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A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist

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Abstract

Lyme disease is an infection caused by Borrelia burgdorferi sensu lato, which is transmitted to humans through the bite of an infected Ixodes tick. The majority of patients recover without complications with antibiotic therapy. However, for a minority of patients, accompanying non-specific symptoms can persist for months following completion of therapy. The constellation of symptoms such as fatigue, cognitive dysfunction, and musculoskeletal pain that persist beyond 6 months and are associated with disability have been termed post-treatment Lyme disease syndrome (PTLDS), a subset of a broader term “chronic Lyme disease.” Chronic Lyme disease is a broad, vaguely defined term that is used to describe patients with non-specific symptoms that are attributed to a presumed persistent Borrelia burgdorferi infection in patients who may or may not have evidence of either previous or current Lyme disease. The diagnoses of chronic Lyme disease and of PTLDS have become increasingly relevant to the practice of immunologists due to referrals for consultation or for intravenous immunoglobulin (IVIG) treatment. This review aims to explore the relationship between chronic Lyme disease, post-treatment Lyme disease syndrome, and the immune system. Here, we review the current literature on (1) issues in conventional and alternative diagnostic testing for Lyme disease, (2) the hypothesis that B. burgdorferi infection can persist despite appropriate use of recommended antibiotics, (3) current theories regarding B. burgdorferi’s role in causing both immune dysregulation and protracted symptoms, and (4) the use of IVIG for the treatment of Lyme disease.

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Funding

This work was supported, in part, by the following grants: UL1TR000142 (E.D.S.) and KL2-TR001862 (E.D.S) from the National Center for Advancing Translational Science (NCATS) at the National Institutes of Health and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH.

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  1. Department of Pediatrics, Yale School of Medicine, 330 Cedar Street, LMP 5039, New Haven, CT, 06520, USA

    Katelyn H. Wong, Eugene D. Shapiro & Gary K. Soffer

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All authors contributed to the review article conception and literature search. The first draft of the manuscript was written by Katelyn Wong and all authors modified subsequent versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Katelyn H. Wong.

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Dr. Shapiro has served as an expert witness, has received an honorarium for consulting with Pfizer, and receives royalties from UptoDate.

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Wong, K.H., Shapiro, E.D. & Soffer, G.K. A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist. Clinic Rev Allerg Immunol 62, 264–271 (2022). https://doi.org/10.1007/s12016-021-08906-w

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