Chapter 055. Immunologically Mediated Skin Diseases (Part 3)

Pemphigus Foliaceus Pemphigus foliaceus (PF) is distinguished from PV by several features. In PF, acantholytic blisters are located high within the epidermis, usually just beneath the stratum corneum. Hence PF is a more superficial blistering disease than PV. The distribution of lesions in the two disorders is much the same, except that in PF mucous membranes are almost always spared. Patients with PF rarely demonstrate intact blisters but rather exhibit shallow erosions associated with erythema, scale, and crust formation. Mild cases of PF resemble severe seborrheic dermatitis; severe PF may cause extensive exfoliation. Sun exposure (ultraviolet irradiation) may be...
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Chapter 055. Immunologically Mediated Skin Diseases (Part 3) Chapter 055. Immunologically Mediated Skin Diseases (Part 3) Pemphigus Foliaceus Pemphigus foliaceus (PF) is distinguished from PV by several features. InPF, acantholytic blisters are located high within the epidermis, usually just beneaththe stratum corneum. Hence PF is a more superficial blistering disease than PV.The distribution of lesions in the two disorders is much the same, except that in PFmucous membranes are almost always spared. Patients with PF rarely demonstrateintact blisters but rather exhibit shallow erosions associated with erythema, scale,and crust formation. Mild cases of PF resemble severe seborrheic dermatitis;severe PF may cause extensive exfoliation. Sun exposure (ultraviolet irradiation)may be an aggravating factor. Fogo selvagem (FS), an endemic form of PFthought to develop as a consequence of environmental stimuli (e.g., insect bites),is found in south central rural Brazil as well as selected sites in Latin America andTunisia. Patients with PF have immunopathologic features in common with PV.Specifically, direct immunofluorescence microscopy of perilesional skindemonstrates IgG on the surface of keratinocytes. Similarly, patients with PF havecirculating IgG autoantibodies directed against the surface of keratinocytes.Guinea pig esophagus is the optimal substrate for indirect immunofluorescencemicroscopy studies of sera from patients with PF. In PF, autoantibodies aredirected against Dsg1, a 160-kDa desmosomal cadherin. As noted for PV, theautoantibody profile in patients with PF (i.e., anti-Dsg1 IgG) and the tissuedistribution of this autoantigen (i.e., expression in oral mucosa that is compensatedby coexpression of Dsg3) is thought to account for the distribution of lesions inthis disease. Although pemphigus has been associated with several autoimmunediseases, its association with thymoma and/or myasthenia gravis is particularlynotable. To date, >30 cases of thymoma and/or myasthenia gravis have beenreported in association with pemphigus, usually with PF. Patients may alsodevelop pemphigus as a consequence of drug exposure; drug-induced pemphigususually resembles PF rather than PV. Drugs containing a thiol group in theirchemical structure (e.g., penicillamine, captopril, enalapril) are most commonlyassociated with drug-induced pemphigus. Nonthiol drugs linked to pemphigusinclude penicillins, cephalosporins, and piroxicam. It has been suggested thatthiol- and nonthiol-containing drugs induce pemphigus via biochemical andimmunologic mechanisms, respectively. Hence, the better prognosis upon drugwithdrawal in cases of pemphigus induced by thiol-containing medications. Somecases of drug-induced pemphigus are durable and require treatment with systemicglucocorticoids and/or immunosuppressive agents. PF is generally a less severe disease than PV and carries a better prognosis.Localized disease can sometimes be treated with topical or intralesionalglucocorticoids; more active cases can usually be controlled with systemicglucocorticoids. Patients with severe, treatment-resistant disease may require moreaggressive interventions as described above for patients with severe PV. Paraneoplastic Pemphigus Paraneoplastic pemphigus (PNP) is an autoimmune acantholyticmucocutaneous disease associated with an occult or confirmed neoplasm. Patientswith PNP typically show painful mucosal erosive lesions in association withpapulosquamous and/or lichenoid eruptions that often progress to blisters. Palmand sole involvement is common in these patients and raises the possibility thatprior reports of neoplasia-associated erythema multiforme actually may haverepresented unrecognized cases of PNP. Biopsies of lesional skin from thesepatients show varying combinations of acantholysis, keratinocyte necrosis, andvacuolar-interface dermatitis. Direct immunofluorescence microscopy of patientskin shows deposits of IgG and complement on the surface of keratinocytes and(variably) similar immunoreactants in the epidermal basement membrane zone.Patients with PNP have IgG autoantibodies against cytoplasmic proteins that aremembers of the plakin family (e.g., desmoplakins I and II, bullous pemphigoidantigen 1, envoplakin, periplakin, and plectin) and cell-surface proteins that aremembers of the cadherin family (e.g., Dsg3 and Dsg1). Passive transfer studieshave shown that autoantibodies from patients with PNP are pathogenic. The predominant neoplasms associated with PNP are non-Hodgkinslymphoma, chronic lymphocytic leukemia, thymoma, spindle cell tumors,Waldenströms macroglobulinemia, and Castlemans disease; the latter isparticularly common among children with PNP. In ...