Clinically Interpretable Deep Learning for Differentiating Vitiligo and Postinflammatory Hypopigmentation: Diagnostic Accuracy Study.

Background: Distinguishing vitiligo from postinflammatory hypopigmentation (PIH) is clinically challenging because both conditions may present with similar depigmented lesions. Although deep learning has shown strong potential for dermatologic image classification, limited interpretability remains a barrier to clinical adoption. Objective: This study aimed to develop an interpretable deep learning framework for accurate differentiation between vitiligo and PIH using a lightweight convolutional neural network and an ensemble of explainability methods. Methods: A total of 332 clinical images (176 vitiligo and 156 PIH) were collected from King Abdullah University Hospital and publicly available online sources. Images were preprocessed and evaluated using patient-wise 5-fold cross-validation to eliminate patient-level data leakage. A pretrained MobileNetV2 model was fine-tuned by unfreezing the final 30 layers. To enhance interpretability, gradient-weighted class activation mapping (Grad-CAM), integrated gradients, and smooth gradients (SmoothGrad) were combined into an equal-weight ensemble explanation framework. Performance was assessed using accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC). Results: The proposed model achieved an overall accuracy of 94.88%, macroaveraged precision of 94.88%, recall of 94.84%, F1-score of 94.86%, and an AUC of 0.9885 across the 5 validation folds. The ensemble framework produced clinically meaningful explanations in 98.48% of a representative 66-image validation subset used for interpretability analysis. Conclusions: The proposed framework combines high diagnostic performance with robust interpretability for distinguishing vitiligo from PIH. By integrating multiple complementary explanation methods, the approach enhances clinical transparency and may support dermatologists in the differential diagnosis of pigmentary disorders.