Diagnostic Performance of Interleukin-6 (IL-6) and Membrane Glycoprotein Cluster of Differentiation-64 (CD64) for Acute Appendicitis in Girls Presenting with Lower Abdominal Pain.
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Background: Acute appendicitis in girls presenting with lower abdominal pain remains a frequent diagnostic dilemma because of the overlap in clinical presentation with gynaecological and non-surgical causes. This study aimed to evaluate the diagnostic performance of IL-6 and CD64 and to compare them with classical inflammatory markers and the Alvarado score. Methods: We conducted a prospective observational diagnostic-accuracy study over a three-year period (December 2022 to December 2025) at the First University Paediatric Surgery Clinic, General Hospital of Thessaloniki "Georgios Gennimatas". Consecutive girls aged ≤16 years presenting with lower abdominal pain were included. The primary outcome was appendicitis (yes/no), defined by the final clinical diagnosis and, where applicable, intraoperative and/or histopathological confirmation. Diagnostic performance was assessed using ROC curves and AUCs with 95% confidence intervals estimated by the DeLong method. The prespecified primary regression model included the Alvarado score and IL-6; IL-6 was summarised on its original scale and log1p-transformed only for regression analyses to account for right-skewness. Additional multivariable models were exploratory. Results: Of 74 initially assessed cases, one was excluded (appendiceal neuroendocrine tumour, NET G1), yielding a final sample of 73 girls: 37 with appendicitis and 36 without appendicitis. IL-6 was higher in the appendicitis group (median 19.41 vs. 4.10 pg/mL) and showed moderate discrimination (AUC 0.696). CRP showed lower to borderline performance (AUC 0.595), whereas CD64 did not demonstrate useful discrimination (AUC 0.521). The Alvarado score had the highest discriminatory ability (AUC 0.885). In the subset with complete data, adding IL-6 to the Alvarado score did not materially improve discrimination. Conclusions: IL-6 showed moderate diagnostic performance as a standalone biomarker and may be useful as an adjunct, particularly when a clinical score is unavailable or unreliable. CD64 did not add meaningful diagnostic information in this setting. Larger, prespecified studies are required to determine clinically useful cut-offs and to clarify whether IL-6 offers incremental value beyond established clinical assessment.