Bullous pemphigoid

Last Updated: 2021-10-18

Author(s): Anzengruber, Navarini

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%

Topical therapy

  • Open blisters if necessary 
  • Topical steroids class III / IV, once daily
  • Antiseptics
    • Iodine-povidone wound ointment, solution, ointment gauze
    • Triclosan skin wash lotion
    • Polihexanide

Systemic therapy (topical therapy preferable)

  • Prednisolone p.o. 80-100 mg daily, if necessary shock therapy i.v. 500-1000 mg daily for 3 days
  • Methylprednisolone p.o. 60-80 mg 1x tgl.
  • Doxycyclin 1-2x 100mg daily 
  • Rituximab 
    • Two dosing schemes according to literature: autoimmune protocol: Two cycles of 1000 mg a day 0 and 14 first infusion: The recommended initial infusion rate is 50 mg/h; it can be gradually increased by 50 mg/h every 30 minutes after the first 60 minutes to a maximum of 400 mg/h every 50 minutes. Further infusions: Further infusions of Rituximab may be administered at an infusion rate of 100 mg/h. 
  • Methotrexate (MTX) s.c. 15 mg 1x weekly
    • Start with 10 mg 1x weekly, increasing weekly by 2.5 mg until 15 mg is reached. Folic acid p.o. 5 mg 1-0-0 the following day to reduce side effects
  • Azathioprine p.o. 1x tgl
    • Initially: 100-150 mg/kg bw
    • CAVE: With concomitant administration of allopurinol, a reduction of the azathioprine dose to a ¼ dose is indicated
  • Ciclosporin p.o. 3-5 mg/kg bw daily
    • Take independently of meals
  • Intravenous immunoglobulins i.v. 2g/ kg bw over 3 days, repeat monthly
    • Initial dose: 0.4-0.8 g/kg bw
    • In the course: 0.2 g/kg bw every 3 to 4 weeks
    • Determination of the IgG serum level always immediately before the next infusion!
    • An IgG valley level of at least 5 to 6 g/l should be reached before a new infusion
  • Light therapy is contraindicated!
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