Summary

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, predominantly affecting elderly individuals. It is characterised by tense, subepidermal blisters on an erythematous or urticarial base, caused by IgG autoantibodies targeting hemidesmosomal proteins (BP180 and BP230) at the dermal-epidermal junction. Unlike pemphigus, blisters are tense and do not rupture easily, and Nikolsky sign is negative. The disease causes significant morbidity with intense pruritus, skin fragility, and risk of secondary infection. Treatment is with potent topical corticosteroids (first-line) or systemic immunosuppression for severe cases. Prognosis is generally good with treatment, but elderly patients have increased mortality due to treatment side effects and comorbidities.

Key Facts

• Epidemiology: Incidence 4-22 per million/year; increases exponentially with age
• Mean age of onset: 75-80 years
• Target antigens: BP180 (type XVII collagen) and BP230
• Blister type: Tense, subepidermal (vs flaccid in pemphigus)
• Nikolsky sign: Negative (epidermis intact)
• Immunofluorescence: Linear IgG and C3 at basement membrane zone
• First-line treatment: Very potent topical corticosteroids (clobetasol propionate)
• Prognosis: Chronic, relapsing-remitting; most remit within 5 years
• Mortality: 1-year mortality 20-40% (elderly, comorbidities, treatment side effects)
• Drug-induced: DPP-4 inhibitors (gliptins), PD-1 inhibitors increasingly recognised

Clinical Pearls

"Tense vs Flaccid Rule": Bullous pemphigoid has TENSE blisters (subepidermal; epidermis intact) while pemphigus has FLACCID blisters (intraepidermal; fragile roof). This clinical distinction is key before biopsy.

"The Urticarial Phase": BP often presents with pruritic urticarial plaques for weeks before blisters appear. Consider BP in elderly patients with new urticaria that doesn't respond to antihistamines.

"Topical First": The landmark BLISTER trial showed whole-body potent topical steroids are MORE effective than oral prednisolone with FEWER side effects. Topical is first-line even in extensive disease.

"Gliptin Alert": DPP-4 inhibitors (sitagliptin, linagliptin) are increasingly recognised as triggers of BP. Always check drug history and consider stopping the culprit.

"Beware the Comorbidity": BP patients are elderly with comorbidities. Mortality is driven by treatment complications (infections, falls, metabolic effects) more than the disease itself.

Why This Matters Clinically

Bullous pemphigoid causes significant morbidity in a vulnerable elderly population. Intense pruritus impairs sleep and quality of life. Large blisters and erosions are painful and prone to infection. Accurate diagnosis avoids inappropriate treatment, while optimal management balances disease control with minimising treatment toxicity. Recognition of drug-induced cases can lead to cure by stopping the offending agent.[1,2]

Structured Approach

General Inspection:

• Overall condition and frailty
• Nutritional status
• Signs of sepsis or systemic illness

Skin Examination:

• Distribution and extent of blisters (calculate %BSA)
• Character of blisters (tense vs flaccid)
• Base (erythematous, urticarial, normal skin)
• Presence of erosions, crusting
• Signs of secondary infection (purulence, cellulitis)
• Nikolsky sign testing

Mucosal Examination:

• Oral cavity: blisters, erosions, bleeding gums
• Eyes: conjunctival involvement
• Genital mucosa

Documentation:

• Photograph lesions (with consent)
• Record BSA affected
• Disease activity scoring (BPDAI if available)

Special Signs

Severity Scoring (BPDAI)

Natural History

Mortality

Prognostic Factors

Key Guidelines

Landmark Trials

BLISTER Trial (2017)

• RCT: 132 patients, clobetasol propionate vs prednisolone (0.5 mg/kg)
• Result: Topical clobetasol non-inferior and associated with fewer severe adverse events
• 1-year mortality: 24% topical vs 19% oral (not significant)
• Favours topical steroids as first-line
• PMID: 28215660

Joly et al. (2002)

• French RCT: Topical clobetasol vs oral prednisone (1 mg/kg)
• Topical was more effective with fewer side effects
• PMID: 12126322

Kirtschig et al. Cochrane Review (2010)

• Systematic review of treatments for BP
• Confirmed potent topical steroids effective; lower side effects than oral
• PMID: 20927719

Evidence Strength

What is Bullous Pemphigoid?

Bullous pemphigoid (BP) is a skin condition that causes large, itchy blisters. It mainly affects older adults, usually over 70 years old. It is not contagious—you cannot catch it from someone else or pass it on.

Why does it happen?

In BP, the immune system mistakenly attacks the layer that holds your skin together. This causes fluid to collect between the skin layers, forming blisters. We don't always know why this happens, but some medications can trigger it.

What are the symptoms?

• Severe itching (often the first symptom)
• Red, raised patches or hives-like areas
• Large blisters, usually on the arms, legs, and trunk
• Blisters are firm and don't break easily
• Mouth or eye involvement is rare

How is it treated?

The main treatment is a very strong steroid cream (clobetasol) applied to the skin. This is very effective and has fewer side effects than steroid tablets. For severe cases, steroid tablets or other medications may be needed.

Treatment usually continues for several months. Most people get better, but the condition can come back.

What to expect?

• Most people improve with treatment
• Blisters heal without scarring (unless infected)
• Treatment may take weeks to months
• It may come back (relapse) after stopping treatment
• Regular follow-up is needed

When to seek help

See a doctor urgently if you notice:

• Spreading redness around blisters (may be infection)
• Fever or feeling very unwell
• New blisters spreading rapidly
• Blisters in the mouth or eyes

High-Yield Exam Topics

Sample Viva Questions

Q1: An 80-year-old presents with widespread tense blisters. How do you investigate?

Model Answer: Clinical examination suggests bullous pemphigoid (elderly, tense subepidermal blisters). I would perform a skin biopsy for H&E (expect subepidermal blister with eosinophils) and a perilesional biopsy for direct immunofluorescence (expect linear IgG and C3 at the basement membrane zone). I would also request serology for BP180 and BP230 antibodies (ELISA), which confirm the diagnosis and can be used for monitoring. Baseline bloods including FBC (eosinophilia common), renal and liver function, and glucose are important before starting treatment.

Q2: What is the first-line treatment for extensive bullous pemphigoid?

Model Answer: The first-line treatment is very potent topical corticosteroids — specifically clobetasol propionate 0.05% applied to the entire body (20-40 g/day), based on the BLISTER and Joly trials. This is MORE effective than oral prednisolone and associated with fewer severe adverse events. Even in extensive disease, topical steroids should be tried first. Oral steroids (prednisolone 0.3-0.5 mg/kg) are reserved for cases refractory to topical treatment or where application is impractical.

Q3: How do you distinguish bullous pemphigoid from pemphigus vulgaris clinically?

Model Answer: Key differences include:

1. Blister character: BP has tense blisters that don't rupture easily (subepidermal); PV has flaccid blisters that rupture early leaving erosions (intraepidermal).
2. Nikolsky sign: Negative in BP; Positive in PV.
3. Mucosal involvement: Rare in BP (<20%); common in PV (>50%).
4. Age: BP affects elderly (>70); PV middle-aged (40-60).
5. Prognosis: BP generally good; PV more serious.

Definitive distinction requires biopsy: DIF shows linear IgG/C3 at BMZ in BP vs intercellular (chicken-wire) pattern in PV.

Common Exam Errors

Last Reviewed: 2025-12-24 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.