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When Lyme Disease Symptoms Persist: What Do We Actually Know?

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"Chronic Lyme doesn't even exist."

It's a statement frequently encountered in medical discussions, often delivered as though it settles the matter. But what exactly is being rejected? An untreated infection lasting years? A new infection following another tick bite? Persistent symptoms after antibiotics? Or the disputed hypothesis that viable bacteria routinely survive adequate treatment and cause ongoing illness?

These are different medical questions. The term "chronic Lyme disease" has been used to describe all of them, which is precisely why many medical authorities discourage it. But rejecting an imprecise term does not resolve the conditions and uncertainties that term may be used to describe. Before dismissing the patient's language, we need to establish what the patient is actually reporting.


What can persist, and for how long?

Lyme disease is caused by bacteria belonging to the Borrelia burgdorferi sensu lato group. Untreated infection can progress beyond its early manifestations and affect the nervous system, joints, skin and occasionally the heart. Some late manifestations can develop or persist years after the original infection.

One example is acrodermatitis chronica atrophicans (ACA), a late skin manifestation associated particularly with Borrelia afzelii in Europe. ACA can develop gradually over many years, and viable Borrelia organisms have been recovered from affected skin. This demonstrates that prolonged active infection can occur in humans when Lyme disease remains untreated. It does not establish that every person with longstanding symptoms has an active infection, nor does it establish bacterial survival following adequate treatment.

Reinfection is another established possibility. A previous episode of Lyme disease does not provide reliable lifelong immunity. In a 2012 study published in the New England Journal of Medicine, researchers examined patients with recurrent Lyme disease and found that successive episodes involved genetically distinct bacterial strains. Their findings supported reinfection rather than relapse. A person experiencing Lyme disease for a second time may therefore have acquired a new infection rather than experienced the return of the original one.

Then there is the more disputed possibility of bacteria surviving adequate antibiotic treatment and contributing to prolonged illness. Laboratory and animal research has identified antibiotic-tolerant Borrelia under certain conditions, but this does not establish that viable persistent infection is the general cause of symptoms following recommended treatment in humans. That distinction matters. Biological plausibility, experimental observations and demonstrated human disease are not equivalent levels of evidence.


When antibiotics don't resolve the problem

Recommended antibiotics are effective for most patients with Lyme disease, but treatment outcomes are not always straightforward. Some patients with Lyme arthritis have an inadequate response to an initial oral antibiotic course. Established guidelines describe circumstances in which further assessment and additional treatment may be appropriate. They also recognise that persistent joint inflammation can continue through immune-mediated mechanisms after the infection has been treated.

There is no routinely recommended, validated microbiological test of cure for Lyme disease. Standard antibody tests measure the immune response and can remain positive for years after successful treatment. A positive antibody result therefore does not demonstrate continuing infection, while negative results must be interpreted in relation to the timing of infection, the clinical presentation and the tests used. Early infection, for example, may precede a detectable antibody response.

None of this means that clinicians should presume antibiotic failure whenever symptoms persist. It means that treatment history and clinical recovery need to be assessed separately. Was the original infection adequately documented? Was the treatment appropriate for the manifestation? Did the patient recover and later become ill again? Are there objective findings suggesting reinfection, complications or another disease? These questions cannot be answered merely by saying that antibiotics were prescribed.

At the same time, a reported improvement after antibiotics is not, by itself, proof of Lyme disease. Symptoms can fluctuate, treatments may have effects unrelated to the suspected pathogen, and other conditions may be present. Treatment response can be useful clinical information without functioning as a definitive diagnostic test.


PTLDS: persistent illness without a settled explanation

Post-Treatment Lyme Disease Syndrome (PTLDS) refers to a recognised pattern of persistent symptoms following treatment for Lyme disease. Patients may experience fatigue, pain, cognitive difficulties and reduced functioning long after completing antibiotics. The US Centers for Disease Control and Prevention acknowledges these persistent symptoms while noting that their cause remains uncertain.

Proposed mechanisms include lasting tissue or nerve injury, immune and inflammatory changes, persistent bacterial components and other post-infectious processes. Whether viable bacteria persist and contribute to illness in some appropriately treated patients remains a research question, not an established general explanation for PTLDS. Clinical trials have not demonstrated reliable sustained benefits from prolonged antibiotic treatment for persistent nonspecific symptoms, and such treatment can cause serious harm.

