Andrea Schmitt, Susanne Proksch, Ludwig Gutzweiler, Sandra Roth, Marcella Engler, F. Max Müller, Andreas Völz, Andreas Arnold, Monika Šedivcová, Adriana Bernklauova, Miroslav Důra, Denisa Kacerovská, Katja Technau‐Ihling, Christian Ihling, Christiane Rakozy, Wiebke Pruessmann, Thomas Leibing, Maria Isabel von Eichborn, Johannes Kern, Elisabeth Oms, Stefanie Eyerich, Kilian Eyerich, H. Laaff, Natalie Garzorz‐Stark, Kristin Technau‐Hafsi
BACKGROUND: Targeted treatments for non-communicable chronic inflammatory skin diseases like eczema and psoriasis offer significant potential for effective therapy. However, therapeutic success requires an accurate diagnosis, which is challenging due to their overlapping clinical and histological features. OBJECTIVES: We aimed at assessing the diagnostic performance of both a manual (MC) and fully automated (PsorX-LabDisk) quantitative real-time polymerase chain reaction (RT-qPCR) test based on the expression of NOS2 and CCL27 compared with conventional dermatopathological evaluation in differentiating psoriasis from eczema. METHODS: Seventy-three formalin-fixed, paraffin-embedded skin samples of psoriasis and eczema were randomly selected and evaluated histopathologically (H&E-stained sections) by 14 dermatopathologists to assess inter-observer variability, quantified using Cohen's and Fleiss' κ. To confirm that the observed variability was not cohort- or rater-specific, a validation cohort (n = 72) from an independent institution was assessed by three dermatopathologists under identical conditions. For molecular analysis, both manual (MC) and automated NOS2/CCL27-based RT-qPCR (PsorX-LabDisk) workflows were applied. Diagnostic performance (sensitivity, specificity, accuracy) of histopathological and molecular analyses was determined against reference diagnoses. RESULTS: Dermatopathological evaluation demonstrated only fair agreement (Fleiss' κ = 0.31) in both study and validation cohort. The mean diagnostic accuracy of dermatopathology was 76.9%, with a sensitivity of 70% and specificity of 81.6%. In comparison, MC and the PsorX-LabDisk achieved sensitivities of both 92.9%, specificities of 82.2% and 84.4% and accuracies of 87.7% and 86.3%, respectively. In diagnostically ambiguous cases, molecular testing maintained high accuracy (>86%), clearly outperforming dermatopathology, which showed near-random agreement and low accuracy (61.7%). CONCLUSIONS: Both MC and PsorX-LabDisk provide a reliable, examiner-independent complement to dermatopathology for differentiating psoriasis and eczema. By reducing diagnostic ambiguity, it enhances clinical confidence and supports more precise and timely therapeutic decisions in inflammatory skin disease management.