Lyme disease sits in an unusual place in modern medicine: well known by name, poorly understood in practice, and the source of genuine, ongoing disagreement even among specialists. For patients caught in the middle, that disagreement isn't academic, it often means years of vague symptoms, dismissed complaints, and a diagnosis that arrives only after a long, frustrating search.
Lyme disease entered public awareness roughly forty years ago, after a cluster of children in Lyme, Connecticut began developing symptoms resembling rheumatoid arthritis. Since then, reported cases have climbed nearly fivefold over the past 25 years, driven partly by a changing climate that has expanded the range of the ticks that carry it well beyond its original Northeast footprint. It's now considered a genuine public health concern across most of the country, transmitted through a single tick bite that can happen during an entirely ordinary walk through grass or brush.
The bacterium responsible, Borrelia burgdorferi, is a corkscrew-shaped spirochete covered in a protective biofilm that helps it evade immune detection. It migrates from the bloodstream into tissue, which makes it difficult to culture directly since it isn't present in sufficient concentration in body fluids to test for reliably. Left untreated, it can spread into the joints, spinal cord, brain, and even the heart, where it can cause a potentially fatal condition called Lyme carditis.
Complicating matters further, standard Lyme tests look for antibodies rather than the bacterium itself. This indirect approach can miss early infection entirely and can't reliably distinguish an active infection from one that's already been cleared, or determine whether a positive result reflects a new infection at all. Antibodies related to autoimmune conditions and certain viral infections can also resemble the ones the body produces in response to Lyme, adding another layer of diagnostic uncertainty. More accurate testing exists for Lyme and its common co-infections, but it's often not covered by insurance and can cost patients thousands of dollars out of pocket.
For a meaningful subset of patients, symptoms like brain fog, joint pain, and fatigue persist even after completing the standard antibiotic protocol. This phenomenon, now recognized by the CDC under the name post-treatment Lyme disease syndrome (PTLDS), has been documented in studies showing persistent symptoms in as many as 20% of treated patients. Even researchers within the CDC have acknowledged publicly that patients have gone far too long without clear answers about why this happens or how best to treat it.
Allen Steere, the rheumatologist credited with first identifying Lyme disease, has suggested multiple factors may be at play, including lingering joint inflammation that persists after the bacteria itself is gone, other undiagnosed illnesses contributing to symptoms, and in some patients, a genetic predisposition toward an exaggerated inflammatory response. That genetic research has since informed more effective treatments for Lyme-related arthritis using anti-rheumatic medications.
One of the more compelling emerging explanations for PTLDS involves what researchers call "persister bacteria," a phenomenon also documented in staph infections. Research from Johns Hopkins found that Borrelia burgdorferi can survive in some mammals even after a full course of antibiotic treatment, in dormant form, able to evade drugs like doxycycline that work by inhibiting bacterial replication rather than killing the bacteria outright. Because dormant bacteria aren't actively dividing, standard treatment may simply not reach them, leaving the immune system to finish the job on its own, something that doesn't always happen completely.
When researchers applied a multi-drug protocol used for persistent staph infections to this problem, including an antibiotic specifically known to target dormant bacterial cells, they were able to clear the lingering infection in animal studies. This gives researchers both a plausible biological explanation and a potential treatment direction for patients whose symptoms don't resolve with standard care, though human studies on this specific approach are still ongoing.
Physicians specializing in infectious disease have been candid that even the most knowledgeable experts remain genuinely uncertain about important aspects of Lyme disease and PTLDS. That uncertainty is exactly why a personalized, concierge-style approach matters so much for patients dealing with rare or poorly understood chronic conditions: immune responses to Lyme vary enormously from patient to patient, lab testing often can't confirm or rule out active disease definitively at any single point in time, and effective treatment frequently requires ongoing follow-up rather than a single diagnosis-and-done encounter.
At Liondale Medical, Lionel Bissoon, DO, brings this kind of individualized, diagnostic-first approach to patients dealing with Lyme disease and related chronic symptoms. Rather than applying a single standard protocol regardless of how a patient is actually responding, treatment is built around ongoing testing, symptom tracking, and adjustment as new information emerges, an approach that matters most precisely in cases like this, where the underlying science is still evolving.
Part of what makes Lyme disease so disorienting for patients is that it isn't just a diagnostic puzzle, it's a genuine, long-running disagreement within medicine itself about how the disease should be treated once initial antibiotics don't fully resolve symptoms. One camp, generally aligned with the Infectious Diseases Society of America (IDSA), holds that a standard, time-limited course of antibiotics is sufficient to clear the infection in the vast majority of cases, and that lingering symptoms afterward are more likely explained by another cause, residual inflammation, an unrelated condition, or a separate immune response, rather than ongoing active infection. A second camp, often associated with the International Lyme and Associated Diseases Society (ILADS), takes the position that Borrelia burgdorferi can persist in some patients despite standard treatment, and that longer or repeated courses of antibiotics may be warranted for patients whose symptoms don't resolve.
