Persistent Lyme disease

1.0 CME. This presentation provides physicians with clinically useful information that will help them assist patients with ongoing manifestations of Lyme disease following antibiotic therapy for Lyme disease.


Elizabeth Maloney, MD
Education Co-Director, Invisible International


The occurrence of persistent manifestations following antibiotic treatment of Lyme disease is well documented in the literature. This module uses a case discussion format to highlight: common ongoing manifestations of Lyme disease, potential pathophysiologic mechanisms for ongoing manifestations, the evaluation of patients who remain symptomatic and consideration of the trial evidence regarding antibiotic retreatment.

Learning objectives

  1. Understand that manifestations of Lyme disease can persist following antibiotic therapy
  2. Understand the evidence supporting the various proposed pathophysiologic mechanisms of persistent manifestations
  3. Understand the general process for evaluating patients with persistent manifestations and selecting appropriate therapy

This session, Persistent Lyme disease, is approved for 1.0 enduring AAFP Prescribed credit.

AAFP Prescribed credit is accepted by the American Medical Association as equivalent to AMA PRA Category 1 credit(s)™ toward the AMA Physician’s Recognition Award. When applying for the AMA PRA, Prescribed credit earned must be reported as Prescribed, not as Category 1.

The AAFP has reviewed One Health Medical Education for a Changing Climate and deemed it acceptable for AAFP credit. Term of approval is from 01/02/2024 to 01/01/2025. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Evidence-based bibliography for further study

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• Maloney EL. Controversies in Persistent (Chronic) Lyme Disease. J Infus Nurs. 2016 Nov/Dec;39(6):369-375. 

• Steere AC, Malawista SE et al. The clinical spectrum and treatment of Lyme disease. Yale J Biol Med 1984; 57(4):453-464. 

• Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994;21(3):454-461. 

• Shadick NA, Phillips CB, Logigian EL et al. The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. Ann Intern Med 1994;121(8):560-567. 

• Aucott JN, Rebman AW, Crowder LA, et al. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Qual Life Res. 2013 Feb;22(1):75-84. 

• Cameron D, Johnson L, Maloney e. Evidence Assessments and Guideline Recommendations in Lyme disease: The Clinical Management of Known Tick Bites, Erythema Migrans Rashes and Persistent Disease. Expert Review Anti-infect Ther. 2014 Sep;12(9):1103-1135. doi: 10.1586/14787210.2014.940900. 

• Rebman AW, Bechtold KT, Yang T. The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome. Front Med (Lausanne). 2017 Dec 14;4:224. doi: 10.3389/fmed.2017.00224. eCollection 2017. 

• Shor S, Green C, Szantyr B, Phillips S, Liegner K, Burrascano JJ Jr, Bransfield R, Maloney EL. Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group. Antibiotics (Basel). 2019 Dec 16;8(4). pii: E269. doi: 10.3390/antibiotics8040269. 

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• Eppes SC, Childs JA. Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics 2002; 109:1173-1177. 

• Dattwyler RJ, Volkman DJ, Conaty SM, Platkin SP, Luft BJ. Amoxicillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 1990; 336:1404-1406. 

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• Luft BJ, Dattwyler RJ, Johnson RC, et al. Azithromycin compared with amoxicillin in the treatment of erythema migrans: a double blind, randomized, controlled trial. Ann Intern Med 1996; 124:785-791. 

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• Jacek E, Fallon BA, Chandra A, Crow MK, Wormser GP, Alaedini A. Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits. J Neuroimmunol 2013 Feb 15;255(1-2):85-91. 

• Londoño D, Cadavid D, Drouin EE, Strle K, McHugh G, Aversa JM, Steere AC. Antibodies to endothelial cell growth factor and obliterative microvascular lesions in the synovium of patients with antibiotic-refractory lyme arthritis. Arthritis Rheumatol 2014 Aug;66(8):2124-2133. 

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• Aliota MT, Dupuis AP 2nd, Wilczek MP, Peters RJ, Ostfeld RS, Kramer LD. The prevalence of zoonotic tick-borne pathogens in Ixodes scapularis collected in the Hudson Valley, New York State. Vector Borne Zoonotic Dis 2014 Apr;14(4):245-250. doi: 10.1089/vbz.2013.1475. 

• Johnson TL, Graham CB, Maes SE, et al. Prevalence and distribution of seven human pathogens in host-seeking Ixodes scapularis (Acari: Ixodidae) nymphs in Minnesota, USA. Ticks Tick Borne Dis. 2018 Jul 20. pii: S1877-959X(18)30182-1. doi: 10.1016/j.ttbdis.2018.07.009. 

• Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC, Doyle-Meyers LA, Philipp MT, et al. Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding. PLoS One 2017 Dec 13;12(12):e0189071. doi: 10.1371/journal.pone.0189071. eCollection 2017. 

• Cerar D, Cerar T, Ruzić-Sabljić E, Wormser GP, Strle F. Subjective symptoms after treatment of early Lyme disease. Am J Med 2010 Jan;123(1):79-86. 

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About Instructor

Elizabeth L. Maloney, MD

Dr. Elizabeth Maloney is a Minnesota family physician. She received her medical degree from the University of Minnesota in 1986 and completed her residency in family medicine at the University in 1989. Early in her career, she practiced in Guam, where lab and other testing modalities were often unavailable. It was here that she honed her clinical skills and learned to translate history and exam findings into clinical diagnoses and treatment plans. Dr. Maloney began reviewing the scientific literature on tick-borne diseases in earnest in 2006. Her initial review was an attempt to understand why some patients did not present or respond as described in review articles and conference lectures. When she discovered that Borrelia burgdorferi, the agent of Lyme disease, is a complex organism, the immune response to it is nuanced and there are gaps in the clinical understanding of Lyme disease, Dr. Maloney changed her focus towards educating medical professionals about tick-borne illnesses. Dr. Maloney began providing accredited continuing medical education courses on Lyme disease for physicians in 2007 and continues to do so. She has also developed similar education for nurses and mental health providers. She has published several papers in peer-reviewed medical journals and is frequently invited to speak to medical professionals across the US. She has served as a consultant to private organizations and government agencies in the US and Canada. In February 2018 she was selected to serve on the Pathogenesis, Transmission and Treatment subcommittee of the federally mandated Tick-borne Disease Working Group. Additionally, she recently accepted an invitation to serve on a peer review committee for the Canadian Institutes of Health Research.

12 Courses

Not Enrolled

Course Includes

  • 1 Lesson
  • 2 Quizzes
  • Course Certificate