with topical antibacterial agents such as mupirocin used for infected lesions. The use of dapsone or sulfapyridine is successful in most cases, and noticeable response to treatment may be seen within several days [61–64,77]. Treated disease lasting longer than a few weeks may benefit from adjunct therapy including prednisone, dicloxacillin, sulfamethoxypyridazine, and colchicine [77,78]. As in MMP, treatment of refractory cases with IVIG has shown e cacy [79–81]. Treatment of drug-induced LAD should begin with removal of the presumed causative agent. In cases of LAD induced by vancomycin, new lesions stop forming within approximately 2 weeks of cessation [67,68,82]. In persistent cases of drug-induced LAD, a short oral steroid course may be beneficial [60,61].

Epidermolysis bullosa acquisita

Clinical features

EBA is an autoimmune blistering disease of the skin and mucous membranes that is mediated by IgG autoantibodies against type VII collagen [83]. A small subset of EBA, however, is known to be due to IgA rather than to IgG [84]. Type VII collagen is a major component of the anchoring fibrils in the lamina densa of the epithelial basement membrane. There are three di erent phenotypes of this disease: mechanobullous, inflammatory, and cicatricial pemphigoid. The disease is rare, with an estimated annual incidence of 0.25 per 1 million in Western Europe [85]. The male-to-female ratio is 1:1.4, and it has been noted that patients of Korean descent have a higher predilection for EBA [86]. HLA-DR2 depicts hyperimmunity that is seen in EBA and in bullous forms of pemphigoid, pointing to an autoimmune etiology for these entities. Immunogenetic studies on EBA reveal that most black patients from the southeastern part of the United States have an association with HLA-DR2. Subsequent studies on a larger population of white patients failed to reveal any statistically significant HLA allele associations with EBA [87].

EBA typically presents in the third to fifth decade, with patients exhibiting various aspects of chronic conjunctivitis, symblepharon formation, keratitis, subepithelial corneal vesiculation, perforation, and possibly opacification. EBA presents with scarring blisters and milia at sites of trauma, such as elbows, knees, and buttocks and the dorsa of the hands and feet. The scarring nature of EBA can lead to nail destruction and hair loss [85,88]. EBA is most commonly nonor mildly inflammatory, manifested as tense vesicles and bullae. The blisters may be hemorrhagic and rupture easily, with subsequent erosion [89]. Other subsets of patients may also have mucosal involvement that can mimic MMP or can present with inflammatory blisters that mimic bullous pemphigoid. The blisters of patients who have the classic mechanobullous noninflammatory EBA resemble those in adult or child dystrophic epidermolysis bullosa because both disease

processes involve type VII collagen [90]. These lesions can also mimic bullous lupus erythematosus and porphyria cutanea tarda in the elderly, whereas the inflammatory form of EBA can resemble bullous pemphigoid because these blisters are tense and widespread [91].

Despite frequent mucous membrane involvement in EBA, this is usually limited to oral mucosa, and is then termed the cicatricial pemphigoid form of EBA [89]. EBA can also involve the nasal, pharyngeal, ocular, and esophageal mucosa or, in children, the oral mucosa, genitals, and ocular mucosa, causing symblepharon formation. In very severe cases (most notably cases mediated by IgA), total blindness has been reported [92,93].

Diagnostic studies

Various tests are used to diagnose EBA, including direct and indirect immunofluorescence, fluorescent overlay antigen mapping, immunoelectron microscopy, Western immunoblotting, and enzyme-linked immunosorbent assay (ELISA) [94]. Laboratory tests including urine porphyrin levels and antinuclear antibody are used to exclude porphyria cutanea tarda and to search for evidence of bullous systemic lupus erythematosus, which is also characterized by antibodies directed against type VII collagen. To diagnose EBA, histopathology from the edge of a new blister, direct immunofluorescence on normal-appearing perilesional skin, and indirect immunofluorescence with the patient’s serum on salt-split normal human skin substrate should be obtained [79]. The histopathology of EBA shows subepidermal blisters, with the epidermis remaining intact. In addition, there is a dermal infiltrate composed of monocytes and neutrophils, which is minimal in the classic form of EBA and more abundant in the inflammatory form [92]. Direct immunofluorescence reveals the immune-mediated disease process, with a thick band of IgG and, to a lesser extent, C3 deposited linearly at the BMZ [91]. Other immunoreactants such as IgM or IgA may also be seen. Indirect immunofluorescence demonstrates the presence of IgG antibodies directed toward type VII collagen and is used to di erentiate EBA from bullous pemphigoid [95]. The IgG autoantibodies in patients who have bullous pemphigoid bind to the epidermal roof of salt-split skin, whereas the dermal floor pattern of indirect immunofluorescence on salt-split skin substrate is also found in sera of patients who have bullous systemic lupus erythematosus and antiepiligrin cicatricial pemphigoid [94]. In immunoblotting, circulating autoantibodies bind a dermal protein of 290 kDa identified as type VII collagen, whereas detection of anti-type VII collagen antibodies by ELISA uses fusion proteins corresponding to di erent portions of the noncollagenous domain of type VII collagen [96].

Although the precise role of autoantibodies against type VII collagen is unknown, it has been hypothesized that they disrupt the assembly of type VII collagen into anchoring fibrils and interfere with their interactions with other extracellular matrix molecules [97]. Lesional skin histology initially reveals