Epidermolysis Bullosa Acquisita

Chronic Autoimmune Blistering Disease

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Presence of chronic blistering, erosive and/or crusting skin disease
  • More common diseases ruled out

Laboratory Testing

  • Initial serum testing – test for either pemphiguspemphigoid, and endomysial antibodies or epithelial skin antibodies
    • Broad screening recommended unless a specific immunobullous skin disease type is suspected
    • Serologic diagnosis – positive in 90% of cases
  • Pemphigoid panel
    • IgG basement membrane zone (BMZ) antibodies positive titer >1:10 with dermal pattern is diagnostic for epidermolysis bullosa acquisita (EBA)
    • Collagen type VII antibody IgG by enzyme-linked immunosorbent assay (ELISA) – order if IgG BMZ is diagnostic for EBA

Histology

  • Immunohistology
    • Perilesional skin biopsy for direct immunofluorescence (DIF) – gold standard for diagnosis
      • Linear BMZ deposition of IgG and/or third component of complement (C3) along BMZ of perilesional tissue
    • Dermal pattern localization of serum IgG BMZ antibodies on human split skin substrate by indirect immunofluorescence
      • Characteristically found in EBA
      • Also found in
      • Collagen VII IgG antibodies not increased
        • Up to one-third of laminin 332 antibody pemphigoid cases with dermal pattern BMZ antibody staining have underlying malignancy or will be diagnosed with malignancy within a few months
        • Further clinical evaluation should be pursued as indicated
      • Collagen VII antibodies increased
        • Unknown whether patients also may have laminin 332 antibodies
        • Association with malignancy and dermal pattern BMZ antibody staining should be considered

Differential Diagnosis

  • Collagen type VII IgG antibody and epithelial skin antibody

OR

  • Collagen type VII IgG antibody and IgG basement membrane zone (BMZ) antibodies

Epidermolysis bullosa acquisita (EBA) is a rare, chronic autoimmune blistering disease.

Epidemiology

  • Incidence – 25/100,000
  • Age
    • Peak onset in 40s for acquired form
    • Infancy for inherited form
  • Sex – M:F, equal
  • Genetics – mutation present in inherited forms
    • Multiple mutations may be responsible, including KRT5, KRT14, LAM3, LAMA3, LAMB3, LAMC2, COL17A2, ITGA3, ITGA6, ITGB4
    • Autosomal recessive inheritance

Pathophysiology

  • Subepidermal blister formation characterized by autoantibodies to structural components of skin and adjacent mucous membranes (specifically collagen VII)
  • Collagen VII – component of anchoring fibrils within epithelial basement membrane zone (BMZ) (skin and mucous membranes)
    • Patients with EBA characteristically develop IgG antibodies to collagen VII
    • Major epitopes for EBA antibody reactivity reside in noncollagenous amino-terminal domain (NC1)
    • Minor epitopes reside in noncollagenous carboxy-terminal domain (NC2) of the 3 identical alpha chains that comprise collagen VII

Clinical Presentation

  • Acquired EBA – 4 forms
    • Classical variant
      • Mechanobullous – slight trauma elicits blistering and erosions, typically on extensor surfaces of elbows, knees, hands, and feet
      • Noninflammatory
      • Healing of lesions results in atrophy, milia, scars, and pigmentation
    • Inflammatory variant
      • Resembles pemphigoid
      • Tense blistering on urticarial base
    • Cicatricial pemphigoidlike variant
      • Mucous membranes affected
      • Blistering lesions that scar
    • Brunsting-Perry pemphigoidlike variant
      • Head and neck involvement
      • Minimal mucosal disease
      • Blistering lesions that scar
  • Inherited EBA – 4 forms
    • Epidermolysis bullosa (EB) simplex
    • Dystrophic EB
    • Kindler syndrome
    • Junctional EB
      • Herlitz
      • Non-Herlitz – generalized
      • Non-Herlitz – localized
      • With pyloric atresia
      • Inversa
      • Late onset
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Cutaneous Direct Immunofluorescence, Biopsy 0092572
Method: Direct Immunofluorescence

Limitations 

Tissue must be submitted in Michel’s or Zeus medium; test cannot be performed on formalin-fixed tissue

Pemphigoid Antibody Panel - Epithelial Basement Membrane Zone Antibodies, IgG and IgA, BP180 and BP230 Antibodies, IgG 0092001
Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

Collagen Type VII Antibody IgG by ELISA 2010905
Method: Enzyme-Linked Immunosorbent Assay

Pemphigus Antibody Panel - Epithelial Cell Surface Antibodies and Desmoglein 1 and Desmoglein 3 Antibodies, IgG 0090650
Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

Tissue Transglutaminase (tTG) Antibody, IgA with Reflex to Endomysial Antibody, IgA by IFA 0050734
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Epithelial Skin Antibody 0090299
Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

Epithelial Basement Membrane Zone Antibody IgG 0092056
Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

General References

Baum S, Sakka N, Artsi O, Trau H, Barzilai A. Diagnosis and classification of autoimmune blistering diseases. Autoimmun Rev. 2014; 13(4-5): 482-9. PubMed

Gupta R, Woodley DT, Chen M. Epidermolysis bullosa acquisita. Clin Dermatol. 2012; 30(1): 60-9. PubMed

Intong LR, Murrell DF. Management of epidermolysis bullosa acquisita. Dermatol Clin. 2011; 29(4): 643-7. PubMed

Ishii N, Hamada T, Dainichi T, Karashima T, Nakama T, Yasumoto S, Zillikens D, Hashimoto T. Epidermolysis bullosa acquisita: what's new? J Dermatol. 2010; 37(3): 220-30. PubMed

Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: Clinical manifestations. J Dtsch Dermatol Ges. 2011; 9(10): 844-56; quiz 857. PubMed

Lara-Corrales I, Pope E. Autoimmune blistering diseases in children. Semin Cutan Med Surg. 2010; 29(2): 85-91. PubMed

Lehman JS, Camilleri MJ, Gibson LE. Epidermolysis bullosa acquisita: concise review and practical considerations. Int J Dermatol. 2009; 48(3): 227-35; quiz 235-6. PubMed

Parker SR, MacKelfresh J. Autoimmune blistering diseases in the elderly. Clin Dermatol. 2011; 29(1): 69-79. PubMed

Schmidt E, Zillikens D. The diagnosis and treatment of autoimmune blistering skin diseases. Dtsch Arztebl Int. 2011; 108(23): 399-405, I-III. PubMed

Medical Reviewers

Last Update: September 2017