Optimal biopsy site for the diagnosis of oral pemphigus vulgaris and mucous membrane pemphigoid: a systematic review and meta-analysis

The aim of this study was to critically evaluate the diagnostic yields of direct immunofluorescence (DIF) analysis on perilesional and normal-appearing mucosa biopsy samples, to determine the optimal biopsy site for patients presenting with oral pemphigus vulgaris (PV) or mucous membrane pemphigoid (MMP). Electronic databases and article bibliographies were searched in December 2022. The primary outcome was the rate of DIF positivity. Of 374 records identified after the elimination of duplicates, 21 studies with 1027 samples were ultimately included. Meta-analysis revealed a pooled DIF positivity rate of 99.6% (95% confidence interval (CI) 97.4–100.0%, I2 = 0%) for PV and 92.6% (95% CI 87.9–96.5%, I2 = 44%) for MMP for biopsies from perilesional sites, and of 95.4% (95% CI 88.6–99.5%, I2 = 0%) for PV and 94.1% (95% CI 86.5–99.2%, I2 = 42%) for MMP for biopsies from normal-appearing sites. For MMP, there was no significant difference in the rate of DIF positivity between the two biopsy sites (odds ratio 1.91, 95% CI 0.91–4.01, I2 = 0%). The results suggest that the perilesional mucosa remains the optimal biopsy site for DIF diagnosis of oral PV, while the normal-appearing mucosa biopsy is optimal for oral MMP.