Introduction

What is chronic fatigue syndrome?

Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is a long-term health condition that causes an array of complex and often debilitating symptoms. 

CFS/ME is a poorly understood condition with many symptoms and causes that vary between patients. This means it can be hard for healthcare professionals to pinpoint the condition and make an accurate and timely diagnosis. The consequence of this is delayed treatment and potential impairment of a patient’s ability to carry out everyday activities.

Therefore, we need to understand the symptoms and causes of CFS/ME so that cases can be promptly recognised and patients can maximise their quality of life.

How is fatigue different from tiredness?

It is common for everyone to feel tired from time to time. Tiredness that is persistent, and isn’t relieved by sufficient sleep and rest, is generally described as fatigue.¹ 

Symptoms of CFS/ME

CFS/ME is a multisystemic disorder and causes a range of symptoms that affect many parts of the body.

Primary symptoms

Persistent fatigue

This is the most commonly reported symptom. Fatigue is not relieved by rest and has no other medical cause. You may also find that your fatigue is exacerbated by prolonged standing, and simple everyday activities may rapidly deplete your energy levels.

Post-exertional malaise (PEM)

PEM is defined as a worsening of symptoms following regular activity. You may need to recover for at least 24 hours before being able to return to your normal level of activity. Periods of PEM are sometimes referred to as a ‘crash’. 

Unrefreshing sleep

Sleep disturbances and waking up feeling unrefreshed are other key symptoms of CFS/ME. Poor quality sleep may lead to you feeling drowsy during the day and then being unable to sleep again at night. This is known as sleep inversion or day/night reversal.

Secondary symptoms

Although its name suggests fatigue as the hallmark symptom, CFS/ME can cause a much wider array of problems.

Cognitive impairment

You may notice the following symptoms, which are collectively termed ‘brain fog’:

• Struggling to learn and retain new information
• Being unable to retrieve words easily
• Getting distracted easily or finding it hard to concentrate on a task
• Having a slow mental processing speed
• Noticing a decline or impairment in your memory

Muscle and joint pain

Fibromyalgia is a common comorbidity of CFS/ME. If you suffer from joint pain, it is possible that you could also fit the diagnostic criteria for conditions such as rheumatoid arthritis or systemic lupus erythematosus.

Headaches

New-onset headaches are common and tend to fluctuate in severity. If you experience these regularly, your doctor may consider a migraine diagnosis. 

Psychiatric symptoms

It is common to experience psychiatric disorders, such as major depressive disorder and generalised anxiety disorder.

Autonomic symptoms

As part of CFS/ME, you may notice symptoms of dysautonomia. One such type is postural orthostatic tachycardia syndrome (POTS), which is characterised by orthostatic hypotension. This is a sudden drop in blood pressure that occurs upon sitting or standing up. As a result, you could experience heart palpitations, and feel dizzy and lightheaded.

Other features associated with dysautonomia include:

• Exercise intolerance – you may find it hard to participate in high-intensity activity due to a worsening of dizziness and fatigue
• Unable to regulate body temperature – you may feel cold easily or sweat abnormally
• Alcohol intolerance – alcohol causes your blood vessels to dilate so exacerbates dizziness
• Digestive symptoms – you may experience nausea and other general symptoms associated with comorbidities of CFS/ME, such as irritable bowel syndrome (IBS)

Neuroendocrine symptoms

Some patients with CFS/ME report feeling constantly feverish due to problems with their endocrine system. You may also experience loss of appetite and have a lower tolerance for stress and anxiety. 

Immune dysfunction

Symptoms related to this include sore throat, swollen lymph glands and sensitivities to certain foods or medications.^1,2,3

Causes of CFS/ME

There are many suggested causes, both environmental and biological, that are associated with the onset of CFS/ME. 

Environmental causes

Viral infections

The Epstein-Barr virus is the main infectious cause of CFS/ME. It causes glandular fever, and if you contract this illness you may continue to suffer from symptoms even after the virus has cleared from your body; these prolonged symptoms may lead to a diagnosis of CFS/ME.

