Follow-Up Testing in Lyme Disease: Why It Matters
An initial Lyme disease test may be negative
Symptoms can change or worsen after the first evaluation
Follow-up may include clinical reassessment, repeat testing, or additional studies
Why does follow-up testing matter in Lyme disease? A published case involving a 75-year-old New York resident demonstrates how an initially negative Lyme disease test may not resolve the diagnosis when symptoms continue to evolve.
The patient developed fever, confusion, muscle pain, weakness, and an unstable gait. Repeat blood testing and cerebrospinal fluid findings later supported a diagnosis of Lyme neuroborreliosis.
An Unstable Gait Without a Known Tick Bite
Lamichhane and colleagues described a 75-year-old man living in suburban New York who presented with an unstable gait, fever, malaise, muscle pain, and confusion.
He had not recently traveled and reported only taking walks in a local park. He did not recall a tick bite.
At his initial examination, the patient denied several symptoms that might have suggested a neurologic or systemic illness, including:
- Headache
- Dizziness
- Rash
- Focal weakness
- Loss of sensation
- Chest or back pain
The absence of a known tick bite or characteristic rash did not exclude Lyme disease.
Symptoms Worsened After the Initial Evaluation
The man was discharged but returned four days later with a more severe illness. His symptoms now included:
- Fever
- Rigors and chills
- Heavy sweating
- Diffuse muscle pain
- Generalized weakness
- Malaise
- Confusion
- Decreased appetite
His initial Lyme disease enzyme immunoassay had been negative.
Imaging identified splenomegaly, a splenic infarct, and a small aneurysmal dilation of the thoracic aorta. These findings required clinicians to consider other serious infectious and vascular conditions.
The patient received ceftriaxone, ampicillin, and vancomycin, but his condition continued to deteriorate during the following 24 hours.
Repeat Lyme Disease Tests Produced Different Results
Because the patient’s condition had changed, clinicians continued the evaluation and repeated the tick-borne disease testing.
The subsequent laboratory findings included:
- Positive Lyme IgM and IgG enzyme immunoassays
- Positive Lyme IgM immunoblot
- Lyme antibodies detected in cerebrospinal fluid
- Positive Babesia microti IgM and IgG antibodies
The evolving clinical presentation, repeat blood tests, and spinal fluid findings supported the diagnosis of Lyme neuroborreliosis.
The spinal tap was not the only positive test. The repeat blood tests were also positive. The case instead demonstrates why clinicians may need to reconsider an initial negative result when a compatible illness persists or worsens.
Improvement After Doxycycline
The patient was diagnosed with Lyme neuroborreliosis and prescribed doxycycline for 21 days.
According to the authors, his mental status returned to baseline and his gait normalized within 48 hours after doxycycline was started.
His improvement was consistent with the clinical diagnosis, although a response to treatment does not independently prove that an infection caused every symptom or abnormal finding.
For a more detailed discussion of this patient’s presentation, see:
Negative Lyme Disease Test: 75-Year-Old Man Diagnosed With Neuroborreliosis
Follow-Up Means More Than Repeating the Same Test
Follow-up evaluation does not necessarily mean repeatedly ordering Lyme disease antibody tests.
Depending on the patient’s symptoms and clinical course, follow-up may include:
- Reviewing how the symptoms have changed
- Repeating the physical and neurologic examination
- Reconsidering the timing of the original Lyme disease test
- Evaluating alternative diagnoses
- Assessing for possible tick-borne coinfections
- Ordering additional studies when neurologic, cardiac, or other serious complications are suspected
Repeat serologic testing may be informative when the initial test was performed before detectable antibodies had developed. However, positive antibodies can remain detectable after an infection has resolved. Therefore, repeat test results must be interpreted within the full clinical context.
How Should the Babesia Antibody Results Be Interpreted?
The patient also had positive Babesia microti IgM and IgG antibody results.
These results indicated exposure to Babesia microti, but antibodies alone do not necessarily establish active babesiosis. A positive blood smear or PCR test can provide stronger evidence of active parasitemia.
Nevertheless, babesiosis was reasonable to consider because the patient lived in an endemic region and had high fever, sweats, splenomegaly, and a splenic infarct.
Lyme disease and babesiosis are transmitted by the same type of tick in the northeastern United States, making coinfection possible.
Why Clinical Follow-Up Remains Important After Treatment
Follow-up also matters after treatment has been completed.
Some patients recover quickly, while others report persistent fatigue, pain, cognitive difficulties, or other symptoms. These symptoms require careful evaluation because they may reflect several possibilities, including:
- Slow recovery following infection
- A complication of Lyme disease
- An unrecognized coinfection
- Treatment-related adverse effects
- Another medical condition
A study by Dersch and colleagues found that fatigue and reduced quality of life were reported by some previously treated patients with definite Lyme neuroborreliosis. However, the study did not establish that ongoing infection caused every persistent symptom.
Follow-up should therefore focus on the individual patient rather than relying on one laboratory result.
Clinical Takeaway
An initial negative Lyme disease test should not automatically end the evaluation when a patient’s symptoms continue to evolve.
This case highlights several practical lessons:
- Patients may not remember a tick bite.
- A characteristic rash may be absent.
- Antibody tests may be negative early in an infection.
- Repeat testing can sometimes produce different results.
- Neurologic symptoms may require additional evaluation.
- Positive antibody tests must be interpreted within the clinical context.
- Follow-up should include reassessment of symptoms, not testing alone.
This single case cannot determine how frequently an initial Lyme disease test misses neuroborreliosis. It does demonstrate why continued clinical observation and reassessment can be important when a patient’s condition worsens.
Frequently Asked Questions
Can an initial Lyme disease test be negative?
Yes. Antibodies may not yet be detectable during the early stage of an infection. Test timing, disease stage, previous treatment, and the patient’s clinical presentation can all affect interpretation.
Should every negative Lyme disease test be repeated?
No. Repeat testing is not automatically appropriate for every patient. The decision depends on the timing of the initial test, symptoms, exposure risk, physical findings, and whether the illness continues to evolve.
Does follow-up testing prove that Lyme disease is active?
Not necessarily. Lyme antibodies can remain positive after treatment and do not function as a test of cure. Laboratory findings must be interpreted alongside the patient’s symptoms and clinical history.
Does a positive spinal fluid antibody test prove neuroborreliosis?
Not by itself. Cerebrospinal fluid findings should be interpreted with paired blood testing, evidence of antibody production within the central nervous system, spinal fluid inflammation, and compatible neurologic findings.
Do positive Babesia antibodies prove active babesiosis?
No. Antibodies may reflect recent or previous exposure. A blood smear or PCR test may provide stronger evidence of active infection when babesiosis is suspected.
References
- Lamichhane J, Haider R, Bekkerman M, et al. A case of undetected neuroborreliosis in a 75-year-old Chinese male. Case Rep Infect Dis. 2018;2018:6764894. doi:10.1155/2018/6764894.
- Dersch R, Sarnes AA, Maul M, et al. Quality of life, fatigue, depression and cognitive impairment in Lyme neuroborreliosis. J Neurol. 2015;262(11):2572–2577. doi:10.1007/s00415-015-7891-4.
This article discusses a published case report and is provided for educational purposes. It is not a substitute for individual medical evaluation or treatment.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
