It is a more common question than you might think. And, people are sometimes confused about what Lyme disease is. This is common with most medical conditions. Medicine is complicated. Without training and a lengthy, diligent effort, one can only have an incomplete understanding, and it will be easy to confuse the facts. Even with training we are left with many questions in science and medicine. That is probably true of any complex issue. This is where logic is needed and the scientific method is crucial. Science is still the best tool we have for trying to solve these difficult questions. When it comes to treating illness, one should learn about the disease in order “to know what you don’t know,” because the opposite situation is dangerous.
I will attempt to explain Lyme as we know it, and answer the question as to whether there is a connection with PD so that there is hopefully less confusion, and perhaps some clarity. This will be somewhat of long article for MPDN, in part because it is complicated, and in part because I am aware that even mentioning the topic of Lyme may upset some patients who have accepted a diagnosis or seem to believe that there is some effort to suppress information about Lyme disease. It is for some, a touchy subject. Still, because it keeps coming up, because it can be a very serious illness, and because the season for Lyme has come along, I want to try to address the issues that have been raised in my office. The best that I can offer is to carefully take points apart, and through this, I hope I can dispel false ideas and bring us closer to understanding this subject.
Why is Lyme a problem?
Lyme disease is on the rise in New England, and can cause serious illness, sometimes affecting the nervous system. The majority of infections are straightforward, and treatment is usually simple. However, diagnosis can sometimes be tricky, especially early after exposure, when the screening test is less accurate. There are, from time to time, complicated cases (such as when one has been untreated for a long duration), but antibiotics appear to be effective, even in that situation. As we will see below, most confusion arises around the post-treatment if patients have persistent symptoms. Some patients incorrectly interpret ongoing symptoms as an ongoing infection, and conclude that mainstream medicine is not the way to deal with diagnosis or treatment. That feeling is not limited to Lyme disease, as we live in a time of open anti-science sentiment and distrust of medicine, even in our elected officials. Out of this fringe, certain jargon has arisen around Lyme disease, reflecting confusion and misunderstanding. Examples include the terms “chronic Lyme,” “Lyme flare,” and “Lyme-literate doctor.” I will discuss the first two terms below. “Lyme-literate,” it is worth pointing out here, actually refers to a healthcare practitioner who accepts and uses alternative, unproven concepts and treatments. The terms listed above are not accepted by most neurologists, infectious disease doctors, or scientists who study Lyme. The language may still be spread by the occasional healthcare provider who does not accept or follow scientifically and evidence-based guidelines, or more commonly by patients who believe they are chronically infected by the organism that causes Lyme disease. Patient advocate groups have arisen and Lyme has become a political issue in New England. As we will see below, laws have been passed regarding Lyme which may be counter to medical guidelines. All of this may lead to confusion and distrust among patients who feel caught in the middle. So, what are the facts? How can we understand Lyme? Can we have some clarity about this disease?
In the beginning
Lyme disease in the U.S. is named for the small coastal Connecticut town where clusters of cases were first reported in 1975. The condition has spread over time, and in 2017 Lyme is found only rarely outside of the Northeast, mid-Atlantic, and
upper Midwest states. Lyme is caused by infection with Borrelia burgdorferi, a bacterium transmitted to humans though bite of an infected deer tick (Ixodes scapularis). Deer ticks are black-legged, and smaller than the more common dog ticks (1).
In Maine, deer ticks tend to cluster in southern and mid coastal regions, probably because of the warmer temperatures, the abundance of mice (which thrive near people and also host deer ticks), and the abundance of deer. It is still possible to catch Lyme disease in any part of the state, though cases are much rarer in western and northern regions where temperatures are lower and mice are probably less abundant (2).
