Histologic Features of Secondary Syphilis: A Systematic Review and Meta-Analysis

Secondary syphilis, caused by Treponema pallidum and known as the "the great imitator," presents with varied manifestations that may mimic other skin conditions. Histopathology is critical when clinical or serologic findings are atypical, and this study analyzed its key features to improve recognition and reduce diagnostic errors. A systematic search was conducted in PubMed, Embase, and Cochrane. Statistical analyses were performed using R, version 4.3.2. A random-effects model was used to determine the proportion with 95% confidence interval (CI). Heterogeneity was assessed using Cochrane Q test and I2 statistics. Eight studies encompassing 384 patients and 460 lesions were included. The mean age was 38.1 years, and approximately 24% of the patients were female. The most common histological features were endothelial swelling, reported by five studies, with a prevalence of 85% (95% CI 0.75-0.96; I2 = 82.6%), and moderate to dense plasma cell infiltration, as reported by six studies, with a prevalence of 83% (95% CI 0.74-0.92; I2 = 90.7%). Acanthosis was observed in six studies, with a prevalence of 66% (95% CI 0.47-0.86; I2 = 96.0%), followed by perivascular inflammatory infiltrate, reported in five studies, with a prevalence of 64% (95% CI 0.37-0.90; I2 = 96.9%). Histopathology reveals consistent features, particularly endothelial swelling and plasma cell-rich infiltrates, in secondary syphilis, reinforcing its diagnostic value when clinical or serologic findings are inconclusive.