mouse, the mouse develops an EBA-like blistering disease. EBA has several distinct clinical presentations. It can present with features similar to DEB. It can also present with features reminiscent of bullous pemphigoid, cicatricial pemphigoid, Brunsting–Perry pemphigoid, or IgA bullous dermatosis. Treatment for EBA is unsatisfactory. Some therapeutic success has been reported with colchichine, dapsone, photopheresis, infliximab, and IVIG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Woodley DT et al (1984) Identification of the skin basement membrane autoantigen in epidermolysis bullosa acquisita. N Engl J Med 310:1007

    Article  PubMed  CAS  Google Scholar 

  2. Woodley DT et al (1988) The epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen. J Clin Invest 81:683

    PubMed  CAS  Google Scholar 

  3. Woodley DT, Ram R, Doostan A, Bandyopadhyay P, Huang Y, Remington J, Hou YP, Keene DR, Liu Z, Chen M (2006) Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients. J Invest Dermatol 126:1324–1330

    Article  CAS  Google Scholar 

  4. Roenigk HH et al (1971) Epidermolysis bullosa acquisita: report of three cases and review of all published cases. Arch Dermatol 103:10

    Google Scholar 

  5. Kushniruk W (1973) The immunopathology of epidermolysis bullosa acquisita. Can Med Assoc J 108:1143

    PubMed  CAS  Google Scholar 

  6. Gammon WR et al (1988) Increased frequency of HLA DR2 in patients with autoantibodies to EBA antigen: evidence that the expression of autoimmunity to type VII collagen is HLA class II allele associated. J Invest Dermatol 91:228

    Article  PubMed  CAS  Google Scholar 

  7. Gibbs RB, Minus HR (1975) Epidermolysis bullosa acquisita with electron microscopical studies. Arch Dermatol 111:215

    Article  PubMed  CAS  Google Scholar 

  8. Nieboer C et al (1980) Epidermolysis bullosa acquisita: immunofluorescence, electron microscopic and immunoelectron microscopic studies in four patients. Br J Dermatol 102:383

    Article  PubMed  CAS  Google Scholar 

  9. Yaoita H et al (1981) Epidermolysis bullosa acquisita: ultrastructural and immunological studies. J Invest Dermatol 76:288

    Article  PubMed  CAS  Google Scholar 

  10. Briggaman RA, Wheeler CE Jr (1975) The epidermal–dermal junction. J Invest Dermatol 65:71

    Article  PubMed  CAS  Google Scholar 

  11. Keene DR et al (1987) Type VII collagen forms an extended network of anchoring fibrils. J Cell Biol 104:611

    Article  PubMed  CAS  Google Scholar 

  12. Ray TL et al (1982) Epidermolysis bullosa acquisita and inflammatory bowel disease. J Am Acad Dermatol 6:242

    PubMed  CAS  Google Scholar 

  13. Dahl MGC (1979) Epidermolysis bullosa acquisita: a sign of cicatricial pemphigoid? Br J Dermatol 101:475

    Article  PubMed  CAS  Google Scholar 

  14. Bruckner-Tuderman L, Nilssen O, Zimmermann DR, Dours-Zimmermann MT, Kalinke DU, Gedde-Dahl T Jr, Winberg JO (1995) Immunohistochemical and mutation analyzes demonstrate that procollagen VII is processed to collagen VII through removal of the NC-2 domain. J Cell Biol 131:551–559

    Article  PubMed  CAS  Google Scholar 

  15. Christiano AM, Greenspan DS, Lee S, Uitto J (1994) Cloning of human type VII collagen: complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms. J Biol Chem 269:20256–20262

    PubMed  CAS  Google Scholar 

  16. Chen M et al (1997) Interactions of the amino-terminal noncollagenous (NC1) domain of type VII collagen with extracellular matrix components. J Biol Chem 272:14516

    Article  PubMed  CAS  Google Scholar 

  17. Bauer EA, Eisen AZ (1978) Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture. J Exp Med 148:1378

    Article  PubMed  CAS  Google Scholar 

  18. Lapiere J-C et al (1993) Epitope mapping of type VII collagen: identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa. J Clin Invest 92:1831

