Diagnostic Value of In Vitro Tests for Peanut Allergy in Children Without Clinical Exposure: A High-Specificity Rule-In Decision Pathway—Preliminary Findings from a Single-Center Study in Polish Children

<b>Background:</b> Diagnosing peanut allergy (PA) in children without known exposure remains challenging due to the need to distinguish true clinical allergy from asymptomatic sensitization. This study aimed to evaluate the diagnostic performance of individual and combined in vitro markers, particularly sIgE to Ara h 2, and to develop a multistage decision pathway that may reduce reliance on oral food challenge (OFC). <b>Methods:</b> Eighty children with suspected peanut allergy were prospectively enrolled. All participants, including healthy controls, underwent skin prick testing (SPT), measurement of sIgE to peanut and Ara h 2, and basophil activation testing (BAT). A multistage diagnostic algorithm incorporating these markers was constructed, and its performance was assessed using ROC analysis, predictive values, and likelihood ratios. A secondary analysis evaluated a simplified decision pathway excluding BAT. <b>Results:</b> sIgE to Ara h 2 demonstrated excellent individual performance (AUC 0.889), with 96.6% PPV at the optimal cut-off. The full multistage decision pathway (SPT + sIgE + BAT when interpretable) achieved 100% specificity and avoided OFC in 28.6% of children. However, BAT feasibility was limited; over 25% of results were uninterpretable. The simplified decision pathway (SPT + sIgE to Ara h 2) preserved 100% specificity and enabled the avoidance of OFC in 27.5% of cases, with slightly lower sensitivity. <b>Conclusions:</b> A structured in vitro diagnostic approach using sIgE to Ara h 2 and SPT can reliably identify peanut allergy in selected pediatric patients, particularly those without a reliable peanut exposure history. BAT enhances specificity but should be considered a confirmatory tool due to feasibility limitations.