Autoimmune blistering diseases

Blistering diseases differential diagnostics

Disease	Pathophysiology / Target Antigen	Clinical Features & Morphology	Histology / Immunofluorescence (IF)
Pemphigus Vulgaris	IgG against Desmoglein 1 & 3 (Desmosomes) (Type II H.S.)	Flaccid bullae; rupture easily. Oral mucosa involved (often 1st). Nikolsky (+).	Intraepidermal split. ”Row of tombstones” on basalis. IF: Net-like / Reticular IgG pattern.
Bullous Pemphigoid	IgG against Hemidesmosomes (BP180/BP230) (Type II H.S.)	Tense bullae; do not rupture easily. Oral mucosa spared. Nikolsky (-).	Subepidermal split. Prominent Eosinophils. IF: Linear IgG at basement membrane.
Dermatitis Herpetiformis	IgA against Tissue Transglutaminase (Cross-reacts w/ reticulin)	Pruritic papules/vesicles on extensor surfaces (elbows, knees). Assoc: Celiac Disease.	Microabscesses (neutrophils) at dermal papillae tips. IF: Granular IgA at dermal papillae.
Epidermolysis Bullosa	Hereditary defect in anchoring proteins. (e.g., Keratin 5/14 or Collagen VII)	Blisters induced by minor trauma/friction. Presents in infancy/childhood.	Cleavage at Dermal-Epidermal Junction (DEJ). Electron microscopy used for subtypes.
Bullous Impetigo	Exfoliative Toxin A (S. aureus) cleaves Desmoglein 1.	Flaccid bullae with honey-colored crust. Rapid spread; contagious. Nikolsky (+).	Subcorneal split (very superficial). Gram stain: Gram (+) cocci in clusters.

Condition	Target/Cause	Split Location	Mucosal?	Nikolsky?	Key Buzzword
SJS/TEN	Drugs	DEJ (Full necrosis)	YES	(+)	Sloughing skin, >30% BSA (TEN)
SSSS	S. aureus Toxin	Granulosum (Superficial)	NO	(+)	Newborns, Desmoglein-1 split
Pemphigus Vulgaris	Anti-Desmoglein	Suprabasal	YES	(+)	Reticular IF, Tombstone, Flaccid
Bullous Pemphigoid	Anti-Hemidesmosome	Subepidermal	No/Rare	(-)	Linear IF, Tense Bullae
Dermatitis Herp.	Gluten (IgA)	Dermal Papillae	No	N/A	Pruritic, Extensors, Celiac

Link to original

Bullous pemphigoid

---

Etiology

• Type II hypersensitivity reaction
• Antihemidesmosome antibodies (IgG)

Clinical findings

• Large, tense, subepidermal blisters on normal, erythematous, or erosive skin
• Intensely pruritic lesions, possibly hemorrhagic, heal without scar formation
• Distributed on palms, soles, lower legs, groin, and axillae
• Oral involvement is rare

Diagnostics

• Tzanck test, Nikolsky sign: negative
• Histology and immunohistochemistry
  • Subepidermal vesicle formation
  • Eosinophil-rich infiltrate in underlying dermis
  • Immunofluorescence: deposition of linear IgG and C3 along the dermo-epidermal junction

Prognosis

• Benign disease, usually responds well to treatment
  • Blisters are deeper and more robust

Pemphigus vulgaris

---

Etiology

• Type II hypersensitivity reaction
• IgG antibodies directed against desmoglein 3 and desmoglein 1 in desmosome

Clinical findings

• Progression in stages
  • Spontaneous onset of painful flaccid, intraepidermal blisters
  • Lesions rupture and become confluent → erosions and crusts → re-epithelialization with hyperpigmentation but without scarring
• Pruritus is typically absent.
• Lesions typically first present on the oral mucosa (> 50% of cases), then on body parts exposed to pressure (e.g., intertriginous areas)

Diagnostics

• Autoantibodies against
  • Desmoglein 3 and desmoglein 1
• Tzanck test, Nikolsky sign: positive
• Histology and immunohistochemistry
  • Intraepidermal vesicle formation just above the basal layer of the epidermis
  • Acantholysis on biopsy: loss of intercellular connections between keratinocytes (“row of tombstones” appearance)
  • Deposition of IgG in the intercellular spaces of the epidermis (esp. early lesions)
  • Immunofluorescence: deposition of IgG in a reticular pattern around epidermal cells

Prognosis

• Often fatal without treatment!
  • Caused primarily by infections, fluid loss, and electrolyte disturbances
    • Fragile blisters rupture easily

Epidermolysis bullosa

---

• Definition: a genetic condition that causes the skin to become very fragile and blister easily in response to minor injury or friction
• Epidemiology: EBS is the most common type of EB.
• Etiology
  • Autosomal dominant inheritance
  • Mutations in keratin genes (e.g., KRT5, KRT14)
• Pathophysiology: mutations in keratin proteins → defective assembly of keratin filaments → disruption of the basal layer of keratinocytes → ↑ fragility of epithelial tissue
• Clinical features
  • Mainly limited to the palms and soles
  • Generally heal without scarring