Research ArticleInfectious diseases

Metabolic differentiation of early Lyme disease from southern tick–associated rash illness (STARI)

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Science Translational Medicine  16 Aug 2017:
Vol. 9, Issue 403, eaal2717
DOI: 10.1126/scitranslmed.aal2717

Avoiding rash decisions

The iconic bulls eye rash is associated with Lyme disease, but similar symptoms are observed in other illnesses not caused by Borrelia burgdorferi infection, such as southern tick–associated rash illness, which has not yet been tied to a specific pathogen. Molins et al. set out to define a metabolic signature that would be able to distinguish early Lyme disease from southern tick–associated rash illness. Their findings confirm that these diseases are quite distinct. Moreover, use of the signature could help guide diagnosis and patient treatment.


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.

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