Epidermolysis Bullosa Acquisita Clinical Presentation

  • Author: Lawrence S Chan, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Nov 15, 2011
 

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 the secondary scarring often causes restriction of mobility in the extensor skin surfaces.

In a subset of patients with generalized epidermolysis bullosa acquisita, the onset of disease is somewhat rapid, more wide spread, and inflammatory. 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 mucus 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, 26 international experts of mucous membrane pemphigoid had 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 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.

Epidermolysis bullosa acquisita has been reported to develop in a 73-year-old patient after a 2-week treatment of antibiotics.

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Physical

The skin and mucus membrane manifestations of epidermolysis bullosa acquisita (EBA) take several forms, as follows: a noninflammatory or mildly inflammatory disease affecting trauma-prone extensor skin surfaces, a generalized inflammatory disease, and a predominant mucus membrane disease.

The noninflammatory or mildly inflammatory form is the most common form of epidermolysis bullosa acquisita, manifested as tense vesicles and bullae, and erosions primarily on the extensor surfaces of hands, knuckles, elbows, knees, and ankles. The blisters may be hemorrhagic. Blisters on mucus membranes rupture easily; the most common manifestation is erosion. 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 it resembles 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.[6] The generalized inflammatory form usually heals with minimal scarring and milia formation.

A third variant of epidermolysis bullosa acquisita predominantly involves mucus membranes. This form of epidermolysis bullosa acquisita can affect mucous membranes of buccal, conjunctival, gingival, palatal, nasopharyngeal, rectal, genital, and esophageal mucosae. This variant clinically resembles mucous membrane pemphigoid and can result in significant mucosal scarring and dysfunction. A recent international consensus statement published in Archives of Dermatology (March 2002) has reassigned this group of patients to the category of mucous membrane pemphigoid.[7]

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.

An inflammatory variant of epidermolysis bullosa acquisita with autoantibodies to a central collagenous domain has been described. Three young patients with Japanese ethnic background were reported to have a generalized inflammatory blistering disease. These patients were readily responsive to systemic corticosteroids treatment, and the disease healed without scarring. The IgG autoantibodies from these 3 patients did not recognize the NC1 domain, but it did recognize the central triple-helical collagenous domain of type VII collagen. A patient with the inflammatory variant exhibited clinical morphology similar to that of toxic epidermal necrolysis and dermatitis herpetiformis.[8] A patient was reported to manifest with a localized form in periorbital areas.[9]

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Causes

Epidermolysis bullosa acquisita (EBA) is an autoimmune disease, manifested by IgG autoantibodies that target a major skin basement membrane component, collagen VII. Collagen VII is the major protein of anchoring fibrils and connects the epithelial basement membrane to the dermis. Autoantibodies specific for collagen VII alter the dermal-epidermal junctional adhesion and lead to dermal-epidermal separation. The initiating event that leads to autoantibody production is unknown. Recently, a subset of epidermolysis bullosa acquisita, which is milder clinically, has been identified to be mediated by IgA, rather than IgG autoantibodies. A small group of patients had autoantibodies to the collagenous domain, rather than the NC1 domain of collagen VII.[10]

Immunogenetic studies revealed that most black patients from the southeastern part of the United States had an association with human leukocyte antigen DR2 (HLA-DR2). Subsequent studies on a larger population of white patients failed to reveal any statistically significant HLA allele associations with epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita affecting several family members has been reported, supporting a genetic component.

Rarely, patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease, develop a generalized blistering skin disease with clinical and immunopathologic features of epidermolysis bullosa acquisita.

  • These patients have a subepidermal blistering skin disease characterized by IgG, IgA, and C3 deposition at the skin basement membrane zone.
  • Sera from these patients recognize the NC1 domain of type VII collagen, the same target antigen recognized by patients with epidermolysis bullosa acquisita.
  • The fact that epidermolysis bullosa acquisita, an organ-specific autoimmune disease, can develop in patients who already have a systemic autoimmune disease suggests that systemic autoimmunity can provoke an organ-specific autoimmune disease.
  • Alternatively, the nonspecific inflammatory process present in systemic lupus may induce the release and exposure of basement membrane antigens to autoreactive lymphocytes by a process termed epitope spreading, subsequently leading to autoimmunity against the epidermolysis bullosa acquisita antigen.[11]

Epidermolysis bullosa acquisita also is associated with Crohn disease, an inflammatory bowel disease characterized by T-cell infiltration in the small intestine. Type VII collagen is expressed in intestinal epithelial basement membranes.

