What is bullous pemphigoid?

Bullous Pemphigoid

Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by autoantibodies directed against components of the basement membrane zone of the skin, primarily affecting elderly individuals with tense blisters, pruritus, and significant morbidity. 1

Definition and Pathophysiology

Bullous pemphigoid is caused by:

• Autoantibodies (mainly IgG, rarely IgA, IgM, and IgE) targeting components of the hemidesmosome adhesion complex 1
• Two main autoantigens: BP230 (BPAg1) and BP180 (BPAg2, collagen XVII) 1
• The antigen-antibody interaction results in subepidermal blister formation 1

Epidemiology

• Most common autoimmune blistering disease in Western countries 1
• Incidence: 43 per million per year in the UK; 7-13 per million in other parts of Europe 1
• Typically affects elderly patients (mean age of onset around 80 years) 1
• Equal distribution between sexes 1
• Significant association with neurological disorders including:
  • Dementia
  • Parkinson's disease
  • Cerebrovascular disease
  • Epilepsy
  • Multiple sclerosis 1

Clinical Presentation

The clinical presentation of BP is variable:

• Classic presentation: Tense blisters on erythematous or normal-appearing skin, primarily on limbs and trunk 1
• Pruritus is often severe and may precede blister formation by weeks or months 1
• In up to 20% of patients, bullae may be completely absent, with only:
  • Excoriations
  • Prurigo-like lesions
  • Eczematous lesions
  • Urticarial lesions
  • Infiltrated plaques 1
• Mucosal involvement (oral and genital) occurs in some patients 1
• Variant forms include dyshidrosiform BP (blisters on palms/soles) 2

Diagnosis

Diagnosis is established through a combination of:

1. Clinical features: Tense blisters, pruritus, urticarial plaques

2. Histopathology:

   • Biopsy from a fresh blister shows subepidermal clefting
   • Inflammatory infiltrate mainly consisting of eosinophils 1

3. Direct immunofluorescence (DIF):

   • Gold standard for diagnosis
   • Biopsy taken from uninvolved skin about 1 cm from a fresh blister
   • Shows linear deposits of IgG and/or C3 at the basement membrane zone 1

4. Indirect immunofluorescence (IIF):

   • Demonstrates circulating IgG antibodies binding in a linear pattern at the basement membrane
   • Salt-split skin technique helps differentiate BP from other subepidermal diseases 1

5. ELISA:

   • Measures serum levels of antibodies to BP180 and BP230
   • BP180 ELISA is more sensitive than BP230 ELISA
   • Antibody titers may correlate with disease activity 1

Differential Diagnosis

• Linear IgA disease
• Mucous membrane pemphigoid
• Epidermolysis bullosa acquisita
• Dermatitis herpetiformis
• Pemphigus vulgaris
• Contact dermatitis
• Insect bites
• Burns
• Erythema multiforme 1

Disease Course and Prognosis

• Usually self-limiting with a clinical course lasting from months to years 1
• Associated with significant morbidity and mortality (6-41%) 1
• Elderly patients are at high risk of adverse drug reactions and side effects from treatment 1

Management Considerations

The management of BP should be supervised by a dermatologist familiar with the condition, with consideration of:

1. Patient factors:

   • Age and general condition
   • Comorbidities (especially neurological and cardiovascular)
   • Risk of treatment-related adverse effects 1

2. Disease factors:

   • Extent and severity of disease
   • Presence of mucosal involvement
   • Impact on quality of life 1

3. Treatment goals:

   • Control of symptoms (especially pruritus)
   • Suppression of blister formation
   • Minimizing adverse effects of treatment 1

Emerging Research

Recent advances in understanding BP include:

• Distinct immune cell patterns in skin versus blister fluid (neutrophils predominate in blister fluid, while eosinophils are more prevalent in skin lesions) 3
• Emerging evidence that anti-BP230 antibodies may contribute directly to tissue damage 4
• Development of targeted therapies including biologics (rituximab, omalizumab, dupilumab) and JAK inhibitors 5

Bullous pemphigoid remains a challenging condition with significant impact on elderly patients' quality of life. Early diagnosis and appropriate management are essential to reduce morbidity and mortality associated with this disease.