BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of flares and remission. Designing personalized treatment strategies for AD is challenging, given the apparent unpredictability and large variation in AD symptoms and treatment responses within and across individuals. Better prediction of AD severity over time for individual patients could help to select optimum timing and type of treatment for improving disease control. OBJECTIVE: We aimed to develop a proof of principle mechanistic machine learning model that predicts the patient-specific evolution of AD severity scores on a daily basis. METHODS: We designed a probabilistic predictive model and trained it using Bayesian inference with the longitudinal data from two published clinical studies. The data consisted of daily recordings of AD severity scores and treatments used by 59 and 334 AD children over 6 months and 16 weeks, respectively. Validation of the predictive model was conducted in a forward-chaining setting. RESULTS: Our model was able to predict future severity scores at the individual level and improved chance-level forecast by 60%. Heterogeneous patterns in severity trajectories were captured with patient-specific parameters such as the short-term persistence of AD severity and responsiveness to topical steroids, calcineurin inhibitors and step-up treatment. CONCLUSIONS: Our proof of principle model successfully predicted the daily evolution of AD severity scores at an individual level and could inform the design of personalized treatment strategies that can be tested in future studies. Our model-based approach can be applied to other diseases with apparent unpredictability and large variation in symptoms and treatment responses such as asthma.