  • The association of epidermolysis bullosa acquisita and inflammatory bowel disease may have an immunologic basis.
  • It has been observed that a significant number of patients with Crohn disease have circulating IgG autoantibodies that recognize the NC1 domain as demonstrated by enzyme-linked immunosorbent assay (ELISA), although they do not have epidermolysis bullosa acquisita clinically.
  • The presence of these autoantibodies may represent a preclinical epidermolysis bullosa acquisita phenomenon, induced by the release and exposure of intestinal type VII collagen to autoreactive lymphocytes because of epitope spreading caused by the inflammatory reaction in their gut.

An initial experiment of passively transferring IgG autoantibodies from human patients with epidermolysis bullosa acquisita to mice does not induce clinical disease in mouse skin.

  • The failure of passive transfer experiments to induce disease may be due to several possible reasons.
  • Subsequently, however, rabbit antibodies raised against human recombinant protein type VII collagen were able to induce blisters in mice, as did rabbit antibodies raised against mouse type VII collagen.[12, 13]
  • Lately, affinity-purified antitype VII collagen autoantibodies from epidermolysis bullosa acquisita patients have been shown to induce blisters in an adult hairless mouse strain (SKH1), further supporting a pathogenic role of these autoantibodies.[14]
  • The binding of pathogenic IgG to type VII collagen may be a necessary but insufficient step for blister formation.
  • Additional steps required for blister formation, such as recruitment and release of inflammatory mediators, may not occur in this model.
  • The binding of human anti–type VII collagen autoantibodies may not recognize critical sites on mouse type VII collagen, thus rendering these autoantibodies incapable of inducing blister formation.
  • The turnover of existing anchoring fibrils may be very slow such that epidermolysis bullosa acquisita develops only after autoantibodies inhibit new anchoring fibril formation over a prolonged period. This would not be similar to short-term neonatal mouse studies.

In some patients with epidermolysis bullosa acquisita and bullous systemic lupus erythematosus, circulating autoantibodies against other skin basement membrane components, such as bullous pemphigoid antigens, laminin-5, and laminin-6, in addition to type VII collagen, have been reported. These observations further support the role of epitope spreading.[7, 15, 16]

An active experimental animal model of epidermolysis bullosa acquisita would facilitate the understanding of the disease pathogenesis; however, it is currently unavailable.

New findings were recently reported that autoantibodies from patients affected with epidermolysis bullosa acquisita recognized not only the NC1 domain but also the NC2 domain of type VII collagen. Furthermore, the NC2 domain mediates antiparallel dimer formation in experimental conditions. Therefore, the targeting of the NC2 domain by epidermolysis bullosa acquisita autoantibodies may destabilize anchoring fibrils by interfering with antiparallel dimer formation, leading to dermal-epidermal disadherence.

Rabbit antimouse type VII collagen antibodies induced subepidermal blisters in mice, identically as occurs in human patients with epidermolysis bullosa acquisita, supporting the role of antitype VII collagen autoantibodies in the pathogenesis of epidermolysis bullosa acquisita. Rabbit antimouse type VII collagen antibodies were not able to induce blisters in C5-deficient mice, pointing to a role for complement activation in the pathogenesis of epidermolysis bullosa acquisita.

Immunization of type VII collagen in athymic nude SJL mice did not induce an autoimmune response, whereas the repletion of T cells from type VII collagen–immunized wild type mice to the athymic mice showed autoantibody production and resulted in a blistering disease phenotype, supporting the role of T cells in the induction of epidermolysis bullosa acquisita.[17]

The fact that epidermolysis bullosa acquisita is responsive to rituximab antibody to CD20 supports the role of B cells.[18, 19]

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Contributor Information and Disclosures
Author

Lawrence S Chan, MD  Dr Orville J Stone Professor of Dermatology, Head, Department of Dermatology, University of Illinois College of Medicine

Lawrence S Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Dermatological Association, American Medical Association, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois State Medical Society, Microcirculatory Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

David Woodley, MD  Co-Chair, Professor, Department of Medicine, Division of Dermatology, University of Southern California

David Woodley, MD is a member of the following medical societies: American Academy of Dermatology, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Physicians, American Federation for Medical Research, American Society for Clinical Investigation, New York Academy of Medicine, Society for Investigative Dermatology, and Southern Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Ponciano D Cruz Jr, MD  Vice-Chair, JB Shelmire Professor, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: RCTS Consulting fee Independent contractor; Mary Kay Cosmetics Honoraria Consulting; Galderma Grant/research funds Principal Investigator

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Edward F Chan, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Olivry T, Fine J, Dunston SM, et al. Canine epidermolysis bullosa acquisita: Circulating autoantibodies target the aminoterminal noncollagenous (NC1) domain of collagen VII in anchoring fibrils. Vet Dermatol. 1998;9:19-32.

