This is the largest peer-reviewed prospective controlled study in the US that specifically focuses on the longer-term outcomes of early diagnosed and promptly treated Lyme disease patients. Results found that functionally impairing persistent symptoms occurred in 14% of the early treated Lyme disease patients compared with 4% in the healthy control group. Results confirm that Lyme disease can trigger persistent symptoms, such as severe fatigue, body pain and cognitive challenges, despite early treatment with standard of care antibiotics.
Why was this study done?
This study specifically focused on the longer-term outcome of Lyme disease patients and was rigorously designed to determine if persistent patient-reported symptoms following early diagnosis and prompt treatment for Borrelia burgdorferi (Lyme disease) infection are significant and distinguishable from those found in healthy non-Lyme controls.
How was this study done?
This longitudinal, prospective controlled study was conducted on 234 early diagnosed and treated patients who met a standardized criteria for acute Lyme disease: prior documented Lyme disease with an erythema migrans rash, no other specific co-morbidities. Patients were evaluated for both specific symptoms and functional impact of symptoms at 6-12 months following their initial Lyme disease diagnosis and treatment. As a control arm of the study the same symptom and functional impact criteria were applied to a comparable cohort of 49 healthy people without prior Lyme disease. The study is the first to also examine and control for the impact of potential confounders, including sex, race, education, heart disease/hypertension, mental health disorders, depression, and prior traumatic life events.
All participants completed a comprehensive standardized series of well validated symptom-based surveys for fatigue, pain, sleep, depression, cognitive symptoms, and quality of life. Clinical outcomes and symptoms were analyzed and compared to non-Lyme infected controls.
What were the major findings?
In this study, 234 patients with early well documented Lyme disease were compared to healthy controls without a history of Lyme disease. When examined 6-12 months after initial antibiotic treatment, 14% of the Lyme disease patients continued to have persistent symptoms (including fatigue, pain, and cognitive symptoms) that impacted quality of life, which was significantly higher than the 4% of the control population exhibiting persistent symptoms.
Participants with prior Lyme disease were approximately 5 times as likely to meet symptom and functional impact criteria for post treatment Lyme disease compared to those without prior Lyme disease. They also had higher joint pain, memory problems and depression and 2-3 times as high odds of reporting moderate or severe fatigue and muscle pain. Results were highly statistically significant and indicate symptoms were not just the mild fatigue and pain of everyday living but rather severe fatigue and pain that impacted quality of life.
Females were 4 times as likely as males to meet post treatment Lyme disease criteria than return to health criteria, and for each increase in potentially traumatic life event, the risk of meeting post treatment Lyme disease criteria increased 30%. More research is needed to determine if female sex and/or increased exposure to traumatic life events impact the initial biologic response to Borrelia burgdorferi infection and increase the risk for persistent symptoms.
What is the impact of this work?
Symptom persistence of 14% falls within the 10-20% range of estimated persistent symptom prevalence previously described in the Lyme disease literature. This result likely underestimates the true rate of persistent symptoms since this study of early diagnosed and treated patients does not account for the substantial number of misdiagnosed and delayed diagnosed cases experienced in a non-study setting where prolonged illness risk would be expected to be greater. In complicated patients such as those with a delayed diagnosis or other later manifestations of Lyme disease, persistent illness risk may be closer to 20% to 30%.
With 476,000 new cases annually in the US, the “long haul” impact of Lyme disease is clearly a substantial public health concern.
The main symptoms of post treatment Lyme disease are fatigue, generalized pain and cognitive dysfunction. These core symptoms are similar to those seen in other infection associated persistent illnesses such as long COVID and ME/CFS. More research is needed to determine if there are common mechanisms of inflammation, immune response dysregulation, autonomic nervous system dysfunction, or pathogen or antigen persistence that underlie these infection associated chronic illnesses.
This research was supported by:
the Steven and Alexandra Cohen Foundation; the Global Lyme Alliance (GLA); and the Bay Area Lyme Foundation (BALF). This publication was also made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, and the Johns Hopkins Clinical Research Network (JHCRN).
Study team members:
John N. Aucott MD1*, Ting Yang PhD1, Isaac Yoon MD2, Debra Powell MD3, Steven A. Geller MD4, Alison W. Rebman MPH1
1Lyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2Patient First, Lutherville, MD USA
3Reading Hospital Tower Health, West Reading, PA, USA
4Centennial Medical Group, Elkridge, MD, USA
Risk of post-treatment Lyme disease in patients with ideally-treated early Lyme disease: A prospective cohort study.Aucott, John N. et al.International Journal of Infectious Diseases, Volume 116, 230 – 237
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