Rare Disease Diagnosis Agent with Decoupled Workflows and Knowledge-Driven Self-Evaluation

Rare disease diagnosis is a fundamental challenge due to heterogeneous and overlapping clinical phenotypes. While recent LLM-based agentic systems have demonstrated promise by integrating external medical tools and knowledge, they typically rely on large-scale or commercial LLMs, limiting their practical deployment in resource-constrained settings. In this work, we observe that their performance significantly degrades when using small-scale LLMs, due to entangled workflows and unreliable multi-evidence aggregation. To address this issue, we propose RADAR, a rare disease diagnostic framework designed for small-scale LLMs. RADAR adopts a divide-and-conquer paradigm that decouples heterogeneous diagnostic evidence into specialized workflows, reducing reasoning complexity and improving robustness. It further introduces a knowledge-driven self-evaluation mechanism that performs evidence-aware reasoning over structured disease knowledge to produce interpretable reliability scores by identifying key supporting phenotypes and conflicting evidence. Finally, a multi-evidence fusion strategy integrates outputs from multiple sources based on reliability and clinical agreement, resolving conflicts and producing stable diagnostic rankings. Experiments on three benchmarks show that RADAR consistently outperforms various state-of-the-art baselines, including general and medical LLMs and agentic systems. Code will be released.