    Article  PubMed  CAS  Google Scholar 

  19. Jones DA et al (1995) Immunodominant autoepitopes of type VII collagen are short, paired peptide sequences within the fibronectin type III homology region of the non-collagenous (NC1) domain. J Invest Dermatol 104:231

    Article  PubMed  CAS  Google Scholar 

  20. Woodley DT et al (1987) Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen. J Clin Invest 179:1826

    Google Scholar 

  21. Park SB, Cho KH, Youn JL, Hwang DH, Kim SC, Chung JH (1997) Epidermolysis bullosa acquisita in childhood—a case mimicking chronic bullous dermatosis of childhood. Clin Exp Dermatol 22:220–222

    Article  PubMed  CAS  Google Scholar 

  22. Callot-Mellot C, Bodemer C, Caux F, Bourgault-Villada I, Fraitag S, Goudie G, Heller M, de Prost Y, Prost C (1997) Epidermolysis bullosa acquisita in childhood. Arch Dermatol 133:1122–1126

    Article  PubMed  CAS  Google Scholar 

  23. Lapiere J-C et al (1994) Type VII collagen specifically binds fibronectin via a unique subdomain within the collagenous triple helix. J Invest Dermatol 103:637

    Article  PubMed  CAS  Google Scholar 

  24. Chen M, Keene DR, Costa FK, Tahk SH, Woodley DT (2001) 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 276:21649–21655

    PubMed  CAS  Google Scholar 

  25. Gammon WR et al (1984) Epidermolysis bullosa acquisita: a pemphigoid-like disease. J Am Acad Dermatol 11:820

    PubMed  CAS  Google Scholar 

  26. Woodley DT, Chang C, Saadat P, Ram R, Liu Z, Chen M (2005) 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 124:958–964

    Article  PubMed  CAS  Google Scholar 

  27. Sitaru C, Mihai S, Otto C, Chiriac MT, Hausser I, Dotterweich B, Saito H, Rose C, Ishiko A, Zillikens D (2005) Induction of dermal–epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. J Clin Invest 115:870–878

    Article  PubMed  CAS  Google Scholar 

  28. Stewart MI, Woodley DT (1991) Acquired epidermolysis bullosa and associated symptomatic esophageal webs. Arch Dermatol 127:373

    Article  PubMed  CAS  Google Scholar 

  29. Kurzhals G et al (1991) Acquired epidermolysis bullosa with the clinical features of Brunsting–Perry cicatricial bullous pemphigoid. Arch Dermatol 127:391

    Article  PubMed  CAS  Google Scholar 

  30. Hashimoto T, Ishiko A, Shimizu H, Tanaka T, Dodd HJ, Bhogal BS, Black MM, Nishikawa T (1996) A case of linear IgA bullous dermatosis with IgA anti-type VII collagen autoantibodies. Br J Dermatol 134:336–339

    Article  PubMed  CAS  Google Scholar 

  31. Rusenko KW, Gammon WR, Briggaman RA (1989) Type VII collagen is the antigen recognized by IgA anti-sub lamina densa autoantibodies. J Invest Dermatol 92:510, Abstract

    Article  Google Scholar 

  32. Bauer JW, Schaeppi H, Metze D, Muss W, Pohla-Gubo G, Hametner R, Ruckhofer J, Grabner G, Hintner H (1999) Ocular involvement in IgA-epidermolysis bullosa acquisita. Br J Dermatol 141:887–892

    Article  PubMed  CAS  Google Scholar 

  33. Lee CW (2000) Serum IgA autoantibodies in patients with epidermolysis bullosa acquisita: a high frequency of detection. Dermatology 200:83–84

    Article  PubMed  CAS  Google Scholar 

  34. Edwards S, Wakelin SH, Wojnarowska F, Marsden RA, Kirtschig G, Bhogal B, Black MM (1998) Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis and immunopathology in 11 children. Pediatr Dermatol 15:184–190

    Article  PubMed  CAS  Google Scholar 

  35. Burke WA et al (1986) Epidermolysis bullosa acquisita in a patient with multiple endocrinopathies syndrome. Arch Dermatol 122:187

    Article  PubMed  CAS  Google Scholar 

  36. Chan L, Woodley DT (1996) Pemphigoid: bullous and cicatricial. In: Lichtenstein LM, Fauci AS (eds) Current therapy in allergy, immunology and rheumatology, 5th edn. Mosby, St. Louis, p 93

