How do I diagnose and initially treat bullous pemphigoid?

Diagnosis and Initial Treatment of Bullous Pemphigoid

The diagnosis of bullous pemphigoid requires a combination of clinical features, histopathology, and direct immunofluorescence microscopy, with initial treatment consisting of superpotent topical corticosteroids for localized disease and oral corticosteroids for generalized disease. 1, 2

Diagnostic Approach

Clinical Evaluation

• Patient History:

  • Document date of onset and evolution of symptoms
  • Note any recent drug intake (1-6 months prior), especially diuretics and psycholeptic drugs
  • Assess for comorbidities, particularly neurological disorders (dementia, Parkinson's disease) which are significantly associated with bullous pemphigoid 2
  • Consider bullous pemphigoid in elderly patients (>70 years) with unexplained persistent pruritus

• Physical Examination:

  • Look for characteristic features:
    • Tense bullae on erythematous or normal-appearing skin
    • Symmetric distribution (flexural surfaces of limbs, inner thighs, abdomen)
    • Absence of atrophic scarring
    • Absence of mucosal involvement
    • Absence of predominant bullous lesions on neck and head 1
  • Note that non-bullous forms occur in up to 20% of cases, presenting as excoriations, prurigo-like lesions, or eczematous lesions 2

Laboratory Confirmation

1. Skin Biopsy for Histopathology:

   • Take specimen from early bulla on erythematous skin
   • Look for subepidermal bullae containing eosinophils and/or neutrophils
   • Note dermal infiltrate of eosinophils/neutrophils or marginalization of eosinophils along dermoepidermal junction 1

2. Direct Immunofluorescence (DIF):

   • Essential for diagnosis with 93% positivity rate
   • Take biopsy from perilesional skin (1 cm away from lesion)
   • Look for linear deposits of IgG and/or C3 along the dermoepidermal junction 1, 2

3. Serological Tests:

   • Indirect immunofluorescence (IIF) on salt-split skin: IgG autoantibodies binding to epidermal side of split
   • ELISA for anti-BP180 and anti-BP230 antibodies (BP180 titers correlate with disease activity) 2

Initial Treatment Algorithm

For Localized Disease:

1. First-line: Superpotent topical corticosteroids (clobetasol propionate 0.05% cream/ointment)
   • Apply only to lesions twice daily until lesions heal
   • Continue for 2 weeks after healing
   • Gradually taper to less potent topical steroids for maintenance 2, 3

For Generalized Disease:

1. First-line: Oral corticosteroids (prednisolone)

   • Starting dose: 0.5-0.75 mg/kg/day (not exceeding 52.5 mg daily for a 70 kg patient)
   • Higher doses (>0.75 mg/kg/day) do not provide additional benefit 2, 4

2. Adjuvant Therapy (to reduce steroid dose):

   • First choice: Tetracycline (e.g., doxycycline) + nicotinamide
   • Second choice: Azathioprine (1-2.5 mg/kg/day) - check thiopurine methyltransferase before starting
   • Third choice: Dapsone (≤1.0 mg/kg/day) - check G6PD before starting 2

Monitoring and Follow-up

• Initial visits every 2 weeks until disease control
• Then monthly for 3 months, followed by every 2 months
• Monitor:
  • New lesion formation
  • Healing of established lesions
  • Treatment-related side effects
  • Blood pressure, CBC, liver and kidney function, glucose levels
  • Anti-BP180 IgG by ELISA (days 0,60,150) 2

Important Considerations

• Treatment should be supervised by a dermatologist familiar with the condition
• Consider less aggressive therapy for elderly patients with significant comorbidities
• Very potent topical steroids have shown better survival and disease control with fewer complications compared to oral steroids in extensive disease 4
• Most deaths reported in bullous pemphigoid are associated with high-dose oral corticosteroids 4
• Recognize that bullous pemphigoid has a chronic course with spontaneous exacerbations 5