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Your Comprehensive Guide to Lyme Disease

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Lyme disease is becoming increasingly common in the United States and worldwide. Find out more about what causes Lyme, symptoms of an acute or chronic infection, and how the Functional Medicine approach can help treat the condition.

Lyme Disease
Lyme disease is becoming a serious problem across the United States. iStock/zilli

Lyme disease is exploding in prevalence both in the United States and around the world. While the CDC reports that approximately 300,000 people are diagnosed with Lyme disease each year, this number may underestimate the true prevalence of the disease due to faulty diagnostic testing, misdiagnosis, and underreporting. (1) Read on to learn about the latest research on Lyme disease and why it is urgent that we increase awareness of this severe, rapidly growing problem.

What Is Lyme Disease?

Lyme disease is a multisystem infectious disease caused by the bacterium Borrelia burgdorferi and transmitted to humans through the bite of infected ticks. In the United States, two types of ticks carry Lyme disease:

  • The Eastern blacklegged tick (Ixodes scapularis), also known as the deer tick, transmits Lyme disease on the East Coast and in the Midwest
  • The Western blacklegged tick (Ixodes pacificus) transmits the disease on the West Coast

A third type of tick, the lone star tick (Amblyomma americanum), has not been found to transmit Lyme disease but does transmit other harmful pathogens. Its rapid geographic expansion into Lyme-endemic territories, including the Southeast, East Coast, and Midwest, is a significant cause for concern because the pathogens it carries can worsen illness in Lyme-infected individuals. (2)

Long misunderstood, Lyme disease is becoming increasingly common and dangerous across the United States. Find out more about how this disease is transmitted, the symptoms it causes, and how to get tested. #functionalmedicine #chriskresser

What Causes Lyme Disease: Borrelia burgdorferi

Borrelia burgdorferi is a spirochete, a spiral-shaped bacterium, related to the bacteria that cause syphilis but more genetically complex. It is the primary causative agent of Lyme disease in North America, whereas Borrelia afzelii and Borrelia garinii, other members of the Borrelia species complex, are the primary causes of Lyme infection in Europe and Asia. (3) More recently in North America, Borrelia miyamotoi, Borrelia mayonii, and Borrelia hermsii have also been implicated in a significant proportion of Lyme disease cases. (4, 5, 6, 7)

How Is Lyme Disease Transmitted?

Borrelia bacteria require both an invertebrate vector—namely, ticks of the Ixodes genus—and a vertebrate host to successfully complete their life cycle. Ticks are vehicles for transmitting Borrelia to “reservoir hosts,” including mice and deer, which typically don’t experience ill effects from the pathogen.

Humans, while not vehicles for Borrelia transmission, serve a different but equally critical role: We are a source of blood for feeding ticks, thus serving a fundamental role in Borrelia’s life cycle.

Throughout their approximately three-year lifespan, ticks go through four life stages: egg, larva, nymph, and adult. Nymph Eastern blacklegged ticks have the highest Lyme disease infection rate, whereas lone star ticks attack human hosts aggressively in all life stages—adult, nymph, and larvae. (8)

Ticks transmit Borrelia burgdorferi (and many other pathogens) during the feeding process:

  • First, a tick must find a feeding spot. Once it lands on a human or animal, it attaches to the skin and secretes a numbing agent that prevents the host from feeling the tick bite.
  • Next, the tick bites into the surface of the skin, inserting a feeding tube and secreting a cement-like substance that firmly attaches it to the skin during the blood meal.
  • The tick slowly sucks blood from the host over several days before dropping off and preparing for a new life stage.

If the tick contains any pathogens, the infectious organisms within its saliva are transmitted to the host during the feeding process.

History of Lyme Disease

Early case reports of Lyme disease began to emerge in the United States in the late 1960s and 1970s. However, the medical community did not take a serious interest in the condition until 1975, when a group of people in the Connecticut towns of Lyme and Old Lyme came down with an odd assortment of symptoms, including fatigue, arthritis, and neurological dysfunction.

