Inflammatory, Autoimmune and Connective Tissue Diseases
Autoimmune blistering
Pemphigus vulgaris (intraepidermal, flaccid blisters, mucosal, anti-Dsg3), pemphigus foliaceus (superficial, anti-Dsg1), bullous pemphigoid (subepidermal, tense blisters, anti-BP180/230), dermatitis herpetiformis (celiac, IgA at dermal papillae), and epidermolysis bullosa acquisita (type VII collagen). Direct immunofluorescence pattern is the discriminator: intercellular IgG (pemphigus) vs linear IgG/C3 at basement membrane (pemphigoid).
Connective tissue disease
Lupus (malar rash, photosensitivity, ANA, anti-dsDNA, anti-Sm), dermatomyositis (Gottron papules, heliotrope, anti-Mi-2, malignancy screening), systemic sclerosis (sclerodactyly, anti-centromere in limited, anti-Scl-70 in diffuse), and Sjögren syndrome.
Vasculitis and neutrophilic dermatoses
Leukocytoclastic vasculitis (palpable purpura, immune complexes), Sweet syndrome (fever, neutrophilia, tender plaques), and pyoderma gangrenosum (associated with IBD, myeloma).
Traps
- Equating mucosal involvement only with PV; drug-induced pemphigus also occurs.
- Missing malignancy workup in adult dermatomyositis.
- Confusing Sweet syndrome with infection; biopsy shows neutrophilic dermal infiltrate without organisms.
Rule of thumb
For blistering disease, the level of split plus DIF pattern narrows the diagnosis to one or two entities.
Worked example
An elderly patient with tense bullae and negative Nikolsky: DIF shows linear IgG/C3 at the BMZ; diagnose bullous pemphigoid and treat with topical/systemic steroids.