Bullous Pemphigoid

Risk factors

• Age >70
• Neurodegenerative disease (Parkinson, Alzheimer dementia, stroke, MS)
• Drugs: DPP-4 inhibitors (sitagliptin, linagliptin, vildagliptin), PD-1/PD-L1 inhibitors, furosemide, penicillins, sulfasalazine
• Recent UV exposure or radiotherapy (can trigger localized disease)

Pathophysiology

IgG autoantibodies bind BP180 (collagen XVII) at the NC16A domain and BP230 within the hemidesmosomal plaque. Complement activation, mast cell degranulation, and eosinophil recruitment release proteases that cleave the lamina lucida, producing subepidermal separation with preservation of the overlying epidermis (hence tense, intact bullae).

Clinical presentation

Differential diagnosis

• Pemphigus vulgaris — Flaccid bullae, almost-universal painful oral erosions, positive Nikolsky, intraepidermal split, anti-desmoglein antibodies
• Dermatitis herpetiformis — Intensely pruritic grouped vesicles on extensor surfaces in young adults; associated with celiac; granular IgA at dermal papillae
• Epidermolysis bullosa acquisita — Blisters on trauma-prone sites, milia, scarring; antibodies to type VII collagen; salt-split skin binds dermal side
• Linear IgA bullous dermatosis — "String of pearls" annular vesicles; vancomycin a common trigger; linear IgA at basement membrane on DIF
• Bullous drug eruption / SJS/TEN — Acute onset after offending drug; targetoid lesions, mucosal involvement, full-thickness epidermal necrosis on biopsy
• Bullous arthropod reaction — Localized clustered tense vesicles on exposed skin; preceding bite history; eosinophilic dermal infiltrate without antibody deposition

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A["Elderly patient with<br/>itch ± tense bullae"] --> B["Skin biopsy x2:<br/>lesional H&E +<br/>perilesional DIF"]
  B --> C{"DIF: linear<br/>IgG/C3 at BMZ?"}
  C -->|Yes| D["Serum anti-BP180/BP230<br/>ELISA"]
  C -->|No| E["Consider PV, DH,<br/>EBA, LABD"]
  D --> F{Disease extent}
  F -->|Localized / mild| G["Clobetasol 0.05%<br/>applied to lesions<br/>± doxycycline"]
  F -->|Moderate-extensive| H["Whole-body clobetasol 0.05%<br/>or prednisone 0.5 mg/kg/day<br/>± steroid-sparing agent"]
  H --> I{Refractory?}
  I -->|Yes| J["Dupilumab (FDA 2025),<br/>rituximab, omalizumab, IVIG"]
  I -->|No| K[Slow taper<br/>over months]

Treatment

Complications

• Secondary bacterial infection, cellulitis, sepsis
• Steroid morbidity in elderly: hyperglycemia, osteoporosis, fractures, delirium
• Increased 1-year mortality (10-40% in elderly with comorbidities), often from infection or cardiovascular events rather than the disease itself
• Recurrence after taper of therapy

PANCE pearls

• Non-bullous prodromal phase can mimic chronic urticaria, scabies, or eczema for months before blisters appear; high index of suspicion in elderly patients with intractable itch.
• Salt-split skin direct immunofluorescence distinguishes BP (epidermal/roof side) from epidermolysis bullosa acquisita (dermal/floor side).
• Whole-body clobetasol is genuinely first-line for many elderly patients and avoids systemic steroid morbidity.
• DPP-4 inhibitors — especially linagliptin and vildagliptin — are now a recognized iatrogenic trigger; switch class if BP develops.
• Strong association with neurologic disease; ask about Parkinson disease, dementia, or stroke.

References

• EADV 2022 — Borradori L et al., Updated S2K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (JEADV 2022;36(10):1689-1704)
• Joly NEJM 2002 — A comparison of oral and topical corticosteroids in patients with bullous pemphigoid (Joly et al., NEJM 2002)
• BLISTER Trial — Williams HC et al., Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial (Lancet 2017;389:1630-38)