A number of immunologically mediated skin diseases and immunologically mediated systemic disorders with cutaneous manifestations are now recognized as distinct entities with consistent clinical, histologic, and immunopathologic findings. Clinically, these disorders are characterized by morbidity (pain, pruritus, disfigurement) and, in some instances, result in death (largely due to loss of epidermal barrier function and/or secondary infection). The major features of the more common immunologically mediated skin diseases are summarized in this chapter (Table 73-1), as are the autoimmune systemic disorders with cutaneous manifestations.
AUTOIMMUNE CUTANEOUS DISEASES
Pemphigus refers to a group of autoantibody-mediated intraepidermal blistering diseases characterized by loss of cohesion between epidermal cells (a process termed acantholysis). Manual pressure to the skin of these patients may elicit the separation of the epidermis (Nikolsky’s sign). This finding, while characteristic of pemphigus, is not specific to this group of disorders and is also seen in toxic epidermal necrolysis, Stevens-Johnson syndrome, and a few other skin diseases.
Pemphigus vulgaris (PV) is a mucocutaneous blistering disease that predominantly occurs in patients >40 years of age. PV typically begins on mucosal surfaces and often progresses to involve the skin. This disease is characterized by fragile, flaccid blisters that rupture to produce extensive denudation of mucous membranes and skin (Fig. 73-1). The mouth, scalp, face, neck, axilla, groin, and trunk are typically involved. PV may be associated with severe skin pain; some patients experience pruritus as well. Lesions usually heal without scarring except at sites complicated by secondary infection or mechanically induced dermal wounds. Postinflammatory hyperpigmentation is usually present for some time at sites of healed lesions.
Pemphigus vulgaris. A. Flaccid bullae are easily ruptured, resulting in multiple erosions and crusted plaques. B. Involvement of the oral mucosa, which is almost invariable, may present with erosions on the gingiva, buccal mucosa, palate, posterior pharynx, or tongue. (B, Courtesy of Robert Swerlick, MD; with permission.)
TABLE 73-1Immunologically Mediated Blistering Diseases |Favorite Table|Download (.pdf) TABLE 73-1Immunologically Mediated Blistering Diseases
|Disease ||Clinical Manifestations ||Histology ||Immunopathology ||Autoantigensa |
|Pemphigus vulgaris ||Flaccid blisters, denuded skin, oromucosal lesions ||Acantholytic blister formed in suprabasal layer of epidermis ||Cell surface deposits of IgG on keratinocytes ||Dsg3 (plus Dsg1 in patients with skin involvement) |
|Pemphigus foliaceus ||Crusts and shallow erosions on scalp, central face, upper chest, and back ||Acantholytic blister formed in superficial layer of epidermis ||Cell surface deposits of IgG on keratinocytes ||Dsg1 |
|Paraneoplastic pemphigus ||Painful stomatitis with papulosquamous or lichenoid eruptions that may progress to blisters ||Acantholysis, keratinocyte necrosis, and vacuolar interface dermatitis ||Cell surface deposits of IgG and C3 on keratinocytes and (variably) similar immunoreactants in epidermal BMZ ||Plakin protein family members ...|