Signs and symptoms of Lyme
Some patients with Lyme disease will have an expanding, and sometimes bullseye-shaped rash, called erythema migrans (EM),
which may occur in about half of patients any time between 3 and 30 days after a tick bite. In 2003, when Lyme was not as common, or as well known, a study published in the New England Journal of Medicine (NEJM) (3) screened 10,936 people from 10 states where Lyme was endemic over a 20 month period in an attempt to identify all infections of Lyme, and to describe presenting symptoms. Ultimately, 201 confirmed cases were found. Frequent early symptoms of Lyme disease in the NEJM paper included EM, fever, headache, migratory joint pains, muscle pains, fatigue, and palpitations. The authors noted only 2 to 3 percent of the patients had later systemic involvement such as facial palsy, trigeminal neuropathy, or Lyme arthritis. These are issues that tend to arise only if treatment is delayed (though I would insert that I have seen facial palsy as the presenting symptom). Over time we have learned that another, albeit uncommon late sign of untreated Lyme is carditis (inflammation of the heart) causing AV block, which affects the rhythm of the heartbeat. Further, Lyme as a cause of meningitis (inflammation of the protective tissue covering the brain and spinal cord) is also rare in the U.S. Lyme is a reportable illness in Maine, meaning that doctors and labs are required to report cases to the Maine Centers for Disease Control (CDC). *see Footnote
Maine CDC investigates all reports of positive laboratory tests or clinical diagnoses of EM. Maine CDC also is compelled to produce a formal report for the State Legislature, who as shown below, has been interested in Lyme disease for several years (4).
From the report, we know that Lyme is on the rise, and in 2015 (the latest data publicly available at the time of this article) there were 1,171 “confirmed and probable” cases by federal CDC criteria (5). Among those cases, EM was present 51%, arthritis in 30%, Bell’s palsy or other peripheral cranial neuritis (infection of nerves of the face and head) in 10%. Hospitalization occurred in 3% of cases (38 total). There was no mention of meningitis or other neurologic illness in the report, except to say that these conditions are rare. There were no reports of parkinsonism.
So why do some people think PD is related to Lyme?
To be clear, most people don’t. Onset of PD during a Lyme infection is not common, and there is no evidence that Lyme will cause PD. Still, I am frequently asked by patients with new symptoms of parkinsonism to test for Lyme, if it could be Lyme, or some variation on that theme, and I am not sure why. Further, there are some patients who have been convinced that Lyme disease caused the parkinsonism they began to experience during or some time after a Lyme infection (whether or not they actually had an infection). It is often difficult to convince someone otherwise when the two conditions seemed to come together.
However, one should remember that correlation does not equal causation: two events may occur at the same time and have nothing to do with one another.
Alternatively, there may be a relationship of a sort, but it is not intuitive. Trauma or systemic illness may unmask early PD. Think of it like this: the brain will often compensate for neurologic disease and it may be some time before you know there is a problem as it is slowly smoldering along. Physicians refer to this as the “prodrome.” The progressive loss of dopamine people with PD experience usually takes a minimum of 6 to 7 years to become severe enough to cause visible signs of disease such as tremor, stiffness, or slowness. And, many conditions such as illnesses, surgeries, and traumas may stress the brain and body of a person on the verge of showing signs of PD. Perhaps that stress also uses up dopamine. Whatever the case, that person may then finally start to notice the early indications of parkinsonism that would have occurred in due time, but have become evident sooner. PD is not unique in this way. Several neurologic diseases become apparent a little sooner than they would have in the setting of some other illness. When this happens patients may incorrectly assume one problem caused the other. In fact, one author noted (5):
“Virtually every known neurologic disorder has been blamed on this infection. For most (multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease), evidence is scant, nonexistent, or coincidental.”
I can see why people might think there is a connection, and it is a very human trait to look for patterns and associations. We are essentially hard-wired that way. It is good idea for survival to remember dangerous correlations. The flaw is that they don’t always connect. We should reason through seemingly connected problems to see if there is a false lead.
