Bullous pemphigoid

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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