The scientific and medical communities’ investigations ultimately led them to discover that all afflicted patients had experienced tick bites before the onset of illness. Eventually, the blacklegged tick was implicated in the transmission of the newfound disease, which became known as Lyme disease. In 1981, Swiss-American scientist Willy Burgdorfer discovered the infectious cause of Lyme disease, a hardy, genetically complex spirochete, which he named Borrelia burgdorferi. (9)

Lyme disease, once considered a rare condition, has exploded in prevalence over the past several decades. According to the authors of a recent peer-reviewed article on Lyme, “Lyme disease should be recognized as a virulent epidemic that is at least six times more common than HIV/AIDS.” (10)

Lyme Disease: A Controversial Illness

Since its discovery, Lyme disease has been steeped in controversy. The mainstream medical community claims that Lyme disease is rare and easily treated with a single round of antibiotics. While supporters of this claim include several highly esteemed medical organizations, including the CDC and the Infectious Diseases Society of America (IDSA), serious doubts have been expressed about the ethical behavior of these groups in their development of Lyme disease treatment guidelines. (11)

The International Lyme and Associated Diseases Society (ILADS) stands in direct opposition to the CDC and IDSA, arguing that Lyme disease is a complex condition that often requires extended treatment beyond what the conventional guidelines recommend. Despite abundant evidence that Lyme disease persists after treatment and that current diagnostic tests are inadequate, the CDC and IDSA continue to resist changing screening and treatment guidelines. Their actions (or lack thereof) on the Lyme front continue to deprive patients of the tests and treatment they need to get better.

What Are the Symptoms of Lyme Disease?

Once an infected tick bites a human, it begins to transmit microbes, among which Borrelia burgdorferi may be included. If the immune system responds immediately to the influx of B. burgdorferi, acute symptoms occur. If the immune system does not quickly detect the bacteria, or if treatments during the acute phase fail, Lyme disease may produce chronic symptoms.

Acute Lyme Disease Symptoms

Two of the most well-recognized events that point towards a Lyme disease diagnosis are a recent tick bite or an erythema migrans lesion, also known as a “bull’s-eye” rash.

An erythema migrans is specific for Lyme disease; people with it can receive a diagnosis without clinical testing. However, few people with Lyme disease recall a prior tick bite and, in up to 30 percent of cases, an erythema migrans doesn’t appear, severely limiting the clinical utility of these two diagnostic features. (12)

Other symptoms of acute Lyme disease include:

  • Headache
  • Fatigue
  • Rash
  • Night and day sweats
  • Chills
  • Muscle pain
  • Joint pain
  • Neck pain
  • Sleep issues

However, even these symptoms are frequently mistaken for other illnesses, such as the flu, delaying Lyme disease diagnosis.

Chronic Lyme Disease Symptoms

Lyme disease can become chronic, causing significant physical and mental impairment. Chronic Lyme disease is estimated to afflict a shocking 1.5 million people in the United States—far more than the 300,000-person figure cited by the CDC. (13) The prevalence of chronic Lyme disease is only expected to rise further in coming years, with nearly two million people expected to be affected by 2020. (14)

Some of the symptoms of chronic Lyme disease overlap with acute symptoms, including fatigue, joint pain, and sleep issues. However, chronic Lyme disease can also cause more serious dysfunctions in diverse body systems:

  • Neuropsychiatric problems, like depression, anxiety, headaches, brain fog, mood swings, emotional lability, suicidal thoughts, and cognitive dysfunction
  • Sudden-onset aggressiveness and violence, which have been observed in some cases of Lyme disease and Lyme coinfections, particularly Bartonella (15)
  • Alzheimer’s disease, shown by a well-documented relationship between Lyme and neurodegenerative diseases (16)
  • Immune dysfunction and inflammation, which is perpetuated by poor-quality sleep
  • Neuropathy, or nerve malfunction, which can be caused by nervous system inflammation in various parts of the body
  • Cardiovascular symptoms (17)
  • Issues with fetal brain development in cases where a pregnant woman has Lyme disease and it’s transmitted to her child (18)

How Does Lyme Disease Become Chronic?

While I’ll answer this nuanced question in more detail below, the short answer is that chronic Lyme develops if the disease is missed in its early stages and as a result of the complex characteristics of Borrelia burgdorferi, which allow it to evade detection by the immune system and persist in the body.