The issue is further complicated as Lyme is a complex area in medicine. There is a great deal known about Lyme in science, but much of it is not straightforward, and requires some medical knowledge. There is ongoing research, and like any area of science, there is room for an elevated understanding. People outside of medicine who are trying to learn about Lyme should be careful what sources are used. There is unfortunately an excess amount of false and misleading information on the internet about Lyme. There are also legitimate sources, such as the CDC.
How do you test for Lyme?
The CDC recommends a two-step laboratory testing process. When Lyme is suspected, the first step is an enzyme-immunoassay (EIA). Physicians may also choose the less commonly used indirect immunofluorescence assay (IFA).
If the first step is negative, no additional step is recommended. However, the test checks for antibodies against Lyme which may not have developed in early disease, and may take as long as 8 weeks to develop. Therefore, the EIA test may be falsely negative about 32% of the time in early disease. Repeat testing is sometimes necessary, and often patients are treated empirically if clinical suspicion is high. Doctors should also consider alternative diagnoses, such as other tick-borne illnesses.
If the first step is positive or equivocal, this may mean that similar antibodies are detected, but not necessarily those against Lyme. Thus, the second step is an immunoblot test called a Western blot, a confirmatory test. Results are interpreted as positive only when both steps of the testing are positive. The CDC does not recommend skipping the first step.
There are other commercial lab tests available which are not approved by the FDA or the CDC, yet are still used by a minority of medical practitioners in Maine.
When unproven tests are used, the diagnosis is suspect at best, leaving the actual cause of suffering undiagnosed and untreated.
How is Lyme treated?
Treatment of Lyme disease in most cases is with the oral antibiotic doxycycline for 2 to 4 weeks. Antibiotics kill bacteria. The bacteria that causes Lyme disease is highly susceptible to the drug and a single round of antibiotics is curative in the majority of cases. Infrequently, IV antibiotics such as ceftriaxone are used, such as when a patient has been left untreated for some time and there is evidence of spread in the body.
What is the story with “chronic Lyme?”
About 10% of patients treated for Lyme disease with a recommended course of antibiotics will report ongoing symptoms of fatigue, pain, or joint and muscle aches (6,7). This is unlikely to be an ongoing infection. Most of these residual symptoms resolve after six months, though an even smaller number of patients will report persistent symptoms. Patients, and some health care providers have occasionally referred to this syndrome as “chronic Lyme disease,” which is inaccurate, and the term has been rejected by experts (8).
This is not to say there is no condition. After bacteria are eradicated with antibiotics, if there is a residual condition as described here, it is known by the CDC as “Post-treatment Lyme Disease Syndrome” (PTLDS) (9).
Per the CDC many medical experts attribute lingering symptoms to tissue damage and probable activation of the immune system that occurred during the infection, producing what is called an autoimmune response, in which the immune system later attacks the body. This would not be a unique phenomenon. Examples of other infections that might cause persistent complications and autoimmune response include the bacteria Campylobacter jejuni, with resulting Guillain-Barre syndrome, or bacterial strep throat, resulting in Scarlet fever and later rheumatic heart disease. These are not chronic infections, but the result of the immune system being essentially confused by the original bacteria into attacking some part of the body, even long after the infection is gone. This is an area of medicine in which doctors of immunology and rheumatology are experts. They, along with the boards of neurology and infectious disease, do not recognize “chronic Lyme disease.”
Still, there do not seem to be satisfying treatments for many of the symptoms of PTLDS, and patients may understandably feel very frustrated and suspicious. Adding to the confusion, there are some health care providers who do not follow the guidelines and explain chronic symptoms as being due to chronic infection with Borrelia burgdorferi. I have heard from several Mainers over the last decade of how they have been given either very long, or repeated courses of antibiotics and other treatments (some of which are not FDA approved for any condition) to treat what they refer to as “Lyme flares.” Unless active infection is detected, antibiotics are not indicated, not helpful, and may be harmful to the patient and to others (10-15).
What’s the harm in taking extra antibiotics?
