Persistent Lyme Symptoms: Patients Pay a High Price in Quality of Life
Persistent Lyme symptoms can substantially affect quality of life
Physical functioning may remain impaired after treatment
Work, productivity, and daily life can also suffer
Patients with persistent symptoms attributed to Lyme disease can experience substantially reduced quality of life even after previous antibiotic treatment.
A randomized trial from the Netherlands documented poor physical quality-of-life scores among patients with longstanding symptoms attributed to Lyme disease. More recent research from Belgium demonstrates that the burden can extend beyond symptom scores to employment, productivity, out-of-pocket expenses, and daily functioning.1,4
Quality of Life Was Severely Impaired
Berende and colleagues conducted the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE), a randomized clinical trial involving patients with persistent symptoms attributed to Lyme disease.1
At baseline, the mean physical-component summary score on the RAND SF-36 was 31.8, indicating substantial impairment in physical health-related quality of life.1
The investigators themselves noted that the patients had poor quality of life at baseline and that their scores reflected substantial impairment compared with the general population.1
Symptoms qualifying patients for the trial included musculoskeletal pain, arthritis, arthralgia, neuralgia, sensory disturbances, dysesthesia, neuropsychological or cognitive disorders, with or without persistent fatigue.
Quality of Life Remained Below Normal After Treatment
All participants received 2 weeks of intravenous ceftriaxone. They were then randomized to receive 12 additional weeks of doxycycline, clarithromycin plus hydroxychloroquine, or placebo.1
The mean physical-component score increased from 31.8 at baseline to 36.4 at the end of the 14-week treatment period, an improvement of 4.6 points.1
However, there was no significant difference in physical quality of life among the three randomized groups. The investigators concluded that the additional 12 weeks of oral antibiotic therapy did not provide greater improvement in health-related quality of life than the shorter regimen.1
Importantly, this does not mean that the patients returned to normal health. Quality of life remained below that of the general population despite the improvement observed during the study.1
What Does the PLEASE Trial Tell Us?
The PLEASE trial is often discussed primarily as a study of antibiotic duration. But it also documents something clinically important: patients presenting with persistent symptoms attributed to Lyme disease can have substantial impairment in physical quality of life.
The trial was not designed to determine why each patient’s symptoms persisted. The investigators acknowledged that the patient population was heterogeneous and that the underlying cause of persistent symptoms remained unclear.1
The study also cannot determine whether the improvement observed after enrollment resulted from the initial 2 weeks of ceftriaxone, nonspecific treatment effects, expectations, natural changes over time, or other factors because every participant received ceftriaxone before the randomized oral-treatment phase.1
Therefore, the trial provides useful information about the treatment regimens that were studied but does not resolve every question surrounding persistent symptoms following Lyme disease.
These Were Patients With Longstanding Symptoms
The patients enrolled in the PLEASE trial were not newly diagnosed patients being treated during the earliest stage of Lyme disease.
Many had experienced symptoms for years and had received previous antibiotic treatment. Median symptom duration was approximately 2 to 3 years across the treatment groups.1
Earlier U.S. randomized trials also enrolled patients with longstanding symptoms after previous treatment. In the Klempner trials, patients with persistent musculoskeletal pain, neurocognitive symptoms, dysesthesia, or fatigue had substantial impairment in health-related quality of life at baseline.2
This distinction matters when applying trial findings to individual patients. A patient with longstanding, previously treated symptoms may represent a different clinical situation from someone diagnosed and treated earlier in the course of illness.
Limits of Fixed Treatment Protocols
Randomized clinical trials require standardized treatment protocols so that outcomes can be compared between groups. That design is essential for answering the specific research question, but it differs from individualized clinical care.
In practice, patients with persistent symptoms may require reassessment of their original diagnosis, previous treatment response, symptom pattern, other tick-borne infections, autonomic dysfunction, sleep disturbance, medication effects, and unrelated medical conditions.
The PLEASE trial tested specific antibiotic regimens for defined periods. Its findings should therefore be interpreted as evidence about those regimens in that study population rather than as an explanation for every patient’s persistent symptoms.
The Burden Extends Beyond Quality-of-Life Scores
A 2023 Belgian study provides another way of looking at the impact of persistent symptoms after Lyme disease treatment.4
Willems and colleagues studied 187 patients with post-treatment Lyme disease syndrome (PTLDS). Rather than focusing primarily on antibiotic treatment response, the researchers examined healthcare use, out-of-pocket expenses, unemployment, and absence from work.
Mean annual direct costs were €4,618 per patient, with 49.5% paid out of pocket. Mean annual indirect costs were substantially greater at €36,081 per patient.4
These findings demonstrate that the burden experienced by patients with persistent symptoms may extend well beyond what is captured by a quality-of-life questionnaire.
Persistent Symptoms Can Affect the Ability to Work
The employment findings from the Belgian study were particularly striking.
