Chapter 055. Immunologically Mediated Skin Diseases (Part 2)

Pemphigus Vulgaris 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 (Nikolskys 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 predominates in patients 40 years. PV typically begins on mucosal surfaces; itoften progresses to a mucocutaneous disease in which fragile,...
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Chapter 055. Immunologically Mediated Skin Diseases (Part 2) Chapter 055. Immunologically Mediated Skin Diseases (Part 2) Pemphigus Vulgaris Pemphigus refers to a group of autoantibody-mediated intraepidermalblistering diseases characterized by loss of cohesion between epidermal cells (aprocess termed acantholysis). Manual pressure to the skin of these patients mayelicit the separation of the epidermis (Nikolskys sign). This finding, whilecharacteristic of pemphigus, is not specific to this group of disorders and is alsoseen in toxic epidermal necrolysis, Stevens-Johnson syndrome, and a few otherskin diseases. Pemphigus vulgaris (PV) is a mucocutaneous blistering disease thatpredominates in patients >40 years. PV typically begins on mucosal surfaces; itoften progresses to a mucocutaneous disease in which fragile, flaccid blistersrupture to produce extensive denudation of the skin (Fig. 55-1). PV typicallyinvolves the mouth, scalp, face, neck, axilla, groin, and trunk. PV may beassociated with severe skin pain; some patients experience pruritus as well.Lesions usually heal without scarring, except at sites complicated by secondaryinfection or mechanically induced dermal wounds. Postinflammatoryhyperpigmentation is usually present at sites of healed lesions for some time. Figure 55-1 Pemphigus vulgaris. A. Pemphigus vulgaris demonstrating flaccid bullaethat are easily ruptured, resulting in multiple erosions and crusted plaques. B.Pemphigus vulgaris almost invariably involves the oral mucosa and may presentwith erosions involving the gingiva, buccal mucosa, palate, posterior pharynx, orthe tongue. (B, Courtesy of Robert Swerlick, MD.) Biopsies of early lesions demonstrate intraepidermal vesicle formationsecondary to loss of cohesion between epidermal cells (i.e., acantholytic blisters).Blister cavities contain acantholytic epidermal cells, which appear as roundhomogeneous cells containing hyperchromatic nuclei. Basal keratinocytes remainattached to the epidermal basement membrane, hence blister formation is withinthe suprabasal portion of the epidermis. Lesional skin may contain focalcollections of intraepidermal eosinophils within blister cavities; dermal alterationsare slight, often limited to an eosinophil-predominant leukocytic infiltrate. Directimmunofluorescence microscopy of lesional or intact patient skin shows depositsof IgG on the surface of keratinocytes; deposits of complement components aretypically found in lesional but not uninvolved skin. Deposits of IgG onkeratinocytes are derived from circulating autoantibodies directed against cell-surface autoantigens. Such circulating autoantibodies can be demonstrated in 80–90% of PV patients by indirect immunofluorescence microscopy; monkeyesophagus is the optimal substrate for these studies. Patients with PV have IgGautoantibodies directed against desmogleins (Dsgs), transmembrane desmosomalglycoproteins that belong to the cadherin family of calcium-dependent adhesionmolecules. Such autoantibodies can be precisely quantitated by enzyme-linkedimmunosorbent assay (ELISA). Patients with early PV (i.e., mucosal disease) haveonly IgG autoantibodies directed against Dsg3; patients with advanced PV (i.e.,mucocutaneous disease) have IgG autoantibodies directed against both Dsg3 andDsg1. Experimental studies have shown that autoantibodies from patients with PVare pathogenic (i.e., responsible for blister formation) and that their titer correlateswith disease activity. Recent studies have shown that the anti-Dsg autoantibodyprofile in these patients sera as well as the tissue distribution of Dsg3 and Dsg1determine the site of blister formation in patients with pemphigus. Coexpression ofDsg3 and Dsg1 by epidermal cells protects against pathogenic IgG directedagainst either cadherin but not pathogenic autoantibodies directed against both. PV can be life-threatening. Prior to the availability of glucocorticoids, themortality ranged from 60–90%; the current mortality is ~5%. Common causes ofmorbidity and mortality are infection and complications of treatment withglucocorticoids. Bad prognostic factors include advanced age, widespreadinvolvement, and the requirement for high doses of glucocorticoids (with orwithout other immunosuppressive agents) for control of disease. The course of PVin individual patients is variable and difficult to predict. Some patients achieveremission, while others may require long-term treatment or succumb tocomplications of their disease or its treatment. The mainstay of treatment issystemic glucocorticoids. Patients with moderate to severe PV are usually startedon prednisone, 1 mg/kg per day. If new lesions continue to appear after 1–2 weeksof treatme ...