What are the diagnostic criteria and treatment options for bullous pemphigoid?

Bullous Pemphigoid Diagnosis and Treatment

Bullous pemphigoid diagnosis requires a combination of clinical presentation, histopathology showing subepidermal clefts with eosinophils, direct immunofluorescence demonstrating linear IgG/C3 deposits at the basement membrane zone, and serological testing for anti-BP180/BP230 antibodies. 1

Diagnostic Criteria

Clinical Presentation

• Tense bullae/blisters on erythematous or normal-appearing skin, primarily on limbs and trunk
• Prodromal phase with pruritus and urticarial or eczematous rash (may precede blisters by weeks to years)
• Oral lesions in 10-30% of patients (small blisters or erosions, mainly on palatal mucosa)
• Genital mucosa involvement in some cases 1

Diagnostic Tests

1. Skin biopsy for histopathology

   • Shows subepidermal cleft with mixed inflammatory infiltrate containing numerous eosinophils 1

2. Direct immunofluorescence (DIF)

   • Gold standard with 93% positivity rate
   • Shows linear deposits of IgG and/or C3 at the basement membrane zone 1

3. Serological testing

   • Indirect immunofluorescence to detect circulating autoantibodies
   • ELISA for anti-BP180 and anti-BP230 antibodies 1, 2
   • Multivariant ELISA systems provide practical screening tools 2

4. Salt-split skin technique

   • Differentiates BP from epidermolysis bullosa acquisita and cicatricial pemphigoid
   • In BP, antibodies bind to the roof of the artificial blister 1

Clinical Pearl: Diagnosis may be challenging in atypical or non-bullous presentations with only pruritic, eczematous, or urticarial lesions. Maintain high suspicion in elderly patients with persistent unexplained pruritus. 3

Treatment Options

Mild/Localized Disease

• First-line: Superpotent topical corticosteroids (clobetasol propionate 0.05% cream/ointment)
  • Apply twice daily until lesions heal
  • Continue for 2 weeks after healing, then taper
  • Can be applied to affected areas only for localized disease 1, 4

Generalized Disease

• First-line: Oral corticosteroids (prednisolone)
  • Dosage: 0.5-0.75 mg/kg/day (higher doses provide no additional benefit)
  • Consider less aggressive therapy for patients with significant comorbidities 1

Second-line Options

• Tetracycline + nicotinamide
• Dapsone (after G6PD testing)
• Topical immunomodulators (e.g., tacrolimus) 1

Third-line/Resistant Cases

• Anti-CD20 monoclonal antibodies (rituximab)
• Anti-IgE monoclonal antibodies (omalizumab)
• Newer biologics (dupilumab)
• JAK inhibitors
• Intravenous immunoglobulins
• Immunoadsorption
• Plasma exchange
• Cyclophosphamide 1, 5

Monitoring and Follow-up

• Regular monitoring of disease activity:

  • New lesion formation
  • Healing of established lesions
  • Treatment-related side effects
  • Disease progression to other mucosal sites 1

• Follow-up schedule:

  • Every 2 weeks until disease control
  • Monthly for next 3 months
  • Every 2 months thereafter until treatment is stopped 1

Special Considerations

• Elderly patients: High risk for treatment-related adverse effects; consider less aggressive therapy 1

• Associated conditions: Be aware of associations with neurological disorders (dementia, Parkinson's, stroke), cardiovascular diseases, and certain medications (furosemide, spironolactone, neuroleptics, gliptins) 1

• Mucosal involvement: Urgent specialist consultation for ocular (ophthalmology), laryngeal (ENT), or esophageal (gastroenterology) involvement 1

• Disease assessment: Use Bullous Pemphigoid Disease Area Index (BPDAI) to standardize scoring of disease extent and activity 1

Important caveat: Diagnosis can be particularly challenging in atypical presentations, such as the ecthyma-gangrenosum-like variant seen in elderly, immobile patients with truncal lesions and bacterial colonization. Repeated diagnostic procedures may be necessary in these cases. 6