What are the clinical features and treatment options for bullous pemphigoid?

Clinical Features of Bullous Pemphigoid

Bullous pemphigoid (BP) is characterized by tense blisters on erythematous or normal-appearing skin, often preceded by pruritic urticarial or eczematous lesions that may present weeks to months before blister formation. 1

Key Clinical Features

Primary Cutaneous Manifestations

• Tense bullae/blisters:
  • Arise on either erythematous or normal-appearing skin
  • Primarily affect limbs and trunk
  • Can be widespread or localized 2, 1
• Prodromal phase:
  • Pruritus (ranging from mild to intense)
  • Urticarial or eczematous rash
  • May precede blister formation by weeks, months, or occasionally years 2, 1
• Distribution:
  • Predominantly affects trunk and extremities
  • Flexural areas commonly involved 1

Mucosal Involvement

• Oral lesions occur in approximately 10-30% of patients
• Present as small blisters or erosions
• Primarily affect palatal mucosa 2
• Genital mucosa may also be affected 2

Atypical Presentations

• Localized forms
• Pruritus without visible blisters
• Erythema annulare centrifugum-like presentation (rare) 3
• Nodular, vegetating, erythrodermic, or erosive variants 4

Pathophysiology and Associations

Immunopathology

• Autoantibodies (primarily IgG) target:
  • BP180 (collagen XVII)
  • BP230 antigens in the hemidesmosomal complex 1
• Linear deposits of IgG and/or C3 at the basement membrane zone on direct immunofluorescence 2
• Subepidermal clefting with eosinophil-rich inflammatory infiltrate on histopathology 2

Associated Conditions

• Strong association with neurological disorders:
  • Dementia
  • Parkinson's disease
  • Cerebrovascular disease
  • Multiple sclerosis
  • Epilepsy 2, 1
• Potential drug associations:
  • Furosemide
  • Spironolactone
  • Neuroleptics
  • Gliptins in diabetic patients 2

Diagnostic Approach

Laboratory Diagnosis

1. Skin biopsy for histopathology:

   • From a fresh blister
   • Shows subepidermal cleft with mixed inflammatory infiltrate containing numerous eosinophils 2

2. Direct immunofluorescence:

   • Perilesional skin (1 cm from lesion)
   • Shows linear deposits of IgG and/or C3 at the basement membrane zone 2

3. Serological testing:

   • Indirect immunofluorescence to detect circulating autoantibodies
   • ELISA for anti-BP180 and anti-BP230 antibodies (BP180 ELISA more sensitive) 2, 1

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 2

Treatment Approach

First-Line Treatment

• For localized/mild disease:

  • Superpotent topical corticosteroids (clobetasol propionate 0.05%)
  • Applied to affected areas or whole body except face 1

• For generalized disease:

  • Oral corticosteroids (prednisolone) at 0.5-0.75 mg/kg/day
  • Higher doses provide no additional benefit 1

Second-Line and Adjunctive Options

• Tetracycline plus nicotinamide
• Dapsone (after G6PD testing)
• Azathioprine (after checking thiopurine methyltransferase)
• Topical immunomodulators (e.g., tacrolimus) 1

Refractory Disease

• Anti-CD20 monoclonal antibodies (rituximab)
• Anti-IgE monoclonal antibodies (omalizumab)
• Intravenous immunoglobulins
• Cyclophosphamide 1, 5

Disease Course and Prognosis

• Generally self-limiting disease
• Usually remits within 5 years
• Mortality rates between 6-41% in the modern era 2, 1
• Elderly patients at high risk for treatment-related adverse effects 2

Special Considerations

• Regular monitoring of disease activity and treatment-related side effects is essential
• Patients with ocular, laryngeal, or esophageal involvement require urgent specialist consultation
• Elderly patients often have comorbidities requiring careful treatment planning 1
• Newer targeted therapies (biologics, JAK inhibitors) may reduce adverse effects associated with conventional treatments 5