Autoimmune blistering diseases

Blistering diseases differential diagnostics

Feature	Pemphigus Vulgaris (PV)	Bullous Pemphigoid (BP)	Dermatitis Herpetiformis (DH)	Epidermolysis Bullosa (EB)	Bullous Impetigo
Pathophysiology	Autoimmune (IgG) vs. Desmoglein 1 & 3 (Desmosomes)	Autoimmune (IgG) vs. Hemidesmosomes (BP180, BP230)	Autoimmune (IgA) deposition at dermal papillae	Genetic defect in adhesion proteins (e.g., Keratin, Collagen)	Bacterial toxin from S. aureus cleaves Desmoglein 1
Epidermal Split	Intraepidermal (Acantholysis)	Subepidermal	Subepidermal	Varies by type (intra- or subepidermal)	Intraepidermal (Stratum granulosum)
Clinical Presentation	Flaccid, easily ruptured bullae; erosions. Skin + oral mucosa.	Tense, firm bullae on erythematous/urticarial base. Intense pruritus.	Extremely pruritic vesicles on extensor surfaces (elbows, knees).	Blisters/erosions with minor trauma. Onset in infancy/childhood.	Flaccid bullae that rupture, leaving thin, varnish-like crust.
Nikolsky Sign	Positive	Negative	Negative	Positive	Positive
Immunofluorescence	Net-like (“chicken wire”) IgG pattern in epidermis	Linear IgG & C3 at dermoepidermal junction	Granular IgA deposits at dermal papillae tips	Not used for autoantibodies; used to ID missing protein	Not applicable
Histology	Acantholytic cells (Tzank cells); suprabasal split	Eosinophilic infiltrate; non-acantholytic split below epidermis.	Neutrophilic microabscesses at dermal papillae tips	Depends on specific gene defect	Cleavage within stratum granulosum; few inflammatory cells
Key Association	Other autoimmune diseases, drug-induced (penicillamine)	Elderly population (>60 years)	Celiac Disease (strong!)	Familial inheritance	Typically affects children
Treatment	Corticosteroids, Rituximab	Topical/systemic corticosteroids	Dapsone, gluten-free diet	Supportive care, wound management	Antibiotics (e.g., Mupirocin, Cephalexin)

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Bullous pemphigoid

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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

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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

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• 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