  2. Xu L, Chen M, Peng J, O'Toole EA, Woodley DT, Chan LS. Molecular cloning and characterization of a cDNA encoding canine type VII collagen non-collagenous (NC1) domain, the target antigen of autoimmune disease epidermolysis bullosa acquisita (EBA). Biochim Biophys Acta. Oct 22 1998;1408(1):25-34. [Medline].

  3. Bernard P, Prost C, Aucouturier P, Durepaire N, Denis F, Bonnetblanc JM. The subclass distribution of IgG autoantibodies in cicatricial pemphigoid and epidermolysis bullosa acquisita. J Invest Dermatol. Aug 1991;97(2):259-63. [Medline].

  4. Gandhi K, Chen M, Aasi S, Lapiere JC, Woodley DT, Chan LS. Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype. J Clin Immunol. Nov 2000;20(6):416-23. [Medline].

  5. Zumelzu C, Le Roux-Villet C, Loiseau P, et al. Black Patients of African Descent and HLA-DRB1*15:03 Frequency Overrepresented in Epidermolysis Bullosa Acquisita. J Invest Dermatol. Dec 2011;131(12):2386-93. [Medline].

  6. 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. Feb 1996;134(2):336-9. [Medline].

  7. Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol. Mar 2002;138(3):370-9. [Medline].

  8. Madan V, Jamieson LA, Bhogal BS, Wong CS. Inflammatory epidermolysis bullosa acquisita mimicking toxic epidermal necrolysis and dermatitis herpetiformis. Clin Exp Dermatol. Dec 2009;34(8):e705-8. [Medline].

  9. Derrow AE, Mutasim DF. Periorbital papulovesicular eruption in an elderly man. Localized periorbital epidermolysis bullosa acquisita (EBA). Arch Dermatol. May 2009;145(5):589-94. [Medline].

  10. Vodegel RM, de Jong MC, Pas HH, Jonkman MF. IgA-mediated epidermolysis bullosa acquisita: two cases and review of the literature. J Am Acad Dermatol. Dec 2002;47(6):919-25. [Medline].

  11. Chan LS, Vanderlugt CJ, Hashimoto T, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. Feb 1998;110(2):103-9. [Medline].

  12. 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. Apr 2005;115(4):870-8. [Medline].

  13. 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. Jun 2006;126(6):1323-30. [Medline].

  14. Chen L, Peterson JD, Zheng WY, Lin SX, Chan LS. Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells. Clin Exp Immunol. Aug 2006;145(2):322-31. [Medline].

  15. Chen M, Marinkovich MP, Jones JC, O'Toole EA, Li YY, Woodley DT. 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. Feb 1999;112(2):177-83. [Medline].

  16. Jonkman MF, Schuur J, Dijk F, et al. Inflammatory variant of epidermolysis bullosa acquisita with IgG autoantibodies against type VII collagen and laminin alpha3. Arch Dermatol. Feb 2000;136(2):227-31. [Medline].

  17. Muller R, Dahler C, Mobs C, et al. T and B cells target identical regions of the non-collagenous domain 1 of type VII collagen in epidermolysis bullosa acquisita. Clin Immunol. Jan/2010;EPub:[Medline].

  18. Peterson JD, Chan LS. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the initial use to 2007. Ther Clin Risk Manag. Feb/2009;5:1-7. [Medline].

  19. Saha M, Cutler T, Bhogal B, Black MM, Groves RW. Refractory epidermolysis bullosa acquisita: successful treatment with rituximab. Clin Exp Dermatol. Dec/2009;34:e979-80. [Medline].

  20. 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. Sep 1993;101(3):262-7. [Medline].

  21. Gammon WR, Briggaman RA, Inman AO 3rd, 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. Feb 1984;82(2):139-44. [Medline].

  22. 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. Jan 1997;108(1):68-72. [Medline].

  23. 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. Jan 2007;156(1):194-6. [Medline].

  24. 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. Feb 2007;143(2):192-8. [Medline].

  25. Sadler E, Schafleitner B, Lanschuetzer C, et al. Treatment-resistant classical epidermolysis bullosa acquisita responding to rituximab. Br J Dermatol. Aug 2007;157(2):417-9. [Medline].

  26. 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. Feb 2006;142(2):147-50. [Medline].

  27. Wallet-Faber N, Franck N, Batteux F, et al. Epidermolysis bullosa acquisita following bullous pemphigoid, successfully treated with the anti-CD20 monoclonal antibody rituximab. Dermatology. 2007;215(3):252-5. [Medline].

  28. Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern Med. Aug 1982;97(2):165-70. [Medline].

  29. American College of Rheumatology. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum. Nov 1996;39(11):1791-801. [Medline].

  30. Chan LS. Epidermolysis Bullosa Acquisita. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 2nd ed. St. Louis, Mo: Mosby; 2005:191-3.