Three Mechanisms of Action of Borrelia burgdorferi

How is Lyme disease capable of causing such a diverse array of symptoms? Borrelia burgdorferi induces physiological dysfunction through several mechanisms:

1. Borrelia Causes Inflammation

Borrelia burgdorferi incites a profound systemic inflammatory response, releasing pro-inflammatory cytokines that adversely affect tissues ranging from the heart to the brain. The neuroinflammatory effects of B. burgdorferi cause peripheral neuropathy and brain inflammation, resulting in depression, anxiety, brain fog, and other neuropsychiatric symptoms. (19, 20)

2. Borrelia Downregulates Immunity

Borrelia burgdorferi downregulates host immune function, allowing it to persist in the body undetected. (21) This subsequent immune suppression makes the host more susceptible to opportunistic infections, further harming the body.

3. Borrelia May Provoke Autoimmunity

Chronic Lyme disease may also provoke autoimmunity through cross-reactivity between B. burgdorferi antibodies and self-proteins. This mechanism helps to explain why Lyme disease has been linked to multiple sclerosis, rheumatoid arthritis, and Alzheimer’s disease. (22)

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Lyme Disease Is Becoming More Prevalent and Widespread

In my previous article, 5 Myths and Truths about Chronic Lyme Disease, I debunked several common myths about Lyme disease—including the misconception that it’s a rare affliction limited to one region of the United States.

The perpetuation of these myths continues to hamper the timely diagnosis and effective treatment of the disease, causing countless people to suffer.

According to the CDC, there are more than 300,000 new cases of Lyme disease in the United States every year. (23) However, those numbers are likely skewed. Underreporting and inaccurate tests likely contribute to this—as well as the fact that many people with suspect Lyme disease don’t undergo testing before they begin treatment. As of 2018, the incidence of Lyme disease was estimated to be far greater than the 300,000-person figure reported by the CDC, instead reaching nearly 1 million people in the United States alone. By 2050, this number may rise to 55.7 million people. (24)

Many times, when patients living outside the East Coast voice their concerns about Lyme disease to their doctors, they are immediately shut down because most physicians hold the mistaken belief that Lyme can only be contracted on the East Coast. While Lyme disease was discovered on the East Coast, it is certainly not limited to that region. In fact, it has been diagnosed in all 50 states, and the ticks that carry it have been found in 43 of 50 states.  

There are several reasons why Lyme disease is expanding in geographic distribution:

  • Humans are increasingly developing natural areas, putting them in closer contact with ticks
  • Ticks can be carried across state lines by migratory birds, deer, and traveling people and pets (25)
  • Longer warm seasons due to climate change are extending the lifespan of ticks, giving them more time to infect animals and humans (26, 27)

Just as Lyme disease isn’t limited to one region, it’s not confined to rural or forested areas. Borrelia-carrying ticks are found in similar distributions in urban and suburban areas alike. (28, 29)

Other Tick-Borne Diseases and Coinfections

While Borrelia burgdorferi has long been the focus of Lyme disease research, scientists are learning that a single tick bite can transmit numerous infectious organisms, complicating Lyme disease treatment.

Ticks are reservoirs for dozens of microorganisms besides B. burgdorferi, including other types of bacteria, parasites, and viruses. Some of the organisms in ticks are not pathogenic but influence the tick’s ability to harbor and transmit pathogens, making it more virulent. (30, 31) Other tick-borne organisms are pathogenic, causing distinct sets of symptoms and complicating the clinical picture:

  • Babesiosis: Infection with Babesia microti causes anxiety, drenching sweats both day and night, shortness of breath, and heart racing.
  • Bartonella: Infection with Bartonella species causes sore throat, swollen glands, foot pain, abdominal pain, and pain in large joints such as shoulders and knees. It is also linked to neuropsychiatric disorders such as anxiety, panic disorder, rage, and sudden-onset schizophrenia. (32, 33) Bartonella is common in cats and other domestic animals and veterinarians have an increased risk of infection. (34, 35)
  • Ehrlichiosis: Ehrlichiosis causes flu-like symptoms, including a dry cough, fatigue, muscle pain, and low white blood cells. It also lowers platelets and elevates liver enzymes. The incidence of Ehrlichia infection is increasing in the United States, with most cases occurring among immunocompetent (not immunocompromised) patients. (36)
  • Rickettsia: Rickettsial infection is frequently mistaken for the flu because it produces symptoms such as fever, nausea, and vomiting. In 50 to 85 percent of people, it causes a red-spotted rash on the palms of the hands. Like Ehrlichia, it also reduces white blood cells and platelets while elevating AST and ALT. Rickettsia is believed to play a significant but underappreciated role in Lyme pathogenesis, influencing disease persistence. (37)
  • Mycoplasma: Mycoplasma pneumoniae overstimulates B cells, causing autoimmune reactions and rheumatoid diseases, fatigue, and joint and muscle pain. The weakened immunity caused by Borrelia burgdorferi makes the body more susceptible to Mycoplasma infection. (38, 39)
  • Chlamydia infections: Chlamydia infection causes arthritis, upper respiratory infections, and pneumonia and may contribute to the development of autoimmune diseases. (40)
  • Viruses: Ticks have also been found to have a high viral density, transmitting novel, harmful viral species such as the South Bay virus. (41)

