Blistering diseases

Pemphigus foliaceus

Pemphigus foliaceus is a subcorneal vesiculobullous disorder caused by autoantibodies directed at an intercellular keratinocyte adhesion protein: desmoglein 1 (160 kD). The disease usually presents with superficial crusted erosions upon the face and upper trunk. The superficial nature of the blisters makes them fragile, and upon presentation most patients lack intact bullae.

The presence of a subcorneal blister, with acantholytic cells and scattered eosinophils, is highly suggestive of pemphigus foliaceus. Direct immunofluorescence (DIF) is diagnostic and demonstrates intercellular IgG and C3 deposition, primarily confined to the upper half of the epidermis. The split occurs in the granular layer, as in staphylococcal scalded-skin syndrome. Pemphigus foliaceus may demonstrate neutrophils within the vesicle, making distinction from bullous impetigo difficult. A tissue Gram stain may be helpful, but the presence of an impetiginized crust does not wholly exclude pemphigus foliaceus.

Pemphigus erythematosus blends the immunohistologic findings of pemphigus foliaceus with those of lupus erythematosus. Patients often have a positive serum antinuclear antibody (ANA). Immunofluorescence studies demonstrate intercellular deposition of immunoreactants and a “lupus band” of granular immunoreactants at the dermoepidermal junction.

Subcorneal pustular dermatosis (Sneddon–Wilkinson disease)

Cases of subcorneal pustular dermatosis with intercellular deposition of IgA have been reclassified as IgA pemphigus. Subcorneal pustular dermatosis may represent a subclass of pustular psoriasis, although mitotic figures within the underlying epidermis, common to psoriasis, are not identified in subcorneal pustular dermatosis. The classic patient is an older woman with annular or polycyclic lesions of the trunk or groin with pustules at the periphery.

Acute generalized exanthematous pustulosis

Acute generalized exanthematous pustulosis (AGEP) is an uncommon reaction to exogenous medications. Beta-lactam antibiotics and macrolides are most often implicated, but a myriad of other drug associations have been reported. The presence of eosinophils in the inflammatory infiltrate helps distinguish the condition from pustular psoriasis. Early pustules may be associated with hair follicles or sweat ducts.

Pemphigus vulgaris

Pemphigus vulgaris is an intraepidermal vesiculobullous disorder caused by autoantibodies directed at an intercellular keratinocyte adhesion protein: desmoglein 3 (130 kD). The disease presents with erosions of the skin and mucosa. Often the disease begins in the posterior oropharynx weeks before cutaneous lesions are noted. Most patients lack intact bullae upon presentation. Erythematous skin shears easily when lateral pressure is applied (Nikolsky sign).

Clefting above the basal layer, with acantholysis of the remaining basilar keratinocytes, leads to a visual impression likened to “rows of tombstones” sitting upon the dermal papillae. Tracking of the blistering down adnexal structures is often demonstrated. Direct immunofluorescence is diagnostic and demonstrates intercellular IgG and C3 deposition in a “netlike” pattern, primarily confined to the lower half of the epidermis. Pemphigus antibodies can also be measured via enzyme-linked immunosorbent assay (ELISA)–based technology and generally titer to disease activity. DIF studies on plucked hairs have also been recently suggested to monitor for remission/recurrences.

Pemphigus vegetans is a related disorder that demonstrates vegetative cutaneous lesions with epidermal hyperplasia and lesser vesiculation. Suprabasilar crypts of eosinophils may be identified within the acanthotic epidermis.

Familial benign chronic pemphigus (Hailey–Hailey disease)

Hailey–Hailey disease is an autosomal-dominant, inherited disease caused by mutations in the ATP2C1 gene. This gene encodes for a portion of a calcium pump essential for proper keratinocyte differentiation and adhesion. Skin of the intertriginous areas is most often affected, and the appearance has been likened to “wet tissue paper.” Acantholysis at all levels of the epidermis yields the histologic appearance of a “dilapidated brick wall.” Although the disease itself is not immunologically mediated, superinfection of macerated skin by bacteria or yeast may engender an inflammatory infiltrate in the superficial dermis.