Bullous Diseases: Pemphigus vs Pemphigoid
A high-yield Step 1 comparison of pemphigus vulgaris (anti-desmoglein 3, intraepidermal/suprabasal split, flaccid bullae, Nikolsky positive, "fishnet" DIF) versus bullous pemphigoid (anti-BP180/BP230, subepidermal split, tense bullae, Nikolsky negative, linear IgG+C3 DIF), built around board vignettes, biopsy/immunofluorescence buzzwords, and next-best-step management.
The one question that splits every blister
Bullous diseases turn on a single question the boards love: where does the skin separate?
In pemphigus vulgaris (PV), IgG autoantibodies attack desmoglein 3 (± desmoglein 1), the desmosomal cadherins that glue keratinocytes to each other. Loss of cell–cell adhesion (acantholysis) produces an intraepidermal, suprabasal split — so blisters are flaccid and rupture easily.
In bullous pemphigoid (BP), IgG targets the hemidesmosome proteins BP180 (collagen XVII) and BP230, which anchor basal keratinocytes down to the basement membrane. The split is subepidermal, so blisters are tense and stay intact.
Both are type II hypersensitivity reactions. That one anatomic difference — intraepidermal vs subepidermal — predicts the morphology, the Nikolsky sign, the biopsy, the immunofluorescence pattern, and even the prognosis. Learn the split and the rest falls out.
Pemphigus vulgaris (deeper problem, sicker patient)
- Autoantibodies vs desmoglein 3 (±1) → intraepidermal / suprabasal split
- Flaccid bullae that slough into painful erosions
- Oral / mucosal lesions are common and often the first sign ("pemphi-GUMS")
- Nikolsky sign POSITIVE — light lateral pressure shears the epidermis
- Middle age (30–60); potentially fatal untreated (fluid loss, sepsis)
Bullous pemphigoid (more benign)
- Autoantibodies vs BP180 / BP230 hemidesmosomes → subepidermal split
- Tense, intact bullae on urticarial / erythematous skin; intensely pruritic
- Nikolsky sign NEGATIVE; mucosa usually spared
- Elderly (>60–70); flexural sites — groin, axillae, inner thighs, flexor forearms, lower abdomen
Pemphigus vulgaris vs bullous pemphigoid
| Feature | Pemphigus vulgaris | Bullous pemphigoid |
|---|---|---|
| Target antigen | Desmoglein 3 (±1) — desmosome | BP180 / BP230 — hemidesmosome |
| Level of split | Intraepidermal (suprabasal) | Subepidermal |
| Blister | Flaccid, ruptures → erosions | Tense, intact |
| Nikolsky sign | Positive | Negative |
| Oral / mucosa | Commonly involved, often first | Usually spared |
| Symptom | Painful erosions | Intense pruritus |
| Typical age | 30–60 | >60–70 (elderly) |
| Histology | Acantholysis, "row of tombstones" | Subepidermal blister + eosinophils |
| DIF pattern | Intercellular "fishnet" IgG | Linear IgG + C3 at BMZ |
| Prognosis | Severe, can be fatal | More benign |
| First-line Rx | Systemic steroids ± rituximab | Topical / systemic steroids |
Vignette: A 48-year-old has weeks of painful oral erosions, then flaccid blisters on the trunk and scalp that rupture into raw, weeping erosions. Gentle lateral pressure on normal-appearing skin sloughs the epidermis (Nikolsky positive). Lesions are painful, not itchy.
Most likely diagnosis: Pemphigus vulgaris
Best diagnostic step:
- Lesional skin biopsy (H&E) → suprabasal acantholysis, retained basal cells = "row of tombstones"
- Perilesional direct immunofluorescence (DIF) → intercellular net-like / "fishnet" IgG
- Serum anti-desmoglein 3/1 ELISA supports the dx and tracks activity
Next best step in management: systemic corticosteroids (first-line); add rituximab ± steroid-sparing agents (azathioprine, mycophenolate) for moderate–severe disease.
Board trap: painful mouth sores preceding skin blisters + positive Nikolsky = PV, not BP.
Vignette: A 75-year-old has intensely itchy, tense, fluid-filled bullae on the flexor forearms, inner thighs, and lower abdomen, arising on urticarial plaques. The oral mucosa is clear. Rubbing perilesional skin does not induce a blister (Nikolsky negative).
Most likely diagnosis: Bullous pemphigoid
Best diagnostic step:
- Perilesional DIF → linear IgG and C3 along the basement membrane (the key test)
- Biopsy → subepidermal blister packed with eosinophils
- Serum anti-BP180 ELISA
Next best step in management:
- Localized: high-potency topical corticosteroid (clobetasol) — trials show it matches oral steroids with fewer complications in the elderly
- Widespread: systemic corticosteroids; doxycycline ± nicotinamide or azathioprine/MMF as steroid-sparing
Board trap: elderly + tense pruritic bullae + spared mouth + Nikolsky − = BP.
- Perilesional (NOT lesional) skin is the correct sample for DIF — the diagnostic gold standard for both diseases
- PV DIF: intercellular "fishnet" / "chicken-wire" IgG throughout the epidermis
- BP DIF: smooth linear band of IgG + C3 at the dermoepidermal junction
- PV histology: suprabasal acantholysis; retained basal keratinocytes = "row of tombstones"; free rounded acantholytic (Tzanck) cells
- BP histology: subepidermal blister rich in eosinophils
- Serology tracks activity: anti-desmoglein 1/3 (PV) vs anti-BP180/BP230 (BP)
- Salt-split skin: BP antibodies bind the roof (epidermal side) — contrast epidermolysis bullosa acquisita, which binds the dermal floor
Pemphigus vulgaris
- First-line: systemic corticosteroids
- Rituximab (anti-CD20) is now a first-line adjunct for moderate–severe PV
- Steroid-sparing: azathioprine, mycophenolate mofetil
- Treat as an emergency — untreated mortality from sepsis and fluid/electrolyte loss
Bullous pemphigoid
- Localized: high-potency topical steroid (clobetasol) preferred
- Widespread: systemic corticosteroids ± doxycycline + nicotinamide, azathioprine/MMF
- Frequently associated with neurologic disease (dementia, Parkinson disease, stroke)
Both
- Wound care and monitoring for secondary bacterial infection
- Review meds: PV can be drug-induced (thiol drugs — penicillamine, captopril); BP is drug-associated (gliptins/DPP-4 inhibitors, loop diuretics)
- Pemphigus = Positive Nikolsky, Painful, Poor prognosis — intraepidermal, flaccid
- Pemphi-GUS → think GUMS: oral/mucosal involvement is common and often the first sign
- "Row of tombstones" = pemphigus histology (basal keratinocytes still lined up on the basement membrane)
- Bullous Pemphigoid = Below, Big, Bullae stay, Benign(er), BP180 — subepidermal, tense blisters that stay intact
- Fishnet = pemphigus (intercellular IgG) vs Linear = pemphigoid (IgG + C3 at the basement membrane)
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