Why Lyme Disease Is So Challenging to Treat

Contrary to what the CDC and IDSA would like us to believe, Lyme disease is complicated and notoriously difficult to treat. Complete eradication of B. burgdorferi spirochetes by antibiotics has not been achieved in any animal model ever tested. (42) Treatment of B. burgdorferi is difficult due to the bacterium’s ability to evade the immune system, change its morphology, and adapt to antibiotic treatments.

It Impairs the Immune System

As I mentioned earlier, Borrelia impairs host immunity, including the adaptive immune response and the complement system, the part of the immune system that enhances the ability of antibodies and phagocytes (cells that engulf bacteria and other small particles) to clear harmful microbes. (43, 44) This not only opens up the body to opportunistic infection, but also allows Borrelia to persist in the body.

It Transforms to Evade the Immune System

Borrelia also changes its own morphology to evade the immune system; it transforms from its characteristic spiral shape into a spherical cystic structure devoid of cell-surface recognition proteins. (45) It also teams up with other microorganisms, including the coinfectious agents mentioned earlier, to form a biofilm. (46, 47) Biofilm is a consortium of microorganisms embedded in a slimy extracellular matrix; when bacteria are incorporated into biofilm, they become resistant to antibiotic treatment. In the case of Lyme disease, Borrelia biofilm makes treatment even more difficult.

It Rapidly Adapts to Antibiotics

Borrelia burgdorferi rapidly alters its gene expression in response to doxycycline, one of the most commonly prescribed drugs for Lyme disease, creating an antibiotic-resistant phenotype. Doxycycline treatment of Borrelia-infected mice causes Borrelia to upregulate genes that facilitate bacterial dormancy and downregulate genes that code for cell-surface proteins; these changes cause the immune system to halt its “search” for the bacteria, allowing Borrelia to establish persistent infection. (48) B. burgdorferi has also demonstrated resistance to amoxicillin and ceftriaxone, with treatment inducing drug-tolerant “persister” cells. (49)

At Johns Hopkins University, a recent study found a three-antibiotic cocktail useful for clearing persistent Borrelia; however, it remains to be seen whether Borrelia will also adapt to combination antibiotic therapies. (50)

Lyme Transmission between People

The topic of Lyme disease transmission from one person to another is contentious. While the CDC and IDSA recognize that Lyme disease can be transmitted from a woman to her unborn child through the placenta, they maintain that “no negative effects on the fetus have been observed when the mother receives appropriate antibiotic treatment.” (51)

Conversely, the mainstream medical community vehemently argues against the idea that Lyme can be transmitted between people through other routes, such as sexual contact. However, several lines of evidence suggest that this belief is mistaken. B. burgdorferi can be cultured in the vaginal fluid and seminal secretions of infected individuals, suggesting the possibility of sexual transmission as a mode of infection. While these findings remain speculative, they certainly warrant further study. (52, 53) If Lyme disease is found to be sexually transmitted, this would have significant implications for the treatment.

