Bullous pemphigoid

Last Updated: 2021-10-18

Author(s): Anzengruber F., Navarini A.

ICD11: EB41.0

Lever 1953

Dermatitis herpetiformis senilis, parapemphigus, senile pemphigus

  • Autoimmune disease in which autoantibodies attack hemidesmosomal structural proteins of the basement membrane zone, eventually leading to blister formation.
  • Special forms:
    • Bullous localised pemphigoid
    • Bullous vegetating pemphigoid
    • Scarring pemphigoid
    • Pemphigoid gestationis
    • IgA-linear dermatosis

  • Incidence: approx. 13 cases/1'000'000/year
  • Incidence (>80 y.): 190/1,000,000/ year
  • Men : women = 2 : 1
  • Associations
    • Dementia
    • Morbus Parkinson
    • Epilepsy
    • Multiple sclerosis

  • Molecular pathogenesis:
    • In bullous pemphigoid, 2 IgG autoantibodies, anti-BP-180 and anti-BP-230, attack hemidesmosomal proteins. Antibodies also attack the NC16A epitope of the BP 180 protein. This leads to the formation of antigen-antibody complexes and eventually to complement activation. This molecular damage leads to subepidermal blistering.
  • Associations / triggers:
    • 1/3 of all patients suffer from neurological and/or psychiatric diseases
      • Dementia
      • M. Parkinson's
      • Stroke
      • Epilepsy
      • Multiple sclerosis
    • Hematological diseases
    • Oncological diseases
    • Genetics
      • Haplotype HLA-DQB1*0301
  • Drug as possible trigger:
    • Antibiotics
      • Amoxicillin
      • Ampicillin
      • Cephalexin
      • penicillamine
      • Penicillin V
      • Sulfonamides and derivatives
    • Antihypertensives
      • ACE inhibitors
        • Captopril
      • Enalapril
      • Furosemide
      • Hydroxychloroquine
    • TNF antagonists
    • Cytostatic agents
      • Locally applied 5-fluorouracil
    • Antiparkinsonian drugs
      • Levodopa
    • Analgesics
      • NSAIDs
    • Aminosalicylates
      • Sulphonamides
        • Sulfasalazine
        • Salazosulfapyridine
    • Antifungals
      • Terbinafine
  • Light
    • UVA rays
    • UVB rays
    • Photodynamic therapy
  • Neoplasia

  • Blisters (and erosions), sometimes urticaria
  • In some cases, a premonitory stage may precede, in which the patient complains of severe itching but no blisters are visible
  • Mucosal involvement is seen in up to 30% (always inspect mucosa!)
  • Nikolski phenomenon I: lateral spatula pressure causes bullae to develop: negative
  • Nikolski phenomenon II: Bullae can be displaced by lateral spatula pressure: positive

  • Anamnesis
    • Itching?
    • Intake of spironolactone, phenothiazines (e.g. furosemide)?
    • Associated underlying diseases?
  • Clinic
    • Always inspect mucosa!
    • Nikolski sign
  • Biopsy
    • Dermatopathology (it is recommended that a small intact blister be completely removed by biopsy.)
    • Direct immunofluorescence

  • Dermopathological examination alone is not diagnostic
  • Subepidermal cleft formation, lymphocytic inflammatory infiltrate, eosinophilic granulocytes
  • Direct immunofluroescence has very high sensitivity (90%)

None possible.

  • Chronic-recurrent course, disease typically in remission after 2-5 years
  • 1-year mortality: 30%

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  2. Darling TN, McGrath JA, Yee C, et al. Premature Termination Codons Are Present on Both Alleles of the Bullous Pemphigoid Antigen 2/Type XVII Collagen Gene in Five Austrian Families with Generalized Atrophic Benign Epidermolysis Bullosa. Journal of Investigative Dermatology 1997;108:463-8.
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