Chapter 055. Immunologically Mediated Skin Diseases (Part 6)

Linear IgA Disease Linear IgA disease, once considered a variant form of dermatitis herpetiformis, is actually a separate and distinct entity. Clinically, these patients may resemble individuals with DH, BP, or other subepidermal blistering diseases. Lesions typically consist of papulovesicles, bullae, and/or urticarial plaques predominantly on central or flexural sites. Oral mucosal involvement occurs in some patients. Severe pruritus resembles that seen in patients with DH. Patients with linear IgA disease do not have an increased frequency of the HLA-B8/DRw3 haplotype or an associated enteropathy and hence are not candidates for treatment with a gluten-free diet. ...
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Chapter 055. Immunologically Mediated Skin Diseases (Part 6) Chapter 055. Immunologically Mediated Skin Diseases (Part 6) Linear IgA Disease Linear IgA disease, once considered a variant form of dermatitisherpetiformis, is actually a separate and distinct entity. Clinically, these patientsmay resemble individuals with DH, BP, or other subepidermal blistering diseases.Lesions typically consist of papulovesicles, bullae, and/or urticarial plaquespredominantly on central or flexural sites. Oral mucosal involvement occurs insome patients. Severe pruritus resembles that seen in patients with DH. Patientswith linear IgA disease do not have an increased frequency of the HLA-B8/DRw3haplotype or an associated enteropathy and hence are not candidates for treatmentwith a gluten-free diet. The histologic alterations in early lesions may be virtually indistinguishablefrom those in DH. However, direct immunofluorescence microscopy of normal-appearing perilesional skin reveals linear deposits of IgA (and often C3) in theepidermal basement membrane zone. Most patients with linear IgA diseasedemonstrate circulating IgA anti-basement membrane autoantibodies directedagainst neoepitopes in the proteolytically processed extracellular domain ofBPAG2. These patients generally respond to treatment with dapsone, 50–200mg/d. Epidermolysis Bullosa Acquisita EBA is a rare, noninherited, polymorphic, chronic, subepidermal blisteringdisease. (The inherited form is discussed in Chap. 357.) Patients with classic ornoninflammatory EBA have blisters on noninflamed skin, atrophic scars, milia,nail dystrophy, and oral lesions. Because lesions generally occur at sites exposedto minor trauma, classic EBA is considered to be a mechanobullous disease. Otherpatients with EBA have widespread inflammatory, scarring, and bullous lesionsthat resemble severe BP. Inflammatory EBA may evolve into the classic,noninflammatory form of this disease. Rare patients present with lesions thatpredominate on mucous membranes. The HLA-DR2 haplotype is found withincreased frequency in EBA patients. Recent studies suggest that EBA is oftenassociated with inflammatory bowel disease (especially Crohns disease). The histology of lesional skin varies depending on the character of thelesion being studied. Noninflammatory bullae show subepidermal blisters with asparse leukocytic infiltrate and resemble those in patients with porphyria cutaneatarda. Inflammatory lesions consist of neutrophil-rich subepidermal blisters. EBApatients have continuous deposits of IgG (and frequently C3 as well as othercomplement components) in a linear pattern within the epidermal basementmembrane zone. Ultrastructurally, these immunoreactants are found in thesublamina densa region in association with anchoring fibrils. Approximately 50%of EBA patients have demonstrable circulating IgG anti-basement membraneautoantibodies directed against type VII collagen—the collagen species thatcomprises anchoring fibrils. Such IgG autoantibodies bind the dermal side of 1 MNaCl split skin (in contrast to IgG autoantibodies in patients with BP). Recentstudies have shown that passive transfer of experimental or patient IgG directedagainst type VII collagen can produce lesions in mice that clinically,histologically, and immunopathologically resemble those seen in patients withinflammatory EBA. Treatment of EBA is generally unsatisfactory. Some patients withinflammatory EBA may respond to systemic glucocorticoids, either alone or incombination with immunosuppressive agents. Other patients (especially those withneutrophil-rich inflammatory lesions) may respond to dapsone. The chronic,noninflammatory form of this disease is largely resistant to treatment, althoughsome patients may respond to cyclosporine, azathioprine, or IV immunoglobulin(IVIg). Cicatricial Pemphigoid Cicatricial pemphigoid (CP) is a rare, acquired, subepithelialimmunobullous disease characterized by erosive lesions of mucous membranesand skin that result in scarring of at least some sites of involvement. Common sitesof involvement include the oral mucosa (especially the gingiva) and conjunctiva;other sites that may be affected include the nasopharyngeal, laryngeal, esophageal,and anogenital mucosa. Skin lesions (present in about one-third of patients) tend topredominate on the scalp, face, and upper trunk and generally consist of a fewscattered erosions or tense blisters on an erythematous or urticarial base. CP istypically a chronic and progressive disorder. Serious complications may arise as aconsequence of ocular, laryngeal, esophageal, or anogenital lesions. Erosiveconjunctivitis may result in shortened fornices, symblephara, ankyloblepharon, ...