How to Test for Lyme Disease

For decades, the CDC and IDSA have relied on a two-tier blood testing strategy for diagnosing Lyme disease. The first tier is an ELISA (enzyme-linked immunosorbent assay) blood test, which measures levels of antibodies against Borrelia burgdorferi. The second tier, a western blot, also tests for antibodies to B. burgdorferi but goes a step further by reporting reactivity to 10 different proteins found in the bacterium. However, the two-tier testing strategy poses multiple problems:

  1. The two-tier approach has a low sensitivity (the ability to correctly identify those with the disease) of 30 to 40 percent in the early stages of Lyme disease; for those of you not familiar with biostatistics, this is pretty abysmal. At all stages of Lyme disease, including the often devastating later stages, the sensitivity of the two-tier algorithm increases to only 57.6 percent. (54, 55)
  2. The western blot does not pick up on many naturally occurring strains of Borrelia that cause disease. Because the western blot uses antigens from cultured strains of Borrelia, not clinical specimens, it does not pick up on many disease-causing strains of Borrelia that naturally occur in our environment.
  3. The western blot is prone to methodological issues and subjectivity in interpretation. Slight variations in the western blot methodology and the highly subjective nature of western blot interpretation can lead to false negatives.

Clearly, our current “gold standard” blood testing strategy for Lyme disease is insufficient. But what tests should be used instead? In my work, I’ve found a combination approach to be the most useful for diagnosing Lyme disease.

Serologic Testing

As a first step, we recommend serologic tests for Lyme disease. Serologic tests include the ELISA, the western blot, and the immunoblot, a new test that is more sensitive than the western blot and is designed to take its place. (56) Serologic Lyme tests can be done through Stony Brook University, Quest, LabCorp, or IGeneX.

Molecular Testing

If serologic tests come back negative, but Lyme disease is still strongly suspected, next-generation molecular Lyme tests can be used to supplement the serologic results. The EliSpot from ArminLabs assesses the T-cell immune response to Borrelia burgdorferi, thus reflecting current Lyme disease activity. The test becomes negative when B. burgdorferi is no longer active, making it useful for monitoring treatment.

Global Lyme Diagnostics offers the GLD test, which tests for the presence of antibodies to B. burgdorferi outer surface proteins, thereby expanding the number of species and strains that can be detected. The diversity of targets identified by the test significantly reduces false negatives.

Ceres Nanoscience, another cutting-edge company offering diagnostic solutions for Lyme, offers the Nanotrap Lyme Antigen Test. This test concentrates Lyme antigens in urine and then detects the antigens using an ELISA and western blot.

Importantly, we do not recommend testing for Lyme with PCR technology. While PCR-based tests, such as DNA Connexions, once seemed promising, they frequently produce false positives and demonstrate low sensitivity. (57)

Metabolomics: The Future of Lyme Disease Testing?

Last but not least, the field of metabolomics holds promise for future testing of Lyme disease. Metabolomics involved testing for the biosignature of Lyme disease, characterized by specific proteins and other metabolites either produced directly by the bacterium or by the body in response to the bacterium. (58)

Lyme Disease Is “the Great Imitator”

The diagnosis of Lyme disease is further complicated by the fact that it mimics many other conditions. In many cases, this leads to misdiagnosis. Before Lyme disease was first recognized in Lyme, Connecticut, it was mistaken for juvenile arthritis. (59) Lyme has also been misdiagnosed as multiple sclerosis, neuropsychiatric disorders, and Alzheimer’s disease. In some cases, untreated chronic Lyme disease may lead to these conditions, so the “misdiagnosis” may be partially correct even though it does not consider the underlying cause of the disease process. (60, 61, 62)

How You Can Prevent Lyme Disease

The simplest way to prevent Lyme disease is to avoid tick bites. Here’s a quick review of how to prevent tick bites and what steps to take if you are bitten. For more, check out my article “What to Do about a Tick Bite.”

Be Conscious in the Outdoors

Whenever you embark on a hike, walk, picnic, or any other activity outdoors, stick to well-groomed paths and avoid tall grasses. Tall grasses are one of the favorite habitats of ticks; when searching for a host to feed on, animal or human, ticks climb to the outer tips of the grass and wave their legs around, waiting to hitch a ride on an unsuspecting passerby. (63) Avoid walking through leaf litter or sitting on logs because ticks also like to hang out in these locations.

Use Insect Repellant

Insect repellant is critical for warding off ticks and other disease-carrying biting insects, such as mosquitos. You have several options for an effective repellant:

  • Lemon eucalyptus oil, which is natural, non-toxic, and as effective as DEET for deterring ticks and mosquitos (64, 65)
  • Permethrin, a synthetic insect repellant derived from chrysanthemums
  • DEET, for extreme tick exposure situations

In general, I recommend starting with a safe option like lemon eucalyptus oil. Permethrin and DEET should be used with caution.

Perform Regular “Tick Checks”

When you return home from the outdoors in tick-endemic areas, change your clothes and put the used clothes in the dryer for 20 minutes—the heat will kill any ticks that hitched a ride. Next, perform thorough tick checks on your children, partner, and pets, and then have somebody check you. Be sure to examine your entire body, and check your children before bed and nightly if they have been playing outside.

Nymph ticks, the primary tick vector for Lyme disease, are the size of poppy seeds and thus quite hard to detect. You may need to use a magnifying glass. If you have an iPhone or Android, you can use the built-in magnifier tools, or you may want to keep a small magnifying glass at home for this purpose.

Safely Remove an Attached Tick

If you’ve been bitten by a tick, it is crucial that you promptly remove the tick using the proper removal technique. I recommend using a pair of TickEase tweezers, which have a fine tip specially designed for tick removal. Keep a pair in your purse, hiking backpack, car, and at home.

Here’s how to remove a tick safely:

  1. Grasp the tick with the tweezers, getting as close to the skin as possible
  2. Slowly and steadily lift up on the tick, perpendicular to where it’s attached
  3. Maintain pressure and wait for the tick to release

Don’t squeeze the body of the tick, twist it, burn it, or try any other home remedies. This can increase the risk of infection, as the tick might regurgitate its stomach contents into the bite area.

For more information on tick removal, see the Bay Area Lyme Foundation’s helpful webpage on tick removal.

Get the Tick Tested for Pathogens

Once you’ve removed the tick, place it in a plastic bag with a moist paper towel and save it for identification and pathogen testing. You can try identifying the tick yourself using a resource like TickEncounter. Understanding what type of tick bit you can help your doctor decide whether or not to begin treatment for Lyme disease while waiting on the results of pathogen testing.

You have a few options to have the tick tested for pathogens, like:

  • TickReport, which offers comprehensive pathogen testing and a quick turnaround time of 72 hours, and
  • The Bay Area Lyme Foundation, which offers free—albeit slower—testing services

Pathogen testing can determine whether or not the tick that bit you carried Borrelia burgdorferi. Knowing that sooner rather than later can give your doctor the chance to begin treatment immediately, which can could help prevent chronic Lyme disease complications.

In some cases, your doctor may choose to begin treatment before receiving the results of pathogen testing (or in cases where testing wasn’t possible). Several factors go into a choice like this, including where you live, the type of tick that bit you, and how long it was attached before removal. I recommend consulting closely with your doctor to determine the right course of action for you.

Why a Functional Medicine Approach Is Best for Chronic Lyme Disease

The conventional medical approach to treating Lyme disease is very limited and, while antibiotics have their place in Lyme treatment, they do not correct the immune dysfunction, inflammation, and other metabolic derangements caused by the disease. Functional Medicine offers an entirely different approach—one that considers patient health from a whole-body perspective and works to correct the systematic dysfunctions characteristic of chronic Lyme disease. While every Functional Medicine protocol for Lyme will be somewhat different, you can expect to see the following:

  • An anti-inflammatory diet and targeted nutritional support: Proper nutrition helps support healthy immune function and decrease Lyme-induced inflammation, providing a foundation for recovery.
  • Antimicrobials: Both pharmaceutical and botanical antimicrobials have a place in the Functional Medicine approach to Lyme disease.
  • Immune system and anti-inflammatory support: Both of these are crucial for Lyme recovery.
  • Gut healing: The various coinfections transmitted in a tick bite can disrupt the gut microbiota, setting the stage for gut dysfunction and systemic inflammation. Like diet, supporting gut health should be a foundational part of any Lyme treatment protocol.
  • Mold exposure: Many patients with chronic Lyme disease also have a history of mold exposure that further compromises their immunity. Mold exposure is just one of several environmentally acquired illnesses that Functional Medicine can address in people with Lyme disease.
If you’ve been bitten by a tick and suspect you may have Lyme disease, it’s crucial that you get help as soon as possible. The California Center for Functional Medicine offers a membership-based, health transformation program that gives you the tools, the team, and the support you need to reclaim your health. Find out how we can help.

For more resources on Lyme disease:

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