Diagnostic agreement and accuracy of dermatopathology versus molecular PCR test in distinguishing eczema from psoriasis

BackgroundTargeted 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. ObjectiveWe aimed at assessing the diagnostic performance of both a manual (MC) and fully automated (PsorX-LabDisk) RT-qPCR test based on the expression of NOS2 and CCL27 compared with conventional dermatopathological evaluation in differentiating psoriasis from eczema. MethodsSeventy-three FFPE skin samples of psoriasis and eczema were randomly selected and evaluated histopathologically (H&E-stained sections) by 14 dermatopathologists to assess interobserver variability, quantified using Cohens and Fleiss {kappa}. 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 were determined against reference diagnoses. ResultsDermatopathological evaluation demonstrated only fair agreement (Fleiss {kappa} = 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%). ConclusionsBoth 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. Key pointsO_ST_ABSHigh interobserver variability in dermatopathologyC_ST_ABSAcross two independent cohorts, dermatopathological evaluation by multiple dermatopathologists showed only fair to no agreement, highlighting substantial subjectivity and diagnostic uncertainty in distinguishing psoriasis from eczema based solely on morphology. Superior accuracy of molecular diagnosticsBoth the manual (MC) and fully automated NOS2/CCL27-based RT-qPCR (PsorX-LabDisk) assays outperformed dermatopathology, achieving sensitivities around 93 % and overall accuracies around 88 %, demonstrating that molecular testing provides a more consistent and objective diagnostic approach. Robust performance in ambiguous casesIn diagnostically challenging samples with low dermatopathological consensus, the PsorX-LabDisk maintained high diagnostic accuracy (>86 %), outperforming expert evaluation. These results underscore its potential as a reliable, examiner-independent tool supporting precise diagnosis and optimized treatment selection in clinical practice. Capsule SummaryBoth MC and PsorX-LabDisk molecular assay outperformed dermatopathology in differentiating psoriasis from eczema, offering an objective, reproducible, and clinically practical tool that enhances diagnostic confidence and guides targeted treatment in inflammatory skin diseases.