Dr. Ric Arseneau (biography and disclosures)
Disclosure: Dr. Arseneau is the Director of Program Planning and a clinician at the Complex Chronic Diseases Program (CCDP). Mitigating Potential Bias: Recommendations are consistent with current practice patterns.
What I did before
Chronic Lyme Disease (CLD) is not a widely accepted medical term. A search for CLD on UpToDate (1) leads to a section entitled “POST-LYME DISEASE SYNDROME AND CHRONIC LYME DISEASE.” UpToDate states that the “currently available evidence does not support the hypothesis that persistent infection with B. burgdorferi is the cause of chronic subjective symptoms” attributed to Lyme disease and recommends against the use of antibiotics in this patient population. They go on to say that the majority of patients diagnosed with “chronic Lyme disease” (quotes used by UpToDate) “have no evidence of having had Lyme disease.”
Patient advocacy groups would beg to differ. As a result of patient advocacy and a private members bill in parliament, a conference to develop a federal framework on Lyme disease was held in Ottawa in May of 2016. (2) The Medical Post covered the conference in a recent issue. (3)
Post-Treatment Lyme Syndrome is a distinct syndrome seen in patients with documented Lyme disease. Patients have persistent non-specific symptoms after adequate antibiotic treatment. The symptoms include the constellation of fatigue, pain, sleep disturbance, and unexplained symptoms. Readers might remember this constellation of symptoms from two prior TCMP I did: one on Central Sensitivity Syndromes (CSS) (4) and the other on Chronic Fatigue Syndrome (CFS). (5) Some authors believe, like I do, that Post-Treatment Lyme Syndrome is a CSS. (6)
CLD is also likely a CSS. A study by Dr. David Patrick and the Complex Chronic Diseases Program (CCDP), found that patients with symptoms attributed CLD could not be distinguished from patients with CFS. (7) This has also been my experience at the CCDP. Patient who come in with the label CLD almost invariable fulfill diagnostic criteria for CFS or fibromyalgia (FM). Furthermore, the Mayo Clinic also considers CLD a CSS. (8)
Borrelia burgdorferi (the Lyme bacterium) is found in only 1 in 200 ticks in southern BC. (9) Therefore, the vast majority of patients with symptoms attributed CLD in BC do not have PTLS. These patients are negative for Lyme serology by reference lab testing. Most have a positive Lyme test by an independent lab offering a non-validated Lyme diagnostic test in the USA. Given the low prevalence of Lyme disease in BC, it is estimated that false-positive diagnoses from a commercial laboratory can exceed true positives by a ratio of at least 50 to 1. (7) The FDA is also concerned with the number of false positives for Lyme disease from commercial labs. (9) A CCDP Lyme Testing Fact Sheet is available for clinicians containing more information on which tests to watch out for: view. (10)
Despite the lack of evidence, many patients continue to get long term antibiotic treatment for symptoms attributed to CLD at a significant cost: financial and morbidity. For physicians interested in reading more about the misconceptions and challenges of CLD, I would suggest the excellent narrative review by Dr. John Halparin. (12) A St. Paul’s Hospital Grand Rounds presentation I did on the controversies surrounding CLD is also available on-line. (13)
I approach patients with symptoms attributed to CLD knowing that they often suffer debilitating symptoms and disability. Unfortunately, their experience with the medical community has often been frustrating and demoralizing. The key is not to be pulled into a debate about contested causation: whether persistent Borrelia infection is at the root of their symptoms. The focus should be on helping patients with their symptoms. Some patients who are not committed to the concept of persistent infection may accept a diagnosis of CFS (or FM). They often respond positively to the use of CSS in explaining their symptoms.
