Chapter 16 Immunologic skin diseases

Abstract

Several immunologic skin disorders are of known importance to the clinical immunologist. Pemphigus vulgaris (PV) is a chronic bullous disease having flaccid vesicles and bullae with ulcerations that is associated with low mortality (5% to 10%). Pemphigus foliaceus (PF) has more superficial blisters rarely associated with slow desquamating ulcerating lesions. A subcategory, fogo selvagem (FS), is spread by an arthropod vector and is endemic to Brazil. Antigens to PV, PF, and FS are all unique. Bullous pemphigoid (BP) can present with tense bullae on the abdomen, groin, and flexural aspects of the extremities with rare mucous membrane involvement; these patients are usually elderly (>60 years). Remission occurs with therapy in most cases and no correlation is noted with antibody titers or immunofluorescent (IF) studies and severity of the disease. Brunsting-Perry pemphigoid is a very mild form of BP. Dermatitis herpetiformis (DH) has intensely pruritic lesions and symmetric vesicles located primarily on extensor surfaces, interscapular areas, and sacral areas, with subepidermal vesicles and adjacent abscesses in dermal papillae. DH is often associated with an HLA-B8/DRW3(DQ) haplotype and asymptomatic bowel disease, especially gluten-sensitive enteropathy. Chronic bullous dermatosis of childhood (CBD-CH) is a rare vesiculobullous disease of young children, with tense bullae in intertriginous and flexural areas causing extensive skin involvement and denudation with minimal symptoms. Epidermolysis bullosa aquisita (EBA) is clinically similar to BP and porphyria cutanea tarda, with lesions over the hands, feet, ears, and elbows induced by trauma. No therapy is known to be effective. Herpes gestationalis (HG) is a vesicular, bullous eruption of pregnancy occurring in approximately 1 / 10.000 to l/50,000 white births. The illness may recur, with an earlier onset with each subsequent pregnancy. Lesions are pruritic, urticarial (containing lymphocytes, histiocytes, and eosinophils), and bullous. Offspring may develop the disease. localization of the lesions, all of which contain imrnunoglobulin depositions, is important in distinguishing between them. lntraepidermal lesions are associated with PV, PF, and FS. Those exhibiting dermoepidermal junctional deposition include BP, DH, and CBD-CH. Subepidermal deposition (dermal side) is seen in EBA and HG. Antibodies to tissue components are noted in PV (antiepithelial antibodies) and PF. In the latter, antibody levels are not a useful guide to regulate therapy or as to prognosis. Autoimmune diseases are reported in association with PV (systemic lupus erythematosus and myasthenia gravis), PF (Senear-Usher syndrome), and EBA. Causative factors are not known, although drugs have been associated with PV (phenylbutazone, penicillamine, and rifampin) and BP. In DH, antireticulin, antithyroglobulin, and antimicrosomal and antinuclear antibodies are found. As noted, the vesiculobullous diseases primarily involve the skin, with the exception of cicatricial pemphigoid (CP), a clinical variation of BP that has primarily mucous membrane involvement. CP is not benign, as scarring of the oral cavity and conjunctival sac may occur. The immunopathology is the same in CP and BP. EBA may also have both skin and mucous membrane involvement. The pathophysiology of the vesiculobullous diseases consists of the deposition of immunoglobulins and complement in the skin. DH is associated primarily with activation of the alternate complement pathway. In CBD-CH, positive IF is associated with clearance of the clinical syndrome and indirect IF results are negative. In HG, HG factor is an IgG that deposits on the basement membrane zone (BMZ) fixing complement and giving positive indirect IF studies. The primary type of immunoglobulin involved in complement activation is important. IgG is associated with PV, PF, and BP; IgA is associated with PF, BP, DH (granular deposition), and CBD-CH (linear deposition), whereas IgM is also seen in PF and BP. Multiple immunoglobulins are involved in some. Therapy for all except EBA involves either systemic or topical steroids. No consistently effective therapy has been found for EBA. In HG, sulfones are used in early pregnancy, whereas systemic steroids and antihistamines are used in late pregnancy. In PV, immunosuppressants, such as azothiazine. methotrexate,