PTLDS therefore occupies an important position in this discussion. It acknowledges that patients can remain genuinely ill after treatment without requiring clinicians to assume that active infection continues. But recognising PTLDS does not mean that every subsequent symptom has been explained, that other diagnoses have been excluded or that no further assessment will ever be necessary.

There is also overlap with other post-infectious illnesses. Some people with PTLDS report symptom patterns resembling those found in ME/CFS, including substantial fatigue and impaired functioning. Shared symptoms do not establish that the conditions have identical mechanisms, but they illustrate why prolonged illness cannot always be understood through the original infection alone.


What patients have reported on FND Nope

These questions are not confined to theoretical discussions. In ANTIBIOTICS CURED ME OF FND!, a contributor describes a history of tick exposure, an earlier expanding rash, neurological and systemic symptoms, an FND diagnosis and reported improvement following antibiotic treatment. The account also describes negative conventional Lyme testing, private investigations and concerns about possible additional tick-borne infections.

What makes this account particularly concerning is the combination of a reported untreated erythema migrans rash, neurological symptoms, optic nerve damage and improvement following antibiotic treatment. These details deserve serious clinical consideration, especially when the patient reports that further investigation became difficult after receiving an FND diagnosis. Whether Lyme disease, another tick-borne infection or a combination of conditions explains her illness remains a clinical question. The point is that an FND label should not bring that investigation to an end.

The comments beneath that article are particularly instructive. A sceptical contributor challenged the interpretation of Lyme testing, questioned the private diagnostic methods and argued that the reported history was more consistent with FND. Other participants challenged the strength of those conclusions, raised the possibility of different infections or repeated exposure, and discussed the overlap between PTLDS and ME/CFS.

One issue emerged repeatedly: neither a patient's confidence in an infectious explanation nor a critic's confidence in FND can substitute for evidence. A disputed private test should not be accepted uncritically, but identifying weaknesses in that test does not independently establish FND. Likewise, an antibiotic response deserves consideration without being treated as microbiological proof. The appropriate conclusion may remain uncertain.

A second account, Another case of Lyme disease attributed to FND, due to negative Lyme testing, describes Maja Bagdziun's experience, originally shared with Lyme Disease UK. She reports tick bites, erythema migrans rashes, neurological symptoms and an FND diagnosis following negative investigations. She also describes findings involving orthostatic intolerance and visual symptoms that she felt were not adequately explained.

Her account raises a different but related question: how should clinicians weigh a history of characteristic erythema migrans against subsequent negative tests and an evolving neurological presentation? Under NICE guidance, a typical erythema migrans rash can support a clinical Lyme diagnosis without laboratory confirmation. That does not establish that all later symptoms are caused by active Lyme infection, but it means the clinical history cannot simply be reduced to the result of a blood test.

In the comments beneath that article, FND Nope made a distinction worth retaining: describing how symptoms present is not the same as explaining why they occur. Recognising a functional-looking presentation does not, by itself, establish a functional cause. Equally, recognising symptoms compatible with Lyme disease does not establish that Lyme is responsible. Both conclusions require appropriate supporting evidence.


Clinical language versus patient language

There is a broader problem here, one previously raised in FND Nope's Open Letter to Zachary Grin, DPT. Patients and caregivers are not necessarily clinicians. They may describe an evolving illness using everyday language, incomplete terminology or provisional diagnoses. Their understanding may change as investigations proceed and new information emerges.

Clinical terminology is designed to distinguish between possibilities that ordinary language often groups together. That precision is valuable. A clinician is justified in explaining why persistent symptoms after Lyme treatment do not automatically establish persistent infection, just as it is important to distinguish a suspected diagnosis from a confirmed one.

But correcting terminology is not the same as disproving the underlying clinical concern. A patient saying "my Lyme never went away" might mean that symptoms continued after treatment, that they were never adequately treated, that they became ill again after another tick bite, or that they believe the original infection remains active. Those claims are not equivalent, and the clinician should establish which one is actually being made before responding.

Conversely, patients should not be encouraged to treat every uncertainty as evidence for their preferred explanation. If a patient describes persistent symptoms as "chronic Lyme," that wording does not demonstrate continuing bacterial infection. The responsibility on both sides is to distinguish observations, interpretations and confirmed findings.

