There is no single diagnostic test that is standard for everyone, so diagnosis may be based on a detailed assessment of symptoms.
Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a complex, long-lasting condition characterised by persistent and debilitating fatigue that cannot be explained by any other illness or condition. The fatigue lasts for at least six months and is not relieved by rest, but often worsens after physical or mental exertion – this is called post-exertional malaise (PEM). Symptoms may also include concentration and memory problems (“brain fog”), sleep disturbances, muscle and joint pain, headaches, sore throat, swollen lymph nodes, and sensitivity to light or noise.
The exact cause of CFS is unknown, but research is investigating several possible factors: conditions caused by or following infections (such as the link to Lyme disease), immune system disorders, hormonal abnormalities, and psychological stress. In some cases, the illness begins after a flu-like infection, while in others it develops gradually. There is no single diagnostic test that works for everyone, so diagnosis is based on a detailed assessment of symptoms, ruling out other illnesses, and internationally accepted criteria. The course of the disease varies: some patients recover partially, while others live with a significant deterioration in their quality of life for many years. CFS affects millions of people worldwide and can have a serious impact on daily life, work capacity and social relationships, so early detection and complex treatment are of paramount importance.
The link between chronic fatigue syndrome and Lyme disease has been investigated in numerous studies, which have found significant correlations.
According to a classic study by Gaudino and colleagues, there are significant similarities in symptoms between chronic fatigue following Lyme infection (post-Lyme fatigue, sometimes referred to as “post-Lyme syndrome”) and ME/CFS. The authors used psychiatric and neuropsychological tests on patients diagnosed with CFS and patients diagnosed with Lyme disease who reported persistent fatigue. They emphasised that although fatigue, cognitive problems and mood disorders occurred in both groups, Lyme disease patients often showed more severe impairment in attention, memory and motor performance.
Another study showed that healthy young men who tested positive for Lyme antibodies, even though they had never been diagnosed with clinical Lyme disease, reported chronic fatigue and malaise more frequently than seronegative men. This suggests that Lyme disease itself may be associated with chronic fatigue.
A similar phenomenon was already described in the late 1980s, and in 1993, Steere and colleagues also found high rates of CFS or fibromyalgia in patients who tested positive for Lyme disease in other laboratories but were seronegative in the authors’ laboratory.
A study examining different but partially overlapping patient groups (with a history of Lyme disease, post-COVID and CFS) found that orthostatic hypotension and reduced heart rate variability were particularly common among patients with a history of Lyme disease, indicating involvement of the autonomic nervous system. The late stage of Lyme disease is primarily characterised by adrenergic dysfunction and specific haemodynamic responses, which can distinguish it from other post-infectious syndromes. Detailed examination of autonomic function can contribute to a more accurate diagnosis and the development of targeted therapeutic strategies.
The use of correct terminology and reasonable examination of the conclusions that can be drawn from the data are very important for the diagnosis of chronic fatigue. Numerous professional articles dealing with this symptom complex mention the terms post-Lyme or Post Treatment Lyme Disease Syndrome (PTLDS). Although these articles describe well-defined clinical pictures, these terms are actually scientifically poorly defined. They are most commonly used in cases where the patient has been clinically or serologically diagnosed with Lyme disease and has received the treatment permitted/prescribed/recommended in the country concerned, but Lyme symptoms persist for more than 6 months after treatment. Given that the serological picture after treatment is not relevant with the serological tests commonly used (there is no negative “clearing” finding, although conclusions can be drawn from a detailed analysis of the immune response), most authors assume that the treatment was necessarily effective. As a result, the symptoms can no longer be symptoms of Lyme disease, which is why the concept of PTLDS was introduced. Logically, there is no definition of this condition that has been confirmed by proper medical examination, as the presence of live pathogens or the successful elimination of pathogens cannot be verified except by direct laboratory tests, and these have not been used in any PTLDS research. However, it has been confirmed that, especially in the case of short, 2-4 week monotherapies, the pathogen or its various proteins and genome can still be detected months after treatment, which is evidence of the persistence of the live pathogen and thus the failure of the therapy.
As a result, in patients previously diagnosed with Lyme disease, whether treated or untreated, it is reasonable to test for the presence of the pathogen or, in the absence of direct testing, to assume that the presence/recurrence of Lyme disease may be behind CFS if clinical Lyme symptoms are present. In addition, even if no other Lyme symptoms are present beyond the CFS symptom complex, according to some extensive studies, antibiotic treatment may still be considered, given the close overlap between the neurological symptoms of CFS and Lyme disease.
In summary, from a clinical, neuropsychiatric and functional perspective, there are significant overlaps between (severe, long-term) fatigue following Lyme disease and ME/CFS, particularly in terms of fatigue, cognitive difficulties, non-restorative sleep and post-exertional malaise. Further genetic and biological research holds promise for the development of more specific biomarkers and targeted therapies in the future, whether for conditions with a history of Lyme disease or ME/CFS-like conditions.
Sources:
https://pubmed.ncbi.nlm.nih.gov/10686469/
https://pubmed.ncbi.nlm.nih.gov/26270685/
https://pubmed.ncbi.nlm.nih.gov/40002769/
https://pubmed.ncbi.nlm.nih.gov/39994562/
(C) Lyme Borreliosis Foundation