One way unnecessary antibiotics are harmful is through drug resistance. There are over 1,000 species of bacteria in the human gut, and many species in the upper respiratory system. We have more bacteria than you may think. There are more of them in us that there are cells in our own bodies. If that is hard to fathom, consider that their cells tend to be much smaller than ours.
Though most bacteria we possess are benign or even helpful to us, we may harbor bacteria that can turn against us if the conditions are right. And, if exposed to antibiotics, many species of bacteria are able develop drug resistance which may lead to infections that we cannot treat with medications that would have otherwise been curative (12).
Thus, a person may unwittingly develop drug resistant bacteria that may attack then, or lay in waiting for later. In either case, the results can be deadly. Drug-resistant bacteria, and there are some very scary ones, can directly affect the person taking the medication, and can also spread to others.
Antibiotics are not completely benign or risk-free. People may have side effects which can be serious, and death due to treatment for Lyme has been reported (15, 23). Between 2001 and 2014 the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), funded four placebo-controlled clinical studies evaluating whether or not giving prolonged courses of antibiotics to patients with persistent symptoms was helpful (16). The studies were well-designed, and published in peer-reviewed journals after rigorous statistical and scientific review (17-20). Specifically, studies evaluated:
- whether B. burgdorferi was susceptible to the antibiotics used;
- whether antibiotics remain at effective levels throughout the course of treatment;
- whether antibiotics cross the blood-brain barrier to reach the brain and central nervous system;
- whether the antibiotics kill bacteria living outside or inside cells of mammals;
- safety and welfare of patients enrolled in the trials.
The bottom line was that prolonged antibiotic use was not recommended due to lack of efficacy and the risks of antibiotic therapy. Side effects were common and included intravenous line infections, blood clots, allergic reactions, and gall bladder removal.
Is there a link with Lyme and PD?
There is very little in medical literature linking Lyme to parkinsonism. In a review of the online NIH database Pubmed, which extends back decades and covers peer-reviewed medical journals in English and some foreign languages, there are very few reports of any possible association. In 1989, 12 cases of Lyme disease with neurologic complications were reported in a review of available data (21). Meningoradiculitis (infection of the protective covering of the brain and spinal cord) was seen in seven patients; facial palsy in two cases; infection of the end of the spinal cord, the cauda equina, was seen in one case; and inflammation of the spinal cord and its covering (meningomyelitis) was seen in two. Severe pain was a prominent feature in most cases, and this “consistently and rapidly” improved on high-dose intravenous penicillin, while paresthesias or fatigue often lasted several months, suggestive of the later-described post-treatment syndrome. In a patient who already had parkinsonism, the neurologic condition was not changed by the infection or the antibiotic.
A case which is sometimes cited was a 1997 report of a 78 year old man in Spain with sub-acute mental deterioration, and progressive supranuclear palsy (PSP) presentation (22). PSP is a form of atypical parkinsonism, which is not PD, and is caused by a completely different mechanism in the brain. While there may be some features that are similar to PD, PSP has distinct features: severe eye movement problems, very early falls, early and advanced stiffness of the spine, rather than the limbs. In this patient, Lyme tested positive in the blood and cerebrospinal fluid. The patient reportedly improved after treatment with ceftriaxone. However, this single case report is in question as no organism was found in the brain, and no later follow up as to whether the patient developed parkinsonism was given. Case reports in the medical literature are a description of an unusual situation. Many are written to simply call attention to a possible phenomenon. They are not proof of concept. If no more cases are reported, the association is either extremely rare, or nonexistent. As far as I can tell, no other compelling cases have been described in the literature. There is simply is not adequate evidence to suggest a link between PD and Lyme.
Is Lyme a political issue?