Slapped cheek syndrome, which occurs upon infection with the human parvovirus B19, is also believed to be a cause of CFS/ME. This is particularly common in children and could explain the cause of paediatric cases of CFS/ME.

Exposure to toxins

Some cases of CFS/ME may be attributed to environmental toxins, including heavy metals, pesticides, industrial chemicals or mycotoxins. When these toxins are ingested, an immune response is generated that could lead to the development of CFS/ME symptoms.⁴ 

Biological causes

Alterations in the immune system

It has been suggested that CFS/ME is caused by a change in a person's immune system and how it responds to infection or stress.

If you’ve ever contracted a viral illness, such as the common cold, you’ll be familiar with the unpleasant sore throat, body aches, and blocked or runny nose that accompany the illness. You experience these symptoms because the virus, otherwise known as an antigen, triggers your immune system to produce antibodies to help you fight the infection.

In CFS/ME, it is thought that patients struggle to elicit this immune response owing to the malfunctioning of various immune cells. Examples of this include:

• Decreased function of natural killer cells – these are a type of white blood cell that act as a first line defence for controlling the invading antigen
• Decreased receptor response of T cells to specific antigens – T cells are another type of white blood cell with a receptor on their surface that binds to antigens, causing the T cell to become activated and an immune response to be triggered

The consequence of this is a lower functional ability to fight infections. You may also find that you take longer to recover from mild infections. 

Inflammation

It has also been reported that CFS/ME may cause inflammation in the body due to raised levels of proteins in the immune system known as cytokines. These molecules are released during the normal immune response to an antigen, causing you to feel achy and feverish. In CFS/ME, it is thought that a person’s immune system is overactivated which explains why you might feel like you’re constantly suffering from a cold or the flu. 

Should CFS/ME be considered an autoimmune condition?

Autoimmune conditions occur when your immune system mistakenly identifies healthy cells as foreign and attacks these cells, resulting in various unwanted symptoms.

Studies have identified autoantibodies which are targeted against components of the central nervous system, like neurotransmitter receptors. This autoimmune-like behaviour could provide evidence that CFS/ME should be classed as this sort of condition.

Alterations in the central nervous system

Increased neuroinflammation may be an underlying cause of CFS/ME. Constant activation of inflammatory molecules in the central nervous system can cause pain, a common complaint in CFS/ME. Patients typically have an exaggerated response to painful stimuli as well as a reduced threshold for pain.

Neuroinflammation is also known to disturb the release of a type of neurotransmitter called serotonin which contributes to making us feel good. When levels of serotonin are low, we see an onset of the psychiatric symptoms associated with CFS/ME, including depression and anxiety.^1,2,3

Alterations in the neuroendocrine system

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are consistent with CFS/ME. The HPA axis is responsible for controlling your body’s reaction to stress via the hypothalamus and pituitary gland in the brain, and the adrenal glands near the kidneys. Certain hormones, like cortisol, are released from these glands and when this is disrupted, body functions, like the immune response, can be affected. Cortisol functions to lower inflammation so reduced levels of this hormone could lead to increased inflammation and an onset of CFS/ME.⁵

Genetic predisposition

Finally, twin studies have shown that there could be a possible hereditary link in CFS/ME. The results of one such study revealed familial aggregation in some of the 146 female-female twin pairs included in the research.⁶ 

Summary

• CFS/ME is a chronic, multisystemic disorder with fatigue as its hallmark symptom
• You may also experience sleep disturbances, brain fog, pain, and dysautonomia
• Glandular fever, which is caused by the Epstein-Barr virus, typically precedes a diagnosis of CFS/ME, although environmental toxins play a role in the onset of the condition too
• Immunological, central nervous system and neuroendocrine changes may also contribute to CFS/ME
• Sometimes the cause of CFS/ME is unknown. This can make a timely diagnosis difficult to achieve so improved physician awareness is needed so that suspected cases of the condition can be identified quickly and treatment promptly implemented to ensure the best possible recovery for the patient