What changed my practice
The PLEASE trial (Persistent Lyme Empiric Antibiotic Study Europe) (14, 15) was published in the New England Journal of Medicine in March 2016. This randomized, double-blind, placebo-controlled study assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment. Participants received a 12-week oral course of doxycycline, clarithromycin plus hydroxychloroquine, or placebo. All study groups received open-label intravenous ceftriaxone for 2 weeks before initiating the randomized regimen. 280 patients were included in the trial. To participate in the study, patients needed a proven history of Lyme disease (history of target rash or positive serology). This is significant, as this is the group most likely to benefit from antibiotics if their symptoms were caused by persistent infections (as opposed to those with a dx of CLD as a result of false positive testing from independent non-validated labs). In the end, longer-term antibiotic treatment did not have an additional beneficial effect on health-related quality of life beyond those with shorter-term treatment. The results were consistent with those from prior randomized, placebo-controlled trials.
An accompanying editorial in the same issue of the NEJM (16) suggests that because “molecular or culture methods did not find evidence of persistent infection in the enrolled patients, it was perhaps not surprising that additional antimicrobial therapy yielded neither clinically significant nor durable reductions in symptoms as compared with placebo.” The editorialist goes on the say that the PLEASE trial has a “simple message… Patients with subjective, vexing symptoms attributed to Lyme disease should not anticipate that even longer courses of antibiotics will produce relief.”
Despite the clear cut findings and the consistency of the results with prior studies, the persistent infection theory continues unabated. This is evident by the demands and expectations of patient advocates attending the federal framework on Lyme disease held in Ottawa in the spring of 2016. (2) Nevertheless, I agree with the title of the NEJM editorial: “Time for a Different Approach to Lyme Disease and Long-Term Symptoms.”
What I do now
So what should that approach be? Patients with symptoms attributed to CLD fall into 3 categories:
- Post-Treatment Lyme Syndrome: Past infection with Lyme but no evidence of persistent infection.
- Alternatively Diagnosed CLD: False positive testing by non-reference lab and no evidence of ever having been infected.
- Clinical Diagnosed CLD: Based on symptoms only with no positive serology; diagnosis usually made by naturopath.
Regardless of the category, the vast majority of these patients have non-specific symptoms of fatigue, pain, sleep disturbance, and unexplained symptoms. They all have CSS, usually CFS or FM. Many have additional CSS including irritable bowel syndrome, migraines, temporomandibular disorder, or others. There is no current cure for these conditions, though many things can help. Clinicians can access CCDP protocols on sleep, CFS, and FM, as well as other many other resources. (17) They can direct patients to CCDP’s comprehensive online library of patient resources: view (18), summarized in the following handout: view. (19) Patients may also be referred to the Complex Chronic Diseases Program (CCDP) at Women’s Hospital: referral form. (20) I would encourage clinicians to continue supporting referred patients using the resources listed above while they await assessment by the CCDP. Wait times can be around 2 years.
The main barriers to caring for patients with symptoms attributed to CLD are the tenacious commitment to the concept of persistent infection and the demands for long-term antibiotics by many of them. It is important not to get involved in arguments around contested causation and to remember that they suffer debilitating symptoms and disability.
References & Resources:
- UpToDate. 2016. (View)
- Conference to develop a federal framework on Lyme disease, May 15 to 17, 2016. Mandated by the Federal Framework on Lyme Disease Act. Updated October 26, 2016. (View)
- Rich P. TICKS! on the march. Sidebar The lowdown on Lyme disease. Medical Post [serial online]. 2016;52:9. (Request from CPSBC or view UBC) DOI:1176/appi.neuropsych.12090223 http://www.canadianhealthcarenetwork.ca/physicians/magazines/the-medical-post/june-21-2016
- Ric Arseneau. Hope for patients with fatigue, pain, and unexplained symptoms. This Changed My Practice. Published October 13, 2015. Accessed October 26, 2016. (View)
- Ric Arseneau. Chronic Fatigue Syndrome Upgraded to Disease. This Changed My Practice. Published November 30, 2016. Accessed November 30, 2016. (View)
- Batheja S, Nields JA, Landa A, Fallon BA. Post-Treatment Lyme Syndrome and Central Sensitization. The Journal of Neuropsychiatry and Clinical Neurosciences. 2013;25:176-186. (Request from CPSBC or view UBC) DOI:1176/appi.neuropsych.12090223.
