Chronic fatigue syndrome

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chronic fatigue syndrome

Chronic fatigue syndrome

Chronic fatigue syndrome also called CFS, myalgic encephalomyelitis (ME), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or systemic exertion intolerance disease (SEID) is a complex multisystem condition that causes you to feel tired, fatigue and exhausted that lasts 6 months or longer 1, 2, 3, 4, 5. In some cases, CFS can last for years. Your fatigue doesn’t improve with rest or sleep and gets worse after physical activity or mental exertion. Chronic fatigue syndrome can prevent you from completing your daily routine or getting out of bed. In addition, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can cause difficulty sleeping (falling or staying asleep), problems with thinking, attention, concentration and memory, worsening of symptoms while standing or sitting upright called orthostatic intolerance, headaches and joint and muscle pain.

Chronic fatigue syndrome symptoms vary widely from person to person.

The primary, or core, symptoms of chronic fatigue syndrome (CFS) are 6:

  • Not being able to do activities that you used to do before the illness, along with severe fatigue. The fatigue must last six months or longer, and it is not improved by rest or sleep.
  • Post-exertional malaise, which means that your symptoms get worse after any physical or mental activity. Post-exertional malaise usually begins within 12 to 24 hours after your activity, and it can last for days or weeks. People who have post-exertional malaise often struggle to find a good balance between activity and rest. The goal is to remain active without overdoing it. This is also called pacing or activity management. The goal is to learn to balance rest and activity to avoid flare-ups. These can be caused by exertion that patients cannot tolerate.
  • Difficulty sleeping (falling or staying asleep).
  • Problems with thinking, attention, concentration and memory.
  • Worsening of symptoms while standing or sitting upright, this is called orthostatic intolerance. It can cause you to feel lightheaded, dizzy, weak, or faint while standing or sitting up.

People who have chronic fatigue syndrome may also experience the following symptoms 7:

  • Fatigue.
  • Headaches.
  • Sore throat.
  • Tender or painful areas in your neck or armpits due to swollen lymph nodes or lymph glands.
  • Muscle soreness.
  • Pain, including muscle pain, joint pain, and headaches.
  • Joint pain that moves from joint to joint without swelling or redness.
  • Loss of memory or concentration.
  • Trouble sleeping.
  • Digestive issues, like irritable bowel syndrome (IBS).
  • Chills and night sweats.
  • Allergies and sensitivities to foods, odors, chemicals, light, or noise.
  • Extreme tiredness after exercising that lasts more than 24 hours.

These and other symptoms often won’t go away or keep coming back for 6 months or more.

It’s also common for people who have ME/CFS to also have other health problems at the same time, such as sleep disorders, irritable bowel syndrome (IBS) or fibromyalgia. In fact, there are so many overlapping symptoms between chronic fatigue syndrome and fibromyalgia that some researchers consider the two disorders to be different aspects of the same disease.

Chronic fatigue syndrome affects an estimated 836,000 to 3.3 million people in the United States 8, 9, 10, 11, 12, 13, 14, 15, 16. As per the study conducted by Bierl and colleagues in 2004 17, about 1,197 people per 100,000 suffer from CSF and CFS-like illnesses in the United States. A meta-analysis showed that