  31. Chan LS, Chen M, Woodley DT. Epidermolysis bullosa acquisita in the elderly: Clinical manifestations, diagnosis and therapy. J Geriat Dermatol. 1996;4:47-52.

  32. Chan LS, Lapiere JC, Chen M, et al. Bullous systemic lupus erythematosus with autoantibodies recognizing multiple skin basement membrane components, bullous pemphigoid antigen 1, laminin-5, laminin-6, and type VII collagen. Arch Dermatol. May 1999;135(5):569-73. [Medline].

  33. Chen M, Keene DR, Costa FK, Tahk SH, Woodley DT. 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. Jun 15 2001;276(24):21649-55. [Medline].

  34. 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. Jun 6 1997;272(23):14516-22. [Medline].

  35. Chen M, Woodley DT. The cartilage matrix protein NC1 submodule of type VII collagen binds to fibronectin and constitutes a major new antigenic epitope for EBA autoantibodies. J Invest Dermatol. 1999;112:536.

  36. Delbaldo C, Chen M, Friedli A, et al. Drug-induced epidermolysis bullosa acquisita with antibodies to type VII collagen. J Am Acad Dermatol. May 2002;46(5 Suppl):S161-4. [Medline].

  37. Domloge-Hultsch N, Gammon WR, Briggaman RA, Gil SG, Carter WG, Yancey KB. Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease. J Clin Invest. Oct 1992;90(4):1628-33. [Medline].

  38. 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. Jun 1985;84(6):472-6. [Medline].

  39. 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. May 2009;160(5):1090-3. [Medline].

  40. Jones DA, Hunt SW 3rd, Prisayanh PS, Briggaman RA, Gammon WR. 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. Feb 1995;104(2):231-5. [Medline].

  41. Keene DR, Sakai LY, Lunstrum GP, Morris NP, Burgeson RE. Type VII collagen forms an extended network of anchoring fibrils. J Cell Biol. Mar 1987;104(3):611-21. [Medline].

  42. Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa acquisita: a systematic literature review. Arch Dermatol. Mar 2002;138(3):380-4. [Medline].

  43. Lapiere JC, Chan LS, Woodley DT. Epidermolysis bullosa acquisita. In: Arndt KA, Robinson JK, Leboit PE, Wintroub BU, eds. Cutaneous Medicine and Surgery: An Integrated Program in Dermatology. Philadelphia, Pa: WB Saunders; 1996:685-90.

  44. 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. Oct 1993;92(4):1831-9. [Medline].

  45. Luke MC, Darling TN, Hsu R, et al. Mucosal morbidity in patients with epidermolysis bullosa acquisita. Arch Dermatol. Aug 1999;135(8):954-9. [Medline].

  46. McCuaig CC, Chan LS, Woodley DT, Rasmussen JE, Cooper KD. Epidermolysis bullosa acquisita in childhood. Differentiation from hereditary epidermolysis bullosa. Arch Dermatol. Jul 1989;125(7):944-9. [Medline].

  47. Noe MH, Chen M, Woodley DT, Faieley JA. Familial epidermolysis bullosa acquisita. Dermatol Online. Dec/2008;14:2. [Medline].

  48. Parente MG, Chung LC, Ryynanen J, et al. Human type VII collagen: cDNA cloning and chromosomal mapping of the gene. Proc Natl Acad Sci U S A. Aug 15 1991;88(16):6931-5. [Medline].

  49. Roenigk HH Jr, Ryan JG, Bergfeld WF. Epidermolysis bullosa acquisita. Report of three cases and review of all published cases. Arch Dermatol. Jan 1971;103(1):1-10. [Medline].

  50. Sakai LY, Keene DR, Morris NP, Burgeson RE. Type VII collagen is a major structural component of anchoring fibrils. J Cell Biol. Oct 1986;103(4):1577-86. [Medline].

  51. Sitaru AG, Sesarman A, Mihai S, et al. T cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita. J Immunol. Feb 1 2010;184(3):1596-603. [Medline].

  52. 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. Dec 1997;77(6):623-32. [Medline].

  53. 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. Apr 19 1984;310(16):1007-13. [Medline].

  54. Woodley DT, Chang C, Saadat P, Ram R, Liu Z, Chen M. 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. May 2005;124(5):958-64. [Medline].

  55. Woodley DT, Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz S, eds. Fitzpatrick's Dermatology in General Medicine. New York, NY: McGraw-Hill; 1999:702-9.

  56. Yaoita H, Briggaman RA, Lawley TJ, Provost TT, Katz SI. Epidermolysis bullosa acquisita: ultrastructural and immunological studies. J Invest Dermatol. Apr 1981;76(4):288-92. [Medline].

 
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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.
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.
 
 
 
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