Among the 187 participants, 87—or 46.5%—reported being unemployed or absent from work for more than one year because of Lyme disease.4
This does not mean that 46.5% of all patients with Lyme disease or PTLDS will experience long-term work loss. Participants were recruited through a Lyme disease patient organization, healthcare utilization and employment were self-reported, and the study population may have included patients with a greater illness burden than the broader population.4
Nevertheless, the study reinforces an important clinical point: persistent symptoms can have consequences that extend into employment, financial security, independence, and everyday functioning.
For more on employment, see How Lyme Disease Affects Employment and Productivity.
The True Cost Includes Daily Functioning
Quality of life is more than a laboratory result or symptom count.
Persistent fatigue may reduce stamina. Pain may interfere with physical activity. Cognitive difficulties can make concentration, memory, multitasking, and work more difficult. Dizziness, neurologic symptoms, and sleep disruption may further affect a patient’s ability to maintain normal daily activities.
The PLEASE trial documented substantial impairment in physical quality of life, while the Belgian study demonstrates how persistent illness can also be associated with major productivity and financial consequences.1,4
Together, these findings reinforce the importance of evaluating not only whether symptoms remain but also how those symptoms affect the patient’s ability to work, exercise, care for family members, participate socially, and function throughout the day.
Clinical Perspective
In my clinical practice, the effect of persistent symptoms on daily functioning is often as important as the individual symptoms themselves.
A patient may look relatively well during a brief office visit yet struggle to complete a full workday, maintain concentration, exercise, care for children, or perform ordinary household activities.
I have also seen patients diagnosed with persistent symptoms or PTLDS who improved with additional individualized treatment, while others did not. These clinical observations do not establish why symptoms persist or predict who will respond.
The appropriate approach is therefore individualized reassessment rather than assuming that every patient with persistent symptoms has the same underlying problem or will respond to the same intervention.
Frequently Asked Questions
Can Lyme disease affect quality of life?
Yes. Studies of patients with persistent symptoms following Lyme disease have documented substantial impairment in physical health-related quality of life, including fatigue, pain, cognitive difficulties, and reduced functioning.1,2
Do patients with persistent Lyme symptoms return to normal after treatment?
Outcomes vary. In the PLEASE trial, physical quality-of-life scores improved during the study but remained below those of the general population. The additional 12 weeks of oral antibiotics tested in the trial did not improve quality of life more than the shorter treatment regimen.1
Can persistent Lyme symptoms affect work?
They can. Fatigue, pain, cognitive difficulties, dizziness, sleep disruption, and neurologic symptoms may interfere with employment. In one Belgian PTLDS study, 46.5% of participants reported being unemployed or absent from work for more than one year because of Lyme disease, although this selected study population should not be considered representative of all Lyme disease patients.4
Does PTLDS explain why symptoms persist?
No. PTLDS describes a pattern of persistent symptoms following treatment but does not establish the underlying mechanism in an individual patient. Persistent infection, immune responses, residual bacterial material, tissue injury, nervous system changes, other illnesses, and additional mechanisms continue to be investigated.
Do clinical trials rule out individualized treatment?
Clinical trials provide important evidence about the particular treatments, durations, and patient populations studied. Individual patients may still require careful reassessment of their symptoms, previous treatment response, functional limitations, other possible diagnoses, and potential risks and benefits of additional treatment.
Clinical Takeaway
Persistent symptoms attributed to Lyme disease can be associated with substantial reductions in quality of life. The PLEASE trial documented markedly impaired physical functioning at baseline, and although patients improved during the study, their quality of life remained below that of the general population.1
More recent research demonstrates that this burden can extend beyond symptom and quality-of-life scores. In a Belgian study of patients with PTLDS, mean indirect costs substantially exceeded direct healthcare costs, and 46.5% of participants reported unemployment or absence from work lasting more than one year.4
These studies do not establish why symptoms persist in an individual patient or whether every patient will benefit from additional treatment. They do demonstrate that persistent symptoms can have meaningful consequences for physical functioning, employment, financial well-being, and daily life.
Patients with persistent symptoms deserve careful individualized reassessment rather than having the severity of their functional limitations judged solely by routine testing or a brief clinical examination.
This article is intended for informational purposes and does not provide medical advice.
Related Articles
Post-Treatment Lyme Disease Syndrome (PTLDS): Why Symptoms Persist
Persistent Lyme Disease Symptoms
How Lyme Disease Affects Employment and Productivity
How Much Does Lyme Disease Cost Patients and Society?
References
- Berende A, ter Hofstede HJM, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 2016;374(13):1209-1220. doi:10.1056/NEJMoa1505425.
- Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92. doi:10.1056/NEJM200107123450202.
- Berende A, ter Hofstede HJM, Donders ART, et al. Persistent Lyme Empiric Antibiotic Study Europe (PLEASE)—design of a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis. BMC Infect Dis. 2014;14:543. doi:10.1186/s12879-014-0543-y.
- Willems R, Verhaeghe N, Perronne C, Borgermans L, Annemans L. Cost of illness in patients with post-treatment Lyme disease syndrome in Belgium. Eur J Public Health. 2023;33(4):668-674. doi:10.1093/eurpub/ckad045.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