The principle is straightforward: imprecise language is a reason to ask a clarifying question, not a reason to dismiss a patient's entire account. Clinical expertise should help translate the patient's description into medically testable questions. It should not turn a disagreement over terminology into unwarranted diagnostic certainty.


Where does FND enter the picture?

Consider a patient with a history of Lyme disease who continues experiencing weakness, dizziness, sensory disturbances or cognitive difficulties. Some of these symptoms may occur in recognised Lyme-related complications, PTLDS or entirely different conditions. They may also overlap with presentations described in FND literature. The existence of overlapping symptoms does not determine which diagnosis is correct.

An especially relevant example appears in the 2018 paper You've made the diagnosis of functional neurological disorder: now what?. Its photographic educational vignette depicts a patient diagnosed with functional gait disorder who returns to her neurologist and reports that her internist suspects Lyme disease. She says antibiotics may be helping and asks whether something has been missed.

Educational FND consultation cartoon showing a patient questioning her diagnosis after another clinician suspects Lyme disease.
Figure 1: An educational cartoon from the 2018 paper You've made the diagnosis of functional neurological disorder: now what? depicts a patient questioning her FND diagnosis after her internist suspects Lyme disease and antibiotics appear to offer some improvement. The illustration raises questions about how competing diagnoses are evaluated when patients are encouraged to accept an FND diagnosis.

The neurologist reminds her that the FND diagnosis is based on examination findings, offers to show her an online video and encourages her to reconsider the diagnosis. The final panel also proposes contacting her internist and arranging follow-up, an important detail that should not be omitted. Nevertheless, the illustration does not show how the possible Lyme diagnosis is evaluated. Its central educational emphasis is on helping the patient accept FND.

That emphasis deserves examination. As we've established, Lyme disease involves several distinct possibilities: untreated infection, reinfection, an inadequate treatment response, recognised post-treatment illness and alternative explanations for persistent symptoms. The patient's question cannot be answered simply by establishing that an FND-compatible examination finding was observed. The suspected infectious condition requires assessment on its own merits.

The comic is not evidence that this fictional patient had Lyme disease or PTLDS, nor does it demonstrate that clinicians routinely misdiagnose either condition as FND. What it illustrates is a potential tension in clinical communication: when a patient raises an alternative explanation, is the priority to investigate the discrepancy, clarify what is being proposed or secure acceptance of the existing diagnosis?

Positive examination findings can support an FND diagnosis, but they do not independently prove that another disease is absent. Likewise, a history of infection does not invalidate positive FND findings. Coexisting conditions are possible, and clinical reasoning must account for that possibility without automatically assuming either coexistence or misdiagnosis.

There is currently insufficient evidence to establish how frequently PTLDS is overlooked in patients subsequently diagnosed with FND, how often these diagnoses coexist or whether systematic misclassification is occurring. Those are questions for further research, not conclusions that can responsibly be drawn from a handful of patient accounts or an educational illustration.


What remains unanswered?

The available evidence supports several conclusions at once. Untreated Lyme infection can persist for years. Reinfection is documented. Some patients need reassessment or further treatment following an inadequate initial response. PTLDS is recognised, although its mechanisms remain incompletely understood. Persistent active infection following adequate treatment has not been established as the general cause of PTLDS, and prolonged antibiotics have not shown reliable sustained benefit for these symptoms.

None of those findings requires us to accept every claim made under the label "chronic Lyme disease." But neither do they justify dismissing every patient who uses that terminology. The appropriate response depends on what is being claimed, what has been documented and what remains uncertain.

The same evidential standard should apply when FND is considered. A clinician should not diagnose continuing Lyme infection merely because symptoms persist, but neither should a functional explanation become the default simply because the infectious explanation has not been established. An uncertain diagnosis does not automatically validate its alternative.

Persistent symptoms do not prove persistent infection. Negative or inconclusive investigations do not automatically establish FND. And correcting a patient's terminology is not the same as resolving their medical problem.

The important question is not whether a disputed label should be accepted or rejected in every circumstance. It is whether clinicians and patients are distinguishing what is known, what is suspected and what still requires investigation. That distinction matters far more than winning an argument over the word "chronic."


References and related reading