    Google Scholar 

  37. Lever WF, Schaumburg-Lever G (1990) Congenital diseases (genodermatoses). In: Lever WF, Schaumburg-Lever G (eds) Histopathology of the skin. Lippincott, Philadelphia, p 78

    Google Scholar 

  38. Richter BJ, McNutt NS (1979) The spectrum of epidermolysis bullosa acquisita. Arch Dermatol 115:1325

    Article  PubMed  CAS  Google Scholar 

  39. Woodley DT et al (1983) Localization of basement membrane components after dermal–epidermal junction separation. J Invest Dermatol 81:149

    Article  PubMed  CAS  Google Scholar 

  40. Gammon WR et al (1990) Direct immunofluorescence studies of sodium chloride—separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J Am Acad Dermatol 22:664

    PubMed  CAS  Google Scholar 

  41. Domloge-Hultsch N, Anhalt GJ, Gammon WR, Lazarova Z, Briggaman R, Welch M, Jabs DA, Huff C, Yancey KB (1994) Antiepiligrin cicatricial pemphigoid: a subepithelial bullous disorder. Arch Dermatol 130:1521–1529

    Article  PubMed  CAS  Google Scholar 

  42. Ceilley E et al (1993) Labeling of fractured human skin with antibodies to BM 600/nicein, epiligrin, kalinin and other matrix components. J Dermatol Sci 5:97

    Article  PubMed  CAS  Google Scholar 

  43. Ghohestani RF, Hudson BG, Claudy A, Uitto J (2000) The α5 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 275:16002–16006

    Article  PubMed  CAS  Google Scholar 

  44. Zillikens D et al (2000) Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen. Br J Dermatol 143:1043

    Article  PubMed  CAS  Google Scholar 

  45. Chen M et al (1997) Development of an ELISA for rapid detection of anti-type VII collagen autoantibodies in epidermolysis bullosa acquisita. J Invest Dermatol 108:68

    Article  PubMed  CAS  Google Scholar 

  46. Cunningham BB et al (1996) Colchicine for epidermolysis bullosa (EBA). J Am Acad Dermatol 34:781

    Article  PubMed  CAS  Google Scholar 

  47. Mekori YA et al (1989) Inhibition of delayed hypersensitivity reaction by colchicine: colchicine inhibits interferon-gamma-induced expression of HLA-DR on a epithelial cell line. Clin Exp Immunol 78:230

    PubMed  CAS  Google Scholar 

  48. Crow LL et al (1988) Clearing of epidermolysis bullosa acquisita on cyclosporin A. J Am Acad Dermatol 19:937

    PubMed  CAS  Google Scholar 

  49. Connolly SM, Sander HM (1987) Treatment of epidermolysis bullosa acquisita with cyclosporin. J Am Acad Dermatol 16:890

    PubMed  CAS  Google Scholar 

  50. Rook AH et al (1990) Extracorporeal photochemotherapy for drug-resistant pemphigus vulgaris. Ann Intern Med 112:303

    PubMed  CAS  Google Scholar 

  51. Miller JL et al (1995) Remission of severe epidermolysis bullosa acquisita induced by extracorporeal photochemotherapy. Br J Dermatol 133:467

    Article  PubMed  CAS  Google Scholar 

  52. Gordon K et al (1997) Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy. Br J Dermatol 136:415

    Article  PubMed  CAS  Google Scholar 

  53. Bystryn J-C, Jiao D, Natow S (2002) Treatment of pemphigus with intravenous immunoglobulin. J Am Acad Dermatol 47:358–363

    Article  PubMed  Google Scholar 

  54. Meier F et al (1993) Epidermolysis bullosa acquisita: efficacy of high dose intravenous immunoglobulins. J Am Acad Dermatol 29:334

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, The Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    David T. Woodley, Jennifer Remington & Mei Chen

Authors
  1. David T. Woodley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer Remington
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David T. Woodley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woodley, D.T., Remington, J. & Chen, M. Autoimmunity to Type VII Collagen: Epidermolysis Bullosa Acquisita. Clinic Rev Allerg Immunol 33, 78–84 (2007). https://doi.org/10.1007/s12016-007-0027-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-007-0027-6

Keywords

Search

Navigation