From the Guidelines
Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a multisystem neuroimmune illness that often follows a viral or bacterial infection, with a substantial reduction in the ability to engage in pre-illness levels of activities, accompanied by profound fatigue, postexertional malaise, unrefreshing sleep, and cognitive impairment or orthostatic intolerance 1. The exact cause of CFS/ME remains unknown, but current research suggests it likely results from a combination of factors, including viral infections, such as Epstein-Barr virus, Coxiella burnetii, Ross River virus, and West Nile virus, as well as immune system abnormalities, with evidence of chronic inflammation and altered immune responses in affected individuals 1. Some key findings in CFS/ME include:
- Diminished natural killer cell function, T cell exhaustion, and other T cell abnormalities 1
- Mitochondrial dysfunction, vascular and endothelial abnormalities, including deformed red blood cells and reduced blood volume 1
- Exercise intolerance, impaired oxygen consumption, and a reduced anaerobic threshold, as well as abnormal metabolic profiles 1
- Altered neurological functions, including neuroinflammation, reduced cerebral blood flow, brainstem abnormalities, and elevated ventricular lactate level 1
- Reactivated herpesviruses, such as EBV, HHV-6, HHV-7, and human cytomegalovirus, are also associated with CFS/ME 1. Many of these findings have been observed in long COVID studies, suggesting a possible link between the two conditions 1. Overall, while the exact cause of CFS/ME remains unknown, research suggests that it is a complex condition involving multiple factors, including viral infections, immune system abnormalities, and neurological dysfunction 1.
From the Research
Causes of Chronic Fatigue Syndrome
The exact causes of chronic fatigue syndrome (CFS) are still not fully understood, but several potential factors have been identified:
- Dysfunction of the autoimmune, neuroendocrine, or autonomic nervous systems may contribute to the development of CFS 2
- Infections, such as Epstein Barr virus (EBV), may trigger the onset of CFS, although it is not always preceded by such infections 2
- Immune dysregulation, including decreased natural killer cell and macrophage activity, and immunoglobulin G subclass deficiencies, may play a role in the pathogenesis of CFS 3
- Autoantibodies, such as anti-serotonin, anti-microtubule-associated protein 2, and anti-muscarinic cholinergic receptor 1, may also be involved in the development of CFS 3
- Impairment in vasoactive neuropeptide metabolism may contribute to the symptoms of CFS 3
- Genetic and epigenetic factors may influence an individual's risk of developing CFS, although more research is needed to fully understand their role 4
Potential Triggers
Several potential triggers for CFS have been identified, including:
- Infections, such as EBV 2
- Physical or emotional stress 5
- Autoimmune disorders 2
- Hormonal imbalances 2
- Sleep disturbances 6
Complexity of CFS
CFS is a complex and multifaceted illness, and its causes are likely to be equally complex:
- CFS may be the result of a combination of genetic, environmental, and psychological factors 4
- The condition may be influenced by a range of biological, psychological, and social factors, including immune function, hormone regulation, and lifestyle 2, 5
- More research is needed to fully understand the causes of CFS and to develop effective treatments 2, 6, 4, 3