- Patrick D, Miller R, Gardy J, et al. Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome. Clinical Infectious Diseases. 2015;61:1084-1091. (Request from CPSBC or view UBC) DOI: 10.1093/cid/civ470.
- Fleming KC, Volcheck MM. Central sensitization syndrome and the initial evaluation of a patient with fibromyalgia: a review. Rambam Maimonides medical journal. 2015;6:e0020. (View) DOI: 10.5041/RMMJ.10204.
- Henry P, Morshed M. Lyme disease in British Columbia: are we really missing an epidemic? BC Medical Journal. 2011;53;224-229. (View)
- The Public Health Evidence for FDA Oversight of Laboratory Developed Tests: 20 Case Studies. Office of Public Health Strategy and Analysis; Office of the Commissioner; Food and Drug Administration. November 16, 2015. (View)
- Physician Handout: BC Women’s Hospital+ Health Centre. Laboratory Diagnosis of Lyme Disease: Fact Sheet. Updated March 14, 2016. (View)
- Halperin JJ. Chronic Lyme disease: misconceptions and challenges for patient management. Infection and drug resistance. 2015. (View) DOI: 10.2147/IDR.S66739.
- Arseneau. St. Paul’s Hospital Grand Rounds presentation. Lyme Disease Controversies and Misconceptions: April 2016 (View)
- Berende A, ter Hofstede H, Vos F, 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. New England Journal of Medicine. 2014 Oct 16;14:543. (View) DOI:1186/s12879-014-0543-y.
- Berende A, ter Hofstede H, Vos F, et al. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. New England Journal of Medicine. 2016;374:1209-1220. (Request from CPSBC or view UBC) DOI: 10.1056/NEJMoa1505425.
- Melia M, Auwaerter P. Time for a Different Approach to Lyme Disease and Long-Term Symptoms. New England Journal of Medicine. 2016;374:1277-1278. (View) DOI: 10.1056/NEJMe1502350.
- Physician Handout: Clinician Resources: BC Women’s Hospital+ Health Centre. Complex Chronic Disease. (View) http://www.bcwomens.ca/health-professionals/professional-resources/complex-chronic-disease
- Patient Handout: BC Women’s Hospital+ Health Centre. Living with Complex Chronic Disease. (View) http://www.bcwomens.ca/health-info/living-with-illness/living-with-complex-chronic-disease
- Patient Handout: Complex Chronic Diseases Program Resources: Chronic Lyme Like Syndrome. Accessed December 10, 2016. (View) https://med-fom-tcmp.sites.olt.ubc.ca/files/2016/11/TCMP-2016-11-24-Areseneau-CLLS-Resources.pdf
- Physician Handout: Refer a patient: BC Women’s Hospital+ Health Centre. Complex Chronic Diseases (ME/CFS, FM, CDL,MCS). (View) http://www.bcwomens.ca/health-professionals/refer-a-patient/complex-chronic-diseases-program
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Wow thanks for this most useful review!!! Here in the Kootenays I sometimes feel at the epicentre of chronic Lyme sufferers…….especially as we have a physician offering “more sensitive” testing at non validated US labs with frequent positive results. I have seen 13 year olds given a year of rifampin for diagnoses of concurrent Lyme, Babesiosis and Ehrlichosis. It is good to have more resources to offer(often desperate) patients, most of whom probably fit CSS criteria. Are there any trials of mindfulness to assist in calming that overly sensitized nervous system?
In Kelowna as soon as the weather warms and the ticks start coming in to the ED usually attached to a young child I have to relook at whether recommendations have changed. I continually am reassured that the presence of Lyme disease is low but still potentially present. Instead of going on the defence I have started to encouraged parents to send the tick in with a phsyician’s help.
How to submit a tick for testing
If your doctor wants to have the tick tested:
Save the tick in a container with a tight fitting top.
