Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick−associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N-acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms.

莱姆病是美国最常报告的媒介传播疾病，是由伯氏疏螺旋体感染引起的。这种疾病的早期临床诊断主要是基于高危地区个体存在红斑性皮肤病变。但是，这可以与其他疾病混淆，包括南方tick相关性皮疹疾病（STARI），该疾病缺乏明确的病原体或实验室诊断测试，并且在美国东部地区与莱姆病共存。通过对从特征明确的患者中获得的血清进行回顾性分析，采用无偏代谢组学方法，我们定义了早期莱姆病和STARI之间的生化和诊断差异。具体来说，由261个分子特征（MF）组成的代谢生物签名揭示了N的改变-酰基乙醇胺和伯脂肪酸酰胺的新陈代谢将STLY早期莱姆病区分开来。开发具有261-MF生物特征的分类模型并通过验证样品进行测试，可将早期莱姆病与STARI区别开，准确度为85％至98％。这些发现揭示了早期莱姆病和STARI之间的代谢差异，并通过客观地区分早期莱姆病和具有几乎相同症状的疾病，提供了一种强大的新方法来告知患者管理。