Diagnostic Agreement in Subepidermal Blistering Diseases: Is ELISA Test Reliable as Direct Immunofluorescence? A Systematic Review, Meta-Analysis, and Trial Sequential Analysis

Objectives: Direct immunofluorescence (DIF) is the gold standard for diagnosing subepidermal blistering diseases (SBDs). However, DIF requires specialized expertise; therefore, alternative immunological methods such as enzyme-linked immunosorbent assays (ELISA) are worth exploring. The aim of this review was to evaluate the diagnostic agreement between DIF and ELISA for the diagnosis of SBD. Materials and Methods: A systematic literature review of international journals and electronic databases (MEDLINE via OVID, Scopus, and Web of Science) was conducted between their inception and December 2023. The risk of bias and overall quality of evidence were assessed using the Newcastle-Ottawa Scale and the GRADE system. Results: Of the 1691 articles identified, 38 were included in the qualitative synthesis and 37 in the quantitative analysis. Three meta-analyses were developed and revealed the superiority of DIF over ELISA, with the following risk differences: BP180, 0.26 (95% CI: 0.19–0.33, p < 0.00001, I2: 96%); BP230, 0.59 (95% CI: 0.47–0.71, p < 0.00001, I2: 98%); and Lam332, 0.82 (95% CI: 0.70–0.94, p < 0.00001, I2: 89%). Conclusions: DIF remains the gold standard for the diagnosis of autoimmune SBDs. ELISA can serve as a complementary diagnostic tool, especially as a follow-up instrument for patients with SBD, owing to its low invasiveness.