This study investigated the feasibility of predicting disease flares in dermatomyositis (DM) using interferon gene signatures from blood samples. Six female DM patients aged 46-72 years were enrolled and self-assessed their disease activity weekly for 6 months while collecting home-based blood microsamples. Three disease flares occurred during the follow-up period. Analysis of 54 samples from 9 timepoints using RNA sequencing showed that interferon scores were significantly higher in flare-associated samples compared to non-flare samples (P = 5.13 x 10E-4). Interferon alpha and interferon gamma gene signatures were particularly elevated before and during flares. The study demonstrated the technical feasibility of combining home-based blood microsampling with gene expression analysis for monitoring DM disease activity.