Autoimmune, Connective Tissue and Blistering Diseases
Domain 6 tests autoantibody patterns and the cleavage level that explains blister mechanics.
Intraepidermal blistering
- Pemphigus vulgaris: flaccid bullae, oral erosions, positive Nikolsky sign; IgG against desmoglein 3 (mucosa) and desmoglein 1 (skin); direct immunofluorescence shows intercellular chicken-wire IgG.
- Pemphigus foliaceus: superficial crusted lesions, desmoglein 1 only, no mucosal disease.
Subepidermal blistering
- Bullous pemphigoid: tense bullae in the elderly, eosinophils, linear IgG/C3 at the basement membrane; BP180 and BP230 antibodies.
- Dermatitis herpetiformis: grouped vesicles on elbows and knees, granular IgA in dermal papillae, celiac disease; dapsone and gluten-free diet.
- Linear IgA disease, epidermolysis bullosa acquisita (collagen VII, u-serrated pattern), cicatricial pemphigoid.
Connective tissue disease
- Lupus: acute malar rash, subacute annular/papulosquamous lesions with anti-Ro, discoid scarring; lupus band alone is not diagnostic.
- Dermatomyositis: heliotrope, Gottron papules, anti-Mi-2; anti-TIF1-gamma signals malignancy, so screen for cancer.
- Systemic sclerosis: anti-centromere in limited/CREST, anti-Scl-70 in diffuse disease; morphea is localized.
Worked example
A 74-year-old has tense pruritic bullae on trunk and limbs with oral sparing. Direct immunofluorescence shows linear IgG and C3 along the basement membrane; ELISA is positive for BP180. Diagnosis: bullous pemphigoid. Reasoning: tense blisters and eosinophils favour pemphigoid; linear IgG at the basement membrane excludes pemphigus.
Traps
Nikolsky can be positive in pemphigoid and does not equal pemphigus. Mucosal-dominant pemphigus may have only anti-desmoglein 3. Do not diagnose systemic lupus from a lupus band alone.