Admission Blood Biomarkers for Differentiating Acute Appendicitis from Acute Enteritis in Children Younger than Five Years: A Retrospective Cohort Study

Background/Objectives: Acute abdominal pain in children younger than five years is a diagnostic challenge because acute appendicitis and acute enteritis share overlapping clinical features, and delayed recognition of appendicitis increases the risk of perforation and postoperative complications. We aimed to identify admission blood biomarkers that reliably distinguish these two conditions and to quantify their diagnostic accuracy. Methods: We conducted a retrospective observational cohort study at the Children’s Hospital Zagreb covering the period from 1 January 2016 to 1 January 2026. Children younger than five years with a confirmed diagnosis of acute appendicitis (Group A, n = 80) or acute enteritis (Group B, n = 66) were included. Appendicitis was confirmed intraoperatively and histopathologically, whereas enteritis was confirmed by stool testing, imaging, and clinical course. The complete blood count with differential, derived inflammatory indices, and C-reactive protein obtained on admission were compared using the Mann–Whitney U test, receiver operating characteristic analysis, and multivariable logistic regression. Results: Appendicitis was associated with higher neutrophil percentage, neutrophil-to-lymphocyte ratio, C-reactive protein, and composite systemic inflammatory indices, whereas enteritis showed higher lymphocyte percentage, eosinophil percentage, and platelet count. The strongest single discriminators were C-reactive protein (area under the curve 0.91), neutrophil percentage (0.90), and the neutrophil-to-lymphocyte ratio (0.90). A multivariable model combining log-transformed C-reactive protein and neutrophil-to-lymphocyte ratio reached an apparent area under the curve of 0.96, with an optimism-corrected value of 0.95, and 96.3% sensitivity and 86.4% specificity, and both markers were independent predictors of appendicitis. Children with appendicitis also more often showed rebound tenderness and right lower quadrant tenderness, complicated appendicitis was present in 78.8% of them, and among operated children, a higher immature granulocyte fraction and count were associated with complicated disease in an exploratory analysis. Conclusions: Simple and inexpensive blood biomarkers available on admission, in particular C-reactive protein and the neutrophil-to-lymphocyte ratio, are strongly associated with the final diagnosis and discriminate acute appendicitis from acute enteritis in children younger than five years. Prospective validation in consecutive children with diagnostic uncertainty is needed before they can be used to guide clinical decisions.