Reproducibility of Patch Test Reactions and Interpretation of Doubtful Results: A Retrospective Study of Identical Haptens Tested Simultaneously in Different Series

BACKGROUND: Reproducibility of patch test reactions remains debated, and the clinical significance of doubtful (?+) reactions is unclear. OBJECTIVES: To evaluate reproducibility of positive reactions to identical haptens tested simultaneously in different series and analyse doubtful reactions using paired co-reactivity patterns. MATERIALS AND METHODS: Patch test data from consecutive patients tested during 2015-2025 were analysed retrospectively. Six haptens were evaluated at standard concentrations in petrolatum: hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral, HICC) 5% pet., Amerchol L-101 50% pet., lanolin alcohol 30% pet., hydroxyethyl methacrylate (HEMA) 2% pet., mercaptobenzothiazole (MBT) 2% pet. and Myroxylon pereirae resin (balsam of Peru, MPR) 25% pet. RESULTS: Reproducibility was hapten-dependent. HEMA and MBT showed substantial to almost perfect agreement. HICC showed substantial agreement but a significantly higher positivity rate in the perfume series than in the baseline series. Amerchol L-101, lanolin alcohol and MPR showed lower positive agreement and fair-to-moderate kappa values. Most doubtful reactions were isolated, particularly for Amerchol L-101 and lanolin alcohol, whereas 43.8% of doubtful HICC reactions in the baseline series were supported by perfume-series reactivity. CONCLUSIONS: Reproducibility was strongly hapten-dependent. In this dataset, paired co-reactivity provided clinical context for interpreting discordant positive and doubtful reactions.