Chronic fatigue syndrome: what are its causes and symptoms + Diagnostics

Patients with this diagnosis suffer from severe fatigue, slowed and impaired thinking, sleep problems, and hormone dysregulation. There is also nausea after exertion, which can seriously impair the patient's ability to perform activities of daily living.

Early diagnosis and early treatment are crucial to prevent the high incidence of this disease and its negative impact on quality of life.

Chronic fatigue syndrome, also called myalgic encephalomyelitis, is a complex multisystem disease. In addition to the nervous system, it also affects the hormonal system, immunity, psyche and others.

The prevalence of the disease is significantly higher in the 40 to 70 age group, but children, adolescents or young adults in their 20s can also become ill.

Interestingly, nurses are often affected.

It is more often diagnosed in the white population. Studies have also shown that it is more common in the low-income group than in the higher income and higher education group. This points to the important role of social risk factors such as stress.

The disease is progressive, meaning that its symptoms worsen if left undiagnosed or inadequately treated for years.

The syndrome occurs even in animals and is 50% fatal. In humans, it is very rare.

The causes of chronic fatigue syndrome are a controversial topic among experts, because the syndrome is too complicated and still not fully understood.

Currently, the most important reasons for the onset of the disease are considered to be infection with certain infectious diseases, dysregulation of the immune system and genetic disorders.

Genetics

Evidence for the involvement of genetics is the fact that the disease very often occurs in patients with a family history of the syndrome. If it has manifested in a parent, there is a high risk that a child or sibling will also suffer from it.

There are also specific genetic mutations known to be present in the genome of patients with the disease.

Infection

Various infectious diseases are thought to be the trigger for the disease.

Known causes include infection with Epstein-Barr virus (EBV), human herpesvirus (HHV)-6 and human parvovirus B19.

Exposure to diseases such as infectious mononucleosis, frequent herpes, B19 viremia, or the so-called fifth childhood disease can trigger the onset of chronic fatigue syndrome.

Changes in the immune system

These are mainly changes in B-lymphocyte levels.

In addition, increased levels of IgG immunoglobulins (antibodies produced by B-lymphocytes) have been observed.

Some patients also have specific autoantibodies, which are antibodies directed against their own tissues.

These are antibodies against the nuclear and membrane structures of cells and antibodies against neurotransmitter receptors. These are chemicals that are responsible for the transmission of information in the nervous system.

These changes cause chronic inflammation in the body, activation of oxidative stress in the body, changes in neuroendocrine function and autoimmune attack against neurons.

Specifically, these include antinuclear antibodies (ANA), anti-dsDNA antibodies and antibodies against neuronal and endothelial cells.

Increased oxidative stress

Patients with chronic fatigue syndrome have a significant increase in oxidative stress, which plays a major role in the flare-up of the disease.

There is an increase in biomarkers of oxidative stress, such as oxidised LDL cholesterol ('bad cholesterol'), and some prostaglandins. At the same time, there is a decrease in positive antioxidants, such as naturally occurring glutathione.

Oxidative damage converts fatty acids and proteins into targets for autoimmune processes.

Free radicals produced by chemical reactions in the human body damage the chain of transport of important substances as well as energy production. Finally, they cause damage to the mitochondria, which are important organelles through which the cell breathes.

Changes in serotonin transmission

Fatigue, which is a key symptom in patients with this chronic fatigue syndrome, is thought to be caused by excessive levels of serotonin and its metabolites in the central nervous system.

Excess serotonin leads to impaired action potential generation (the starter of neural responses) and thus to reduced motor activity.

Hypocortisolism

Cortisol (hydrocortisone) is a steroid hormone. It is naturally produced in the human body, specifically in the adrenal glands. The secretion of the hormone from the adrenal glands is regulated by the hypothalamic-pituitary axis.

Its main function is to increase the body's overall alertness and readiness for stressful situations such as stress or infections.

In patients with chronic fatigue syndrome, the hypothalamic-pituitary axis is impaired and therefore circulating cortisol levels are too low.

It is the low level of this hormone that causes one of the leading manifestations of chronic fatigue syndrome, namely nausea after physical exertion.

The characteristic symptom is fatigue after exertion associated with many neurological, cardiovascular, respiratory and gastrointestinal problems.

The fatigue described by patients is exacerbated by physical exertion and upright or stiff posture, for example, when sitting for long periods at work at a computer.

Fatigue is not alleviated by rest and no other medical reason can be found for it, i.e. other illnesses accompanied by fatigue (infectious diseases, inflammation, cancer, etc.).

Patients often report that they were in very good condition before the onset of fatigue. They describe a sudden onset of fatigue, usually associated with a flu-like illness.

They also experience nausea after exertion. Regular physical activity is followed by nausea and fatigue with a long recovery period, usually lasting more than one day.

