Treatment for Lyme disease cannot be considered complete on the final day of the course of antibiotics. Proper follow-up is a fundamental part of patient care, particularly because clinical improvement, the immunological response and the timeline of laboratory results often differ from one another. In everyday practice, it is often difficult to determine whether a persistent symptom is attributable to active infection, slow recovery or possibly another comorbidity. The follow-up of Lyme borreliosis cannot therefore be reduced to serological monitoring: it requires a complex clinical assessment, differential diagnostic reasoning and an individualised monitoring strategy.
The most important indicator of therapeutic success remains improvement in the clinical condition. In cases of early infection – for example, in the presence of erythema migrans – the skin symptom usually fades within a few weeks and then disappears. However, the rate of regression may vary from person to person, and slow improvement alone should not be regarded as a failure of treatment. Similarly, the patient may still report fatigue, difficulty concentrating or mild musculoskeletal complaints even weeks after antibiotic treatment. When assessing these, it is crucial to determine whether the symptoms show a trend towards improvement or whether progression is observed.
The timing of follow-up examinations is determined by the clinical presentation. In early-stage Lyme disease, a follow-up examination 4–6 weeks after the end of treatment is generally sufficient. However, in cases of disseminated infection, neurological involvement, carditis or Lyme arthritis, follow-up for several months, and in some cases for over a year, may be necessary. It is important to emphasise that regular follow-up is necessary in cases involving prolonged or fluctuating symptoms, particularly during longer courses of combined antibiotic treatment, when monitoring of liver function, kidney function and haematological parameters is essential.
One of the most common sources of error in the follow-up of Lyme disease is the overinterpretation of serological results. Following successful treatment, Borrelia-specific IgG antibodies often remain detectable for years, and in some cases for life. For this reason, a positive serological result does not in itself prove active infection and cannot be regarded as evidence of treatment failure. Indeed, the destruction of Borrelia bacteria may promote the development of an immune response, so a strong IgG response may be an expected outcome following successful treatment. In their long-term follow-up study, Hammers-Berggren and colleagues demonstrated that both IgM and IgG antibodies can persist for months or even years following successful treatment. Lomholt and his team reached a similar conclusion: a significant proportion of treated patients remained IgG-positive even after 9–10 years, despite having been clinically cured.
These data are particularly important for clinical decision-making, as overuse of routine serological monitoring can easily be misleading. According to international guidelines, the success of treatment should primarily be assessed on the basis of clinical criteria, and serological monitoring is only justified in specific cases. The Lyme disease guidelines of the French professional societies clearly state that routine serological follow-up is not recommended, as the persistence of the antibody response does not reliably correlate with active infection.
However, in certain cases, serological trends may nevertheless provide additional information. In their study, Wahlberg and colleagues found that following successful treatment, IgG antibody titres showed a significant decrease within 6–12 months, and in patients whose titre fell below 30% of the original value, a clinically successful therapeutic response was observed in every case. However, this does not mean that persistently high antibody levels automatically confirm active infection; rather, they should be interpreted as a supplementary element of the clinical picture.
The role of PCR tests in follow-up remains limited. Although molecular diagnostic methods can detect Borrelia genetic material in certain samples – such as cerebrospinal fluid or synovial fluid – a negative PCR result does not rule out infection, and a positive result does not necessarily indicate the presence of a live pathogen. However, Oksi and colleagues reported several cases of positive PCR results and Borrelia presence confirmed by culture following treatment during clinical relapse in disseminated Lyme borreliosis. This suggests that clinical re-evaluation may be warranted in patients presenting with persistent or recurrent symptoms, particularly where objective neurological, joint or systemic abnormalities are also present.
In recent years, increasing attention has been directed towards diagnostic methods based on direct pathogen detection. The technology used by DualDur is not aimed at the immune response, but at the direct detection of the Borrelia pathogen itself from a blood sample. The advantage of this method is that it may be able to identify the infection even before seroconversion, and can provide information in cases where traditional serological tests are difficult to interpret. Direct tests with such clinical relevance are particularly suitable for determining the success of treatment. The method has been validated by one of Europe’s largest clinical trials on Lyme disease diagnosis, and the test is based on direct microscopic detection of the pathogen.
The role of such direct tests in follow-up may be of particular interest in patients whose clinical symptoms persist or recur after treatment, whilst conventional serological results do not provide a clear answer.
Follow-up requires particular care in cases of neurological involvement in Lyme disease. The regression of neurological symptoms is often slower than the microbiological control of the infection. A decrease in cerebrospinal fluid cell count and normalisation of inflammatory parameters may indicate a favourable therapeutic response; however, intrathecal antibody production may persist for years. For this reason, repeated CSF testing should be avoided and is only recommended on clinical indication, for example in the case of progressive neurological symptoms or therapeutic uncertainty.
Prolonged recovery is also observed in Lyme arthritis. Joint swelling and pain may persist for months even after appropriate antibiotic therapy. During follow-up, it is therefore particularly important to assess objective signs of inflammation and to distinguish whether the condition is an active infection or a predominantly immune-mediated process. If symptoms persist or worsen, it may be necessary to reconsider the treatment strategy, in conjunction with further microbiological tests and differential diagnostic analysis.
When monitoring Lyme disease, the possibility of co-infections must always be considered. The presence of Babesia, Bartonella or other tick-borne infections can significantly influence the patient’s condition and the assessment of the therapeutic response. Furthermore, persistent symptoms may also be caused by autoimmune, endocrinological, neurological or psychiatric conditions; therefore, an approach focused exclusively on Lyme disease can easily lead to a diagnostic dead end.
The aim of follow-up is therefore not merely to determine whether the infection has ‘disappeared’, but to assess the patient’s overall functional status. In many cases, successful treatment is not measured by a single laboratory result, but by the gradual improvement in exercise tolerance, neurocognitive function, sleep quality and quality of life. Properly structured follow-up examinations therefore play a fundamental role in ensuring that the treatment of Lyme disease is truly effective and sustainable in the long term.
Sources
- https://lymenet.hu/wp-content/uploads/2023/04/Orvosi-Hetilap-Lyme-therapia.pdf
- https://dualdur.com/
- PubMed – Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis
- PubMed – Long-term serological follow-up of patients treated for chronic cutaneous borreliosis
- PubMed – Treatment of late Lyme borreliosis
- PubMed – Borrelia burgdorferi detected by culture and PCR in clinical relapse
- PubMed – French scientific societies’ Lyme guidelines
(C) Lyme Borreliosis Foundation
