Bullous Pemphigoid

Question 1

Definition

Answer 1

• Bullous pemphigoid is a chronic, acquired blistering disease characterised by auto-antibodies against hemidesmosomal antigens, resulting in the formation of a sub-epidermal blister.

Question 2

Aetiology

Answer 2

• Circulating and tissue bound autoantibodies against various components of the dermal-epidermal anchoring (hemidesmosomes of basal keratinocytes, anchoring filaments of the basement membrane and anchoring fibrils of the papillary dermis).
• Structural proteins within this complex, described as autoantigens, include bullous pemphigoid antigen 180, BP 230m alpha 6 beta 4 integrin, laminin 5 and 6, and type VII collagen.

Question 3

Signs & Symptoms

Answer 3

• Signs/symptoms include pruritis, tense blisters on normal or erythematous skin and erythematous or urticarial plaques.
• Risk factors include age 60-90 years, and MHC class II allele (DQB1*0301).

Question 4

Pathophysiology

Answer 4

• Autoantibodies are directed against 2 hemidesmosomal proteins, designated BP180 and BP230.
• Circulating auto antibodies, infiltration of inflammatory cells and the release of proteins and inflammatory mediators are responsible for injury.
• Binding of anti-BP120 antibody to its target is the critical first step in sub-epidermal blister formation.
• Bullous pemphigoid often provokes blood and tissue eosinophilia and eotaxin and IL-5 are strongly associated with this.

Question 5

Investigations

Answer 5

• Skin biopsy for histopathological evaluation with light microscopy
  o Sub-epidermal blister with dermal inflammatory cell infiltrate rich in eosinophils
• Skin biopsy for direct immunofluorescence testing
  o Linear band of IgG and/or C3 along basement membrane zone
• Indirect immunofluorescence test on serum
  o Positive titre for antibodies to bullous pemphigoid antigens

Question 6

Treatment

Answer 6

• Topical corticosteroids (i.e. clobetasol)
• Topical tacrolimus
• Sedating antihistamines
• Oral corticosteroids (i.e. prednisolone)
• Antibiotic therapy
• Plasmapheresis or IVIG and/or rituximab

Question 7

Complications

Answer 7

• Corticosteroid-induced osteoporosis
• Secondary infection
• Death

Question 8

Prevention & Prognosis

Answer 8

• Prognosis
  o Most patients go into remission with appropriate treatment
  o Mortality 6-41% in the first year among older people