New-onset chronic headaches with various irregular fluctuations are also common. Muscle pain is most common in paediatric patients and may also be a symptom of an associated disease, fibromyalgia.

Joint pain is due to an associated autoimmune disease, rheumatoid arthritis.

Sleep is disturbed by frequent awakenings and is not refreshing. Therefore, patients experience diurnal hypersomnolence, i.e. the need for daytime napping, especially in the afternoon, and nocturnal insomnia.

Slowed thinking, impaired mental processing, poor ability to learn new things, impaired processing of new information, memory decline, reduced attention span, and inability to perform multiple tasks at once are symptoms for which most of these patients have a reduced ability to work.

In addition, these patients may also experience vegetative symptoms, including nausea, vomiting, night sweats, dizziness, and intolerance to alcohol and other drugs.

Psychiatric changes such as symptoms of uncontrolled anxiety, panic attacks and impaired social functioning are also common.

Chronic fatigue syndrome is diagnosed per exclusion, i.e. on the basis of clinical examination and after excluding other possible diseases.

Initially, when the cause of the disease was thought to be mainly viruses, the Centre for Disease Control and Prevention in the USA came up with criteria for diagnosis in 1988, focusing on physical symptoms.

Later, the Oxford Criteria were developed in 1991. They defined the diagnosis of chronic fatigue syndrome as a disease in which moderate to severe symptoms of fatigue, myalgia and exhaustion are present.

The Oxford criteria considered fatigue to be the primary symptom. It should have a definite onset, be severe to debilitating and affect mental and physical health.

These symptoms should be present for at least six months and should interfere with the patient's life more than fifty percent of the time.

Other symptoms such as myalgia (muscle pain), impaired mood and sleep disturbances should also be present.

The criteria exclude people with a medical condition known to cause fatigue. They also exclude people with a known mental health disorder such as schizophrenia, mania, depression, eating disorders, substance abuse or a known organic brain pathology such as a tumour.

In 2015, the Institute of Medicine (IOM) came up with new criteria for diagnosing chronic fatigue syndrome.

2015 IOM diagnostic criteria

Diagnosis requires the presence of the following three symptoms for more than six months. Further, the intensity of symptoms should be moderate or severe in at least 50% of fatigue attacks.

The three main symptoms are:

• Fatigue - characterised as a significant reduction or impairment in the patient's ability to engage in activities enjoyed before the onset of illness. This condition lasts for more than six months.

• Post-exertional malaise - patients experience a worsening of symptoms and body function after exposure to physical or psychological stressors that they previously tolerated well.

• Unrefreshing sleep - patients feel that they are still tired after a night's sleep.

A proper diagnosis requires the three symptoms listed above, plus one of the other symptoms listed below:

• Cognitive impairment - problems with thinking, memory or mental performance. The condition is exacerbated by mental strain, physical exertion, stress or time pressure.

• Orthostatic intolerance - worsening of symptoms when assuming and maintaining an upright position. Symptoms are not improved by lying down or lifting the feet.

The diagnostic process should begin with a history and physical examination. Physicians should use a validated clinical questionnaire such as the DePaul Symptom Questionnaire.

There are no laboratory diagnostic tests or biomarkers to confirm the diagnosis.

Laboratory tests are used to rule out other diseases and include urinalysis, complete blood count with differential, blood biochemistry, thyroid function tests, muscle enzyme levels such as creatine kinase, and C-reactive protein (CRP) levels.

In addition to these, gluten sensitivity tests, endomysial immunoglobulin A antibodies, urine drug screening, and rheumatologic antibody detection are also recommended.

Other appropriate tests include:

• blood pressure monitoring, pulse, ECG
• haematological examination (erythrocyte sedimentation rate, blood count, total leukocyte count and differential budget)
• microbiological examinations such as nasal and nasopharyngeal mucosal swabs, stool, urine, parasite testing
• serological investigations (antibodies to EBV, CMV, toxoplasma parasite, Borrelia, chlamydia, mycoplasma and hepatitis viruses HAV, HBV and HCV and HIV are monitored)
• immunological testing
• allergy skin tests
• spirometric lung function tests
• general neurological examination including EMG and EEG
• psychiatric and psychological sessions

Chronic Fatigue Syndrome is not a disease in the true sense of the word, but just a set of symptoms and problems that do not yet have a precise cause.

The onset of the disease can be sudden, after an infection, after a difficult life situation, after psychological stress. Some patients even report a gradual and creeping onset and cannot remember the starting stimulus of their fatigue.

Unfortunately, the illness does not last for a week, but for several months. To diagnose chronic fatigue syndrome, the symptoms need to last for at least half a year.

Many patients cannot get rid of fatigue for several years and it accompanies them throughout their lives.