STEPTRACKERSKIN | PATHOLOGY + IMMUNOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Blistering Diseases

Where the skin splits decides the blister — and the antibody, drug or toxin that split it.

FOCUS ON
Pemphigus vulgaris: anti-desmoglein (desmosome), intraepidermal, flaccid bullae, mouth involved, Nikolsky ⁺, fishnet IF. Bullous pemphigoid: anti-hemidesmosome, subepidermal, tense bullae, elderly, mouth spared, linear IF, eosinophils. Dermatitis herpetiformis: celiac, IgA in dermal papillae. SJS/TEN: drug-induced epidermal necrosis with mucosal involvement.
DISORDER
MECHANISM · TARGET
FEATURES
CLUE · TREATMENT
Pemphigus vulgaris
Type II: IgG against desmoglein 3 (± 1) in desmosomes → acantholysis; drugs: penicillamine, captopril
Middle-aged; flaccid bullae and erosions; oral mucosa first; Nikolsky ⁺; suprabasal split, "tombstone" basal cells
IF: intercellular "fishnet" IgG · steroids, rituximab
Pemphigus foliaceus
IgG against desmoglein 1 (upper epidermis)
Superficial crusted erosions on face, scalp, trunk; no mucosal lesions
Split just below stratum corneum
Bullous pemphigoid
Type II: IgG against BP180/BP230 in hemidesmosomes → subepidermal split
Elderly; itchy urticarial plaques → tense bullae; mouth usually spared; Nikolsky ⁻; eosinophils
IF: linear IgG/C3 along basement membrane · topical/systemic steroids
Mucous membrane pemphigoid
Antibodies to basement membrane antigens of mucosa
Oral and ocular erosions → conjunctival scarring, blindness
Scarring variant
Dermatitis herpetiformis
IgA against epidermal transglutaminase; celiac disease
Intensely itchy grouped vesicles on elbows, knees, buttocks; neutrophil microabscesses at dermal papillae tips
IF: granular IgA in dermal papillae · dapsone + gluten-free diet
Erythema multiforme
Type IV reaction; HSV (most), Mycoplasma
Target lesions on extremities, palms, soles; minor (no/limited mucosa) or major
Recurs with HSV · acyclovir prophylaxis
Stevens-Johnson / TEN
Cytotoxic T cells kill keratinocytes (Fas-FasL, granulysin) after drugs: sulfonamides, allopurinol, anticonvulsants, NSAIDs, nevirapine
Fever, painful skin, mucosal erosions, full-thickness epidermal necrosis; SJS < 10% BSA, TEN > 30%; Nikolsky ⁺
Stop the drug · burn-unit care · carbamazepine + HLA-B*15:02
Staphylococcal scalded skin syndrome
Exfoliative toxin cleaves desmoglein 1
Infants/young children; fever, diffuse erythema, superficial sloughing; Nikolsky ⁺; mucosa spared
Split in granular layer · antistaphylococcal antibiotics
Porphyria cutanea tarda
↓ uroporphyrinogen decarboxylase; triggered by HCV, alcohol, iron, estrogen
Blisters and fragility on sun-exposed hands, hypertrichosis, scarring
Tea-colored urine (uroporphyrin) · phlebotomy, hydroxychloroquine
Epidermolysis bullosa
Inherited structural protein defects (keratin 5/14, laminin, collagen VII)
Blisters from minor friction since infancy; scarring in dystrophic forms
Dystrophic type → SCC risk

Mechanism — level of the split

Granular layerSSSS, pemphigus foliaceus (Dsg1)
↓
SuprabasalPemphigus vulgaris (Dsg3)
↓
Basement membraneBullous pemphigoid (hemidesmosome)
↓
Dermal papillaeDermatitis herpetiformis (IgA)

Intraepidermal blisters have thin roofs (flaccid, rupture, Nikolsky ⁺); subepidermal blisters have full-thickness roofs (tense).

Pemphigus vs pemphigoid

FEATURE
PEMPHIGUS VULGARIS
BULLOUS PEMPHIGOID
Target
Desmosome (desmoglein)
Hemidesmosome (BP180/230)
Split
Intraepidermal (suprabasal)
Subepidermal
Blister
Flaccid, erosions
Tense
Mucosa
Involved (often first)
Usually spared
Nikolsky
Positive
Negative
IF
Intercellular fishnet
Linear at BM
Age
40–60
Elderly

How it's tested

COMMON CONFUSIONSSSS and TEN both peel with a positive Nikolsky sign. SSSS: child, toxin, granular-layer split, no mucosa. TEN: drug, full-thickness necrosis, mucosa involved.
THE TRAPMouth ulcers before skin blisters point to pemphigus vulgaris, not pemphigoid — and the oral lesions are often misread as aphthous ulcers.
YOUR APPROACHFlaccid or tense → mucosa → Nikolsky → age, drugs, infections, celiac → biopsy with direct IF pattern → treatment.

If you see… think…

Painful oral erosions then flaccid skin bullae, Nikolsky⁺ → pemphigus vulgaris
Fishnet IgG on direct immunofluorescence → pemphigus
80-year-old with itchy tense blisters, mouth spared → bullous pemphigoid
Linear IgG along the basement membrane → bullous pemphigoid
Itchy vesicles on elbows + diarrhea → dermatitis herpetiformis (celiac)
Target lesions after a cold sore → erythema multiforme (HSV)
Fever, mouth and eye erosions, skin sloughing after lamotrigine → SJS/TEN
Febrile 2-year-old with sheets of peeling skin, mouth normal → staphylococcal scalded skin
HCV patient with blisters on the backs of the hands → porphyria cutanea tarda
Blisters with minimal friction since birth → epidermolysis bullosa