Though Lyme disease is complicated, there is a great deal more known than I have covered here. Obviously, keeping track of the intricate data is not simple. There are guidelines by the CDC, the American Academy of Neurology, and the Infectious Disease Society of America. And there are regulatory agencies in our state: the Maine CDC, the Maine Board of Licensure in Medicine, and the Maine Medical Association. Yet, the legislature of the State of Maine has weighed in contrary to guidelines on Lyme disease.
In 2013 “An Act to Inform Persons for the Options of Treating Lyme Disease” (23) recognized PTLDS, but confused the issue by stating “There are some doctors who believe that longer doses of antibiotics may sometimes be helpful.” One familiar with science will immediately recognize the problems with this statement. The first issue is that it promotes the idea of chronic infection, which is not supported by medical evidence. The second problem is in the terminology. Belief is not science. Belief is akin to faith, acceptance of an idea in the absence of evidence, or in spite of evidence disproving the idea. Doctors are not trained to follow belief. Doctors and other scientists are trained to use logic and the scientific method to question, test, and interpret nature. Through rigorous testing, studies, peer-reviewed publication, and the skills of critical analysis, doctors evaluate the available data to arrive at an understanding of disease. Guidelines are the product of consensus among a designated panel of experts in a field after very careful consideration of the data. Guidelines are meant to protect people and offer the best possible, and safest approach. When the Maine Board of Licensure takes action against a doctor who does not follow guidelines, it is to protect patients.
The law further required the Maine CDC website to list “different alternatives for treatment” instead of simply stating that the evidence-based, expert consensus-driven, peer-reviewed CDC guidelines should be followed. The federal CDC has described some alternatives to therapy (24) as a caution, and noted that none of these are proven helpful, and some are dangerous:
“Patients given a diagnosis of chronic Lyme disease have been prescribed various treatments for which there is often no evidence of effectiveness, including extended courses of antibiotics (lasting months to years), IV infusions of hydrogen peroxide, immunoglobulin therapy, hyperbaric oxygen therapy, electromagnetic frequency treatments, garlic supplements, colloidal silver, and stem cell transplants.”
The state was not finished with Lyme however. In 2015 “An Act to Improve Treatments for Lyme Disease” (25) was passed in Maine, indicating that physicians may prescribe long-term antibiotic therapy against Lyme, thus blocking the Maine Board of Licensure in Medicine from taking action against doctors who treat patients outside of the guidelines for this condition. In June 2015, the Portland Press Herald ran an article about the law, “Maine Legislature clears way for long-term Lyme disease treatment,” (26), in which patients who believed they had chronic Lyme disease gave positive statements in support of the new legislation. However, Dr. Phillip Baker, executive director of the American Lyme Disease Foundation, was quoted to say the law was counterproductive, and it was “sad and most unfortunate that this bill was passed.” He cited the above four NIH studies proving extended antibiotic therapy was not beneficial to patients and may instead be harmful. He noted:
“To ignore such evidence to promote an unproven, unsafe therapeutic approach cannot be in the best interests of the public health and the citizens of Maine.”
Less restraint was voiced by an online blogger for the Society for Science-Based Medicine (27), who reacted to the 2015 Maine law and noted regarding chronic Lyme:
“A whole health care cottage industry has grown up around this fictitious diagnosis, which includes, in addition to physicians, various alternative medicine practitioners, and labs which use unconventional tests to sell the patient on the diagnosis. Having dispensed with the need for objective testing and firm diagnostic criteria, a capacious range of symptoms is a ready rationale for all manner of CAM treatments, such as herbs, supplements, homeopathy, cranial sacral therapy, and such. The favored medical treatment for “chronic” Lyme is long-term antibiotic therapy, an odd choice in the normally pharmaceutically adverse pseudoscience universe.”
Finally, June 16, 2017 the CDC Morbidity and Mortality Weekly Report (MMWR) “Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease — United States” described five patients, one of whom died from the treatment, and others who experienced serious infections after unnecessary treatment with antibiotics. In one case a fatal neurologic diagnosis unrelated to Lyme was missed.
Summary
- Lyme disease can be a serious illness.
