• Immunobullous disease due to circulating autoantibodies that bind two components of hemidesmosomes, i.e. structures that provide adhesion between the epidermis and the dermis; the two antigens are collagen XVII (also referred to BP antigen 2 [BPA2] or BP180) and BPA1/BP230.

• Occurs more commonly in the elderly and can be drug-induced (e.g. furosemide); rarely, lesions are induced by ultraviolet light or radiation therapy.

• Both pruritic fixed urticarial plaques and tense bullae are seen (Figs. 24.1 and 24.2); the latter can develop within normal skin or areas of erythematous skin and produce erosions when they rupture; oral lesions are much less common than in pemphigus vulgaris (10–30% of patients).

• Pruritus and nonspecific eczematous (see Fig. 24.1D) or papular lesions can precede the more characteristic cutaneous lesions and may be the predominant finding; unusual variants include dyshidrosiform (palms and soles), vegetans (major body folds), and localized (e.g. pretibial in adults; vulvar in children, acral in infants), as well as those that mimic prurigo nodularis and toxic epidermal necrolysis (Fig. 24.3).

• Histologically, a subepidermal bulla plus an infiltrate of eosinophils is seen when the lesions are bullous; DIF demonstrates immunodeposits of IgG and/or C3 in a linear array along the basement membrane zone (see Fig. 23.3B); in general, by salt-split skin immunofluorescence studies, the immunodeposits are in the roof (epidermal side) of the blister (Fig. 24.4).

• Both enzyme-linked immunosorbant assay and IIF can detect circulating autoantibodies in the sera in at least 70–80% of patients (see Table 23.1).

• At least 50% of patients have a peripheral eosinophilia.

• DDx: linear IgA bullous dermatosis (LABD), epidermolysis bullosa acquisita (EBA), mucous membrane pemphigoid, various forms of pemphigus, hypersensitivity reactions (including to drugs), primary pruritus, allergic contact dermatitis, scabies, urticaria (but individual lesions transient).

• Rx: see Table 24.1.

• Chronic immunobullous disease due to autoantibodies that bind several components of the BMZ of the skin and mucosae, most often BP180 and laminin 332 (laminin 5); although heterogenous in its presentation, a tendency to scarring is typically seen.

• The mucous membranes represent the major site of involvement, in particular conjunctival (erosions, scarring with symblepharon formation, blindness) and oral mucosae (persistent erosions of the buccal and palatal mucosae, desquamative gingivitis) (Figs. 24.5 and 24.6).

• Additional sites of involvement are the nasopharynx, larynx, and esophagus; a few authors have suggested that patients with anti-laminin 332 immunodeposits have an increased risk of internal malignancy.

• Cutaneous lesions are seen in a quarter of patients and favor the head and neck region and upper trunk; erythematous plaques that develop vesicles, erosions, and scarring are characteristic (Fig. 24.7).

• Histologic and DIF features are similar to BP, but there is usually a sparser infiltrate and less eosinophils but fibrosis may be present; DIF positivity (IgG and/or C3 >> IgA) is greater for mucosa (50–90%) than for skin; circulating autoantibodies are detected by IIF in a minority of patients (20–30%).

• DDx: pemphigus vulgaris, occasionally BP, EBA, and LABD; if limited to oral mucosa, lichen planus or pemphigus vulgaris (see Fig. 59.5); if limited to scalp, consider other causes of scarring alopecia.

• Rx: potent topical or intralesional CS, dapsone, cyclophosphamide (severe or progressive ocular disease), alone or in combination with systemic CS, and rituximab.

• Autoimmune bullous disease due to autoantibodies that bind to collagen VII; the latter forms anchoring fibrils within the upper dermis and they play an important role in adhesion of the epidermis to the dermis.

• Two major clinical forms: (1) mechanobullous which resembles the genetic disorder epidermolysis bullosa; and (2) inflammatory which resembles bullous pemphigoid (Fig. 24.8).

• In the more common mechanobullous form, bullae arise in sites of friction and are followed by erosions, scarring, and milia formation (Fig. 24.9); oral lesions can also be seen (Fig. 24.10).

• Associated systemic disorders include inflammatory bowel disease, in particular Crohn’s disease, and plasma cell dyscrasias.

• Histological and DIF features are similar to BP, but there is usually a sparser infiltrate and few eosinophils in the mechanobullous form; DIF studies demonstrate linear IgG > C3 or IgA at the basement membrane zone; circulating autoantibodies are detected in ~50% of patients and by salt-split skin immunofluorescence studies, the immunodeposits are in the floor (dermal side) of the blister (see Fig. 24.4).

• DDx: inherited forms of epidermolysis bullosa, porphyria cutanea tarda (and other rare variants of porphyria), pseudoporphyria, bullous pemphigoid, LABD, mucous membrane pemphigoid, bullous systemic lupus erythematosus (also autoantibodies against collagen VII).

• Rx: difficult to treat; potent topical CS, oral CS, steroid-sparing agents (e.g. mycophenolate mofetil), dapsone, rituximab.