Lyme disease, an infection caused by the Borrelia burgdorferi spirochete bacterium, is the most common vector-borne disease in Europe. It is common in Hungary and other temperate climates, with new infections occurring particularly from spring to autumn, when ticks are most active. Lyme infection can cause a variety of symptoms, including fatigue and lethargy, which are often one of the first complaints.
Fatigue may occur during the acute phase of the disease, but in some cases it may persist for a long time after treatment. It is important to note that most of the symptoms that remain after treatment may be due to the use of inappropriate antibiotics or antibiotics that are not used for a sufficient period of time. Unfortunately, however, the presence of the pathogen is not tested after treatment, even though the bacterium (or part of it) could be detected by direct diagnostic methods, and a negative result would confirm the destruction of the pathogens. It should not be assumed that if the patient has received treatment, it was effective in all cases and that a recurrence of Lyme disease or reinfection can be ruled out. It should therefore not be taken for granted that after the presumed completion of Lyme disease, the symptoms can only be due to another condition, so it is not recommended to use the term PTLDS (= post-treatment Lyme syndrome), whose medical definition is dubious and can be extremely misleading. This approach has given rise to the famous phrases used by doctors to describe the neurological, less tangible symptoms of Lyme disease, such as fatigue: “it’s all in your head”.
In acute Lyme disease, fatigue – often accompanied by flu-like symptoms – is almost universal. However, after treatment, the symptoms resolve in many people. Prospective studies show that in the long term – years later – properly treated Lyme disease rarely results in severe fatigue.
In an 11-20 year follow-up study, out of 100 patients diagnosed with Lyme disease based on erythema migrans, only 9% experienced severe fatigue on an objective scale (Fatigue Severity Scale–11), only 9% experienced severe fatigue, and only 3% of patients experienced mild fatigue, which may have been related to the disease, but did not cause functional impairment.
A comprehensive review highlights that non-specific symptoms associated with Lyme disease, such as fatigue, cognitive slowing and headaches, do not indicate proven neurological infection or permanent damage. These are often balanced and usually resolve, although sometimes it takes longer.
There may be several mechanisms behind fatigue during or after Lyme disease. A more detailed examination suggests that the following may be involved:
- Post-infectious fatigue syndrome: a mechanism similar to that seen after other infections, where symptoms may persist in a chronic form depending on the severity of the acute phase – for example, in one study, the incidence of fatigue was 35% within 6 weeks after infection, 27% 3 months later, and 9% 12 months later. There are no data on how much of this was caused by Lyme disease that persisted despite treatment.
- Autoimmune or inflammatory reactions: One possible explanation for the fatigue associated with Lyme disease is that the infection may trigger autoimmune processes. The surface proteins of Borrelia burgdorferi (e.g. OspA) show structural similarities to certain human proteins, so T-cell activity against the pathogen may cross-react with its own antigens – this is called molecular mimicry. A proven example is Hashimoto’s thyroiditis as a result of Lyme disease, which can affect fatigue and mood through changes in thyroid hormones. Clinical studies have shown that the presence of certain HLA-DR alleles (e.g. DRB1*0401) increases the likelihood of a cross-reactive immune response and prolonged inflammation, especially in the joints. At the same time, the strong inflammatory cytokine profile (e.g. IFN-γ, TNF-α, IL-17) measured in the early stages of the disease indicates persistent immune activation, which may also contribute to the development and persistence of fatigue through central nervous system mechanisms. Overall, the immunological consequences of Lyme disease – particularly cross-reactive T cells and inflammatory cytokines – provide a biological basis for the infection to cause persistent fatigue in some patients.
- Deterioration in sleep quality: Sleep quality is also closely related to feelings of fatigue. According to one study, Lyme disease patients often complain of poor sleep, and tests have shown that polysomnography indicators also differ from those of healthy controls: their sleep is characterised by longer onset latency, lower sleep efficiency and frequent awakenings.
- Autonomic nervous system dysfunction:
Nerve damage in Lyme disease often leads to small fibre neuropathy, which can also affect the autonomic nervous system. This results in disturbances in heart rate and blood pressure regulation, orthostatic intolerance, and reduced cerebral blood flow. These disorders contribute to fatigue, difficulty concentrating and symptoms of “brain fog”. - Mitochondrial and metabolic disorders:
The immune and inflammatory processes triggered by the infection can also significantly affect metabolism. Metabolomic studies have found abnormalities in lipid and amino acid metabolism, as well as signs of oxidative stress. These changes impair mitochondrial efficiency, which means less energy for cells, and can manifest as persistent fatigue and reduced exercise capacity. - Neurocognitive changes:
Cognitive tests and imaging studies have shown that certain areas of the brain, particularly the frontal regions, function less efficiently in Lyme disease patients. This results in slower information processing, memory impairment and increased mental effort, which can lead to cognitive fatigue and general exhaustion.
Fatigue in Lyme disease is not only related to physical exhaustion, but is often associated with various cognitive complaints (such as memory impairment and slowed thinking) – according to patient reports, but these can also be detected in objective tests, even in the absence of depression or anxiety.
In summary, the relationship between Lyme disease and fatigue is complex and multifaceted. Fatigue often occurs in acute Lyme disease, as with other infections, and although it usually decreases after treatment, some patients may experience prolonged weakness, lethargy and difficulty concentrating.
Possible explanations include post-infectious inflammation, autoimmune reactions, sleep disturbances, autonomic nervous system dysfunction, mitochondrial/brain metabolism disorders, and neurocognitive changes. However, in most cases, these symptoms improve over time, and it is rare for chronic, severe fatigue to persist in association with properly treated Lyme disease.
From a clinical point of view, thorough investigation is essential: in cases of sudden fatigue, Lyme disease should always be considered, but other psychological, sleep-related or somatic causes must also be assessed. An integrated approach – including sleep diagnostics, autonomic function testing, immunological and metabolic parameters – can contribute to a more accurate diagnosis and targeted support.
Sources:
https://pubmed.ncbi.nlm.nih.gov/25447620/
https://pubmed.ncbi.nlm.nih.gov/26028977/
https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.00464/full
https://www.sciencedirect.com/science/article/abs/pii/S0891552007001274?via%3Dihub
https://pubmed.ncbi.nlm.nih.gov/16585267/
https://pubmed.ncbi.nlm.nih.gov/11290815/
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1344862/full
(C) Lyme Borreliosis Foundation
