| 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) |