- Proper diagnosis and treatment should be sought (following guidelines).
- There is no known connection between Lyme disease and PD.
- Chronic Lyme disease is a term that is not accepted by the CDC, which has instead noted that after bacteria are eradicated with antibiotics, if there is a residual condition as described above, it is known as “Post-treatment Lyme Disease Syndrome” (PTLDS).
*Footnote:
Federal CDC defines cases for reporting as “confirmed,” “probable,” or “suspect,” (5) when a person has certain of the following:
1) EM or
2) at least one disseminated manifestation and laboratory confirmation of one of the following:
- Positive culture for B. burgdorferi
- IgG positive Western blot
- Positive ELISA test and an IgM positive Western blot within 30 days of onset (and confirmed by IgG Western blot)
- CSF antibody positive by EIA or IFA, when the titer is higher than in serum
Probable cases must meet one of the laboratory criteria mentioned above and be physician diagnosed.
REFERENCES
- https://extension.umaine.edu/ipm/tickid/maine-tick-species/deer-tick-or-black-legged-tick/
- http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/lyme/documents/deer-tick-map-2013.pdf
- The Presenting Manifestations of Lyme Disease and the Outcomes of Treatment. N Engl J Med 2003; 348:2472-2474, June 12, 2003.
- http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/lyme/documents/Lyme-Legislative-Report-2016.pdf
- https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2011/
- 20. Halperin J. Nervous systme Lyme disease: is there a controversy? Semin Neurol. 2011 Jul;31(3):317-24.
- Feder et al., A critical appraisal of “chronic Lyme disease”. N Engl J Med 2007; 357: 1422-1430
- Scieszka et al., Post-Lyme disease syndrome. Reumatologia. 2015;53(1):46-8.
- https://www.cdc.gov/lyme/postlds/index.html
- De Wild, et al., Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of ‘chronic Lyme disease’. Acta Clin Belg. 2016 May 12:1-5. [Epub ahead of print]
- Ettestad, et al, Biliary complications in the treatment of unsubstantiated Lyme disease. J Infect Dis. 1995;171:356–361.
- Holzbauer, et al. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. ClinInfect Dis. 2010;51:369–370.
- Lantos, et al. Unorthodox alternative therapies marketed to treat Lyme disease. Clin Infect Dis. 2015 Jun 15;60(12):1776-82.
- Marks, et al. Antibiotic treatment for chronic Lyme disease-Say no to the DRESS. JAMA Intern Med. 2016 Dec 1;176(12):1745-1746.
- Patel, et al., Death from inappropriate therapy for Lyme disease. Clin Infect Dis. 2000;31(4):1107-9.
- https://www.cdc.gov/lyme/treatment/prolonged/index.html
- Berende 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 Oct 16;14:543
- Klempner, et al., Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. New Eng. J. Med.2001;(345):85-92
- Krupp, et al, Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003 Jun 24;60(12):1923-30.
- Fallon, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008 Mar 25;70(13):992-1003.
21..Viader et al, Neurologic forms of Lyme disease. 12 cases. Rev Neurol.1989;145(5):362-8.
- Garcia-Moreno, et al. Neuroborreliosis in a patient with progressive supranuclear paralysis. An association or the cause?. Rev Neurol. 1997 Dec;25(148):1919-
- CDC Morbidity and Mortality Weekly Report (MMWR) “Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease — United States” online at https://www.cdc.gov/mmwr/volumes/66/wr/mm6623a3.htm
- https://legislature.maine.gov/bills/getPDF.asp?paper=HP0416&item=1&snum=126
- http://www.mainelegislature.org/legis/bills/getPDF.asp?paper=HP0289&item=4&snum=127
- http://www.pressherald.com/2015/06/29/maine-legislature-clears-way-for-long-term-lyme-disease-treatment/
27. http://sfsbm.org/index.php?option=com_easyblog&view=entry&id=666
