What are the key differences between bullous pemphigoid and pemphigus vulgaris?

Key Differences Between Bullous Pemphigoid and Pemphigus Vulgaris

Bullous pemphigoid and pemphigus vulgaris are fundamentally distinct autoimmune blistering diseases that differ in their target antigens, blister location, clinical presentation, patient demographics, and prognosis.

Pathophysiology and Immunology

Bullous pemphigoid involves autoantibodies (IgG) directed against hemidesmosomes at the dermal-epidermal junction, specifically targeting BP180 and BP230 antigens, which causes a subepidermal split resulting in tense bullae 1, 2, 3.

Pemphigus vulgaris is characterized by IgG autoantibodies targeting desmoglein 3 (Dsg3), with 50-60% of patients also having Dsg1 antibodies, causing intraepithelial acantholysis that produces flaccid bullae 4, 5, 2, 3.

Clinical Presentation

Blister Characteristics

• Bullous pemphigoid: Tense, firm bullae on erythematous or normal-appearing skin that resist rupture 1, 3
• Pemphigus vulgaris: Flaccid, fragile bullae that rupture easily, leaving painful erosions 3

Distribution and Mucosal Involvement

• Bullous pemphigoid: Generalized or localized distribution typically sparing the head and neck; mucosal involvement is uncommon (occurs in minority of cases) 1
• Pemphigus vulgaris: Oral mucosa is the first site of involvement in the majority of cases, with oral erosions occurring in almost all patients; skin involvement follows after an average lag period of 4 months 4, 5

Associated Symptoms

• Bullous pemphigoid: Intense pruritus is a hallmark feature; up to 20% present with non-bullous variants including excoriations, prurigo-like lesions, or urticarial plaques 1
• Pemphigus vulgaris: Painful mucosal erosions are the predominant symptom, particularly affecting the palatal mucosa 5

Demographics and Epidemiology

• Bullous pemphigoid: Primarily affects elderly patients over 70 years of age, with significant association with neurological disorders including dementia, Parkinson's disease, and stroke 6, 1
• Pemphigus vulgaris: Peak frequency occurs in the third to sixth decades of life (ages 30-60), affecting a younger population 4, 5, 7

Histopathology

• Bullous pemphigoid: Subepidermal blister with eosinophils and/or neutrophils, plus dermal eosinophilic infiltrate that may marginalize along the dermo-epidermal junction 1
• Pemphigus vulgaris: Suprabasal acantholysis and intraepithelial blister formation 4, 5

Immunofluorescence Patterns

Direct Immunofluorescence (DIF)

• Bullous pemphigoid: Linear IgG and/or C3 deposition along the dermo-epidermal junction 1
• Pemphigus vulgaris: IgG deposition in the intercellular spaces of the epidermis in a "chicken wire" pattern; sensitivity of 89% in oral biopsies 4, 5

Indirect Immunofluorescence (IIF)

• Bullous pemphigoid: IgG binding to the epidermal side on salt-split skin 1
• Pemphigus vulgaris: Circulating IgG antibodies against keratinocyte cell surface 4, 2

Prognosis and Mortality

• Bullous pemphigoid: Mortality is roughly twice that of age-matched general elderly population during active phase; high-dose systemic corticosteroids (>40mg prednisolone daily) double mortality risk 6, 1
• Pemphigus vulgaris: Historically 75% mortality before corticosteroids; current mortality varies by phenotype: 1-17% for predominantly mucosal disease versus 34-42% for mucocutaneous disease; approximately 3 times higher mortality than general population 4, 5, 7

Treatment Approach Differences

Bullous Pemphigoid

Superpotent topical corticosteroids (clobetasol propionate 0.05% cream) are first-line treatment, providing superior disease control with significantly lower mortality compared to systemic corticosteroids 6, 1. For patients unable to apply topical steroids, doxycycline 200mg/day combined with nicotinamide achieves 73.8% response rate 6.

Pemphigus Vulgaris

Systemic corticosteroids are the mainstay of treatment, typically combined with adjuvant immunosuppressive drugs for steroid-sparing effect 4. Rituximab has recently emerged as the drug of choice for most patients 3.

Critical Diagnostic Pitfalls

• Pemphigus vulgaris may be misdiagnosed when oral lesions precede cutaneous involvement by months, potentially being confused with other oral conditions 5
• Bullous pemphigoid non-bullous variants (20% of cases) presenting only with refractory pruritus or excoriations can delay diagnosis 1
• Approximately 50% of drug-induced bullous pemphigoid cases persist after drug withdrawal and require conventional treatment 6, 1
• Rare cases of dual diagnosis with features of both diseases have been reported, requiring long-term high-dose immunosuppression with poor prognosis 8