Abstract
BACKGROUND: Acute appendicitis is the most common surgical emergency in children, yet timely and accurate diagnosis remains challenging due to nonspecific clinical presentations and limitations of imaging and blood tests. Saliva has emerged as a promising diagnostic medium because it is non-invasive, painless, inexpensive, and highly acceptable for pediatric patients. Salivary biomarkers may provide rapid and child-friendly adjuncts to existing diagnostic pathways. METHODS: A systematic literature search was performed in Ovid/MEDLINE, Scopus, Web of Science, and the Cochrane Library to identify studies assessing salivary biomarkers in pediatric appendicitis. Eligible studies included children with suspected or confirmed appendicitis and evaluated the diagnostic accuracy of salivary markers compared to clinical, laboratory, or imaging standards. RESULTS: To date, only three salivary biomarkers have been investigated. Leucine-rich α-2-glycoprotein 1 (LRG1) demonstrated high specificity of 100% but low sensitivity of 35-36%, with diagnostic accuracy ranging from AUC 0.77 to 0.85. C-reactive protein (CRP) showed excellent diagnostic performance with sensitivity of 91.3% and specificity of 95.4% (AUC 0.97), and strong correlation with serum CRP (ρ = 0.96). Irisin showed sensitivity of 90% and specificity of 60% with estimated AUC around 0.75, suggesting potential as an adjunct marker but limited as a standalone test. CONCLUSIONS: Salivary biomarkers in pediatric appendicitis are promising but remain underexplored, with evidence limited to small, single-center studies totalling fewer than 300 patients. Their advantages include feasibility, tolerability, and suitability for integration into point-of-care testing. Future research should focus on multicenter validation, development of multi-marker salivary panels, and application of biosensor technologies. With further evidence, salivary diagnostics could complement existing strategies and improve the accuracy and child-friendliness of appendicitis care.