Low sensitivity of type VII collagen enzyme‐linked immunosorbent assay in epidermolysis bullosa acquisita: serration pattern analysis on skin biopsy is required for diagnosis

Summary Background The type VII collagen (coll VII) enzyme‐linked immunosorbent assay (ELISA) has been reported to have high sensitivity (> 93%) and specificity (> 96%) for diagnosing epidermolysis bullosa acquisita (EBA) in patients who are seropositive on indirect immunofluorescence on salt‐split skin (SSS). Objectives To investigate the added value of the coll VII ELISA in the laboratory diagnosis of SSS‐positive and SSS‐negative EBA and to correlate the ELISA index with disease episode. Methods The coll VII ELISA was performed on banked sera of 28 patients with EBA: 15 SSS positive and 13 SSS negative. Sera from healthy blood donors (n = 17) and patients with other autoimmune blistering diseases (n = 29) served as controls. In four patients, the ELISA index was measured longitudinally. Serration pattern analysis by direct immunofluorescence has been prospectively performed since 2000 in 19 patients. Results The sensitivity in the SSS‐positive group was 80% whereas it was 23% in the SSS‐negative group. In the prospective EBA subset it was 45%. The sensitivity of u‐serration pattern analysis on skin biopsy was 89%. Ten (53%) of these cases were seronegative with both ELISA and SSS, and would have been missed by serum analysis alone. Of the 46 control sera, one serum tested positive (specificity 97·8%). The coll VII ELISA correlated with disease activity over time in individual patients. Conclusions The coll VII ELISA has limited added value in SSS‐negative EBA cases. The ELISA test is valuable in differentiating EBA from antilaminin‐332 mucous membrane pemphigoid and anti‐p200 pemphigoid and in its ability to monitor patients with EBA serologically. U‐serration pattern analysis on immunofluorescence skin biopsy is the gold standard for the diagnosis of EBA. What's already known about this topic? The type VII collagen (coll VII) enzyme‐linked immunosorbent assay (ELISA) has been described as a highly sensitive and specific assay for patients with epidermolysis bullosa acquisita (EBA) who were preselected by positive indirect immunofluorescence microscopy on salt‐split skin (SSS). Serration pattern analysis is a nonserological alternative for making the laboratory diagnosis. What does this study add? We determined the performance of the coll VII ELISA in SSS‐positive and SSS‐negative patients with EBA and found a sensitivity of 80% and 23%, respectively. In all 10 cases (36%) that remained seronegative by either ELISA or SSS, confirmation of the diagnosis