Dampen a small cotton ball and put it into the tick container to keep the tick alive. (A live tick is necessary for culturing the spirochete which causes Lyme disease.)
Label the container with date shipped, name and address of person bitten or what type of animal the tick was from, what part of the body was bitten, and what part of the province the tick probably came from. Also include the name and address of your physician.
Testing is only available for BC residents.
Ticks must be submitted as soon as possible by a physician or public health professional to:
BC Public Health Microbiology and Reference Laboratory
Parasitology
655 West 12th Ave.
Vancouver V5Z 4R4 BC Canada
Atleast when it comes back as a non carrying type or negative it provides some piece of mind. Educating what to watch for is also useful, at least from a medicolegal point. A review on testing is available in BCMJ Vol 57, No 9 , Nov 2015
Do you prescribe longer term antibiotics when the patient requests them, even after the explanation of their non-utility is given? If so, what rationale do you provide; if not, how do the patients respond?
Thank you for this. What an excellent review and update.
Another excellent article by DR Arsenault. Biomechanical medicine often lacks the imagination to reconceptualise different kinds of illness. Thank you for the resources and encouragement to take the time to educate this often exploited and harmed group of patients.Info on low prevalence of infected ticks will help my educational endeavors.
Rick Hudson MD CCFP
Thoughtful straightforward article which helps sort out true Lyme from imagined Lyme disease and points on how to manage both patient populations. Thank you Carol Pfefferkorn, M.D.
Although not directly my area of practice, which is Child and Adolescent Psychiatry, the topic of Lyme disease being the root of a presentation such as OCD or other non-specific symptoms has come up in my practice. I appreciate the note on the high rates of false positives given by certain labs in the US. I also appreciate the discussion on the complexity of these issues and how we don’t always have answers for our patients but we might have some solutions.
Fantastic re-framing and great advice about not getting into a debate about causation. There will be a subset of patients who still want eternal ceftriaxone who will balk, but even then hopefully a seed can be planted for the future.
Response to questions:
There is moderated evidence that mindfulness based practices help “calm” the adrenergic symptoms associated with Central Sensitivity Syndromes. We use these at the Complex Chronic Disease Program, and I use them in my practice.
The fact that there is no evidence of persistent infections in patients with symptoms attributed to “Chronic Lyme Disease,” does not mean that we do not need to be vigilant for Lyme disease itself. Tick surveillance is very important, and I strongly agree with the recommendations made by Dr. Gord McInnes above. Early treatment of acute Lyme disease is important in preventing late Lyme disease (e.g., arthritis).
I do not prescribe antibiotics (or antifungals) for symptoms attributed to “chronic Lyme disease”. In patients who are positive for Lyme by BCCDC testing and have not been treated in the past, a short- course of antibiotics are warranted. In my discussions with patients, I sense how committed they are to the concept of CLD and how open they are to alternative explanations (e.g., CSS, ME/CFS, FM). If I sense any resistance, I stop focusing on an alternative explanation and talk about competing theories for the symptoms – CLD vs CSS. I tell patients that while I cannot prescribe antibiotics given the lack of evidence regarding benefit and the well know significant morbidity, I am happy to work with them on other approaches to their symptoms. I provide them with a copy of an article that looks at both the persistent infection vs triggering of CSS:
https://drive.google.com/open?id=0B7bF4u582CXSRjVTQnBIQjFsV2c
Despite this, it is not uncommon for me to encounter patients unwilling to consider anything else but the concept of CLD.
Thank you for the kind responses.
Tick can be tested in asymptomatic patients: For more info:
http://www.bccdc.ca/health-info/diseases-conditions/lyme-disease-borrelia-burgdorferi-infection#TickRemoval
This ever-timely area is so eruditely presented here, & is much appreciated. Most patients have had many courses of antibiotics & various other medications, & still have persistent symptoms. The VLsE1 test would seem our greatest asset in separating fact from perceived CLD with symptoms, & this non-confrontational approach to the suffering patient will surely bring comfort as well as safer treatment programs.