This isn't a fringe disagreement, it's played out in clinical guidelines, insurance coverage decisions, and, for patients, in the difference between a doctor who says "you're cured, the symptoms must be something else" and one willing to keep investigating. Neither camp has been definitively proven right for every case, which is exactly why individualized, ongoing evaluation matters more here than in conditions where the standard of care is settled and uncontroversial.
Understanding the shape of a typical Lyme disease experience helps explain why so many patients describe feeling dismissed before finally getting answers. It often starts with a vague cluster of symptoms, fatigue, joint aches, brain fog, that don't point clearly to Lyme disease on their own and get initially worked up for more common explanations: thyroid dysfunction, an autoimmune condition, depression, or simple overwork. Standard bloodwork for these other conditions often comes back inconclusive or only partially explanatory, and a patient may be told their labs are "basically normal" even as symptoms persist or worsen.
If Lyme testing is eventually ordered, the two-tiered antibody test used in most clinical settings can return an ambiguous result, positive on one component but not the other, which doesn't neatly confirm or rule out the diagnosis. At this point, treatment decisions become genuinely judgment-based, weighing symptom history, potential exposure, and test results together rather than relying on a single definitive lab value the way many other infections allow. Patients who respond well to standard antibiotic treatment often recover within weeks to a few months. Those who don't are the ones who end up navigating the disagreement between treatment philosophies described above, sometimes for years, before finding a provider willing to continue investigating rather than closing the case.
Part of why so much about Lyme disease and PTLDS remains unresolved comes down to research funding, which has historically been modest relative to the disease's actual public health burden. Government research dollars per newly diagnosed Lyme case are a small fraction of the funding allocated to some other infectious diseases with comparable or even lower case counts, leaving much of the research into persistent symptoms and treatment-resistant cases to smaller academic labs and private funding sources rather than large, well-resourced clinical trial programs. This funding gap is a meaningful part of the honest answer to "why don't we know more yet," and it's part of why the science here continues to evolve rather than having settled into firm consensus.
For patients managing persistent symptoms even after antibiotic treatment, additional supportive therapies can play a role alongside standard medical care. Medical ozone therapy is one option some patients explore for its anti-inflammatory and immune-supportive effects, discussed in more depth in our overview of ozone therapy. Patients dealing with the fatigue and nutrient depletion that often accompanies a prolonged illness may also benefit from IV therapy to address deficiencies identified through lab testing.
None of the above should overshadow the most effective tool available: avoiding the bite in the first place. Ticks are most active in warmer months but can be encountered nearly year-round in milder climates, and they're often found in tall grass, leaf litter, and brush rather than deep forest alone, meaning a suburban backyard or a city park edge can carry real risk. Checking your body carefully after time outdoors, wearing long sleeves and pants treated with permethrin in high-risk areas, and removing an attached tick promptly and correctly all meaningfully reduce transmission risk, since the bacterium typically needs 24 to 48 hours of attachment to transmit effectively. If you find an attached tick, saving it (or at least photographing it) and noting the date can be genuinely useful information for a provider later, even if you feel fine at the time.
If you're pursuing a Lyme disease evaluation, coming prepared helps your provider build an accurate picture faster. Useful information includes a timeline of when symptoms started and how they've evolved, any prior lab results even if they were inconclusive or negative, a note on any known tick bites or time spent in tick-prone areas (even if it was months or years ago, since exposure isn't always noticed at the time), and a list of other diagnoses that have been considered or ruled out along the way. Patients often assume a prior negative test rules out Lyme disease entirely, but given the limitations of standard antibody testing described earlier, a negative result doesn't always close the door, particularly if it was run early in a possible infection or if co-infections weren't tested for separately.
Standard tests look for antibodies rather than the bacterium itself, which can miss early infection and can't reliably distinguish an active infection from a past, cleared one. More accurate testing exists but is often not covered by insurance.
PTLDS refers to persistent symptoms like brain fog, joint pain, and fatigue that continue even after a patient completes standard antibiotic treatment for Lyme disease. It's recognized by the CDC and affects a meaningful subset of treated patients.
Persister bacteria are dormant forms of Borrelia burgdorferi that can survive standard antibiotic treatment because they aren't actively dividing when the antibiotic is working. Research suggests multi-drug protocols may help address this in some patients, though human studies are still developing.
Because Lyme and PTLDS involve highly individual immune responses and diagnostic uncertainty, a personalized approach with ongoing testing and adjustment tends to serve patients better than a single standardized protocol applied uniformly.
Alongside standard medical care, some patients explore medical ozone therapy for its anti-inflammatory effects or IV therapy to address nutrient deficiencies that often accompany prolonged illness.
If you're dealing with persistent, unexplained symptoms and suspect Lyme disease may be part of the picture, schedule a consultation with Dr. Bissoon at Liondale Medical.
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