Skin and subcutaneous conditions affect an estimated 1.9 billion people at any given time and remain the fourth leading cause of non-fatal disease burden worldwide.Access to dermatology care is limited due to a shortage of dermatologists, causing long wait times and leading patients to seek dermatologic care from general practitioners.However, the diagnostic accuracy of general practitioners has been reported to be only 0. 24-0. 70 (compared to 0. 77-0. 96 for dermatologists), resulting in over-and under-referrals, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 of the most common skin conditions, representing roughly 80% of the volume of skin conditions seen in a primary care setting. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively, indicating the fraction of cases where the DLS's top diagnosis and top 3 diagnoses contains the correct diagnosis. For a stratified random subset of the validation set (n=963 cases), 18 clinicians (of three different training levels) reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs . These results highlight the potential of the DLS to augment the ability of general practitioners who did not have additional specialty training to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.

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IMPORTANCE Most dermatologic cases are initially evaluated by nondermatologists such as primary care physicians (PCPs) or nurse practitioners (NPs). OBJECTIVE To evaluate an artificial intelligence (AI)-based tool that assists with diagnoses of dermatologic conditions. DESIGN, SETTING, AND PARTICIPANTS This multiple-reader, multiple-case diagnostic study developed an AI-based tool and evaluated its utility. Primary care physicians and NPs retrospectively reviewed an enriched set of cases representing 120 different skin conditions. Randomization was used to ensure each clinician reviewed each case either with or without AI assistance; each clinician alternated between batches of 50 cases in each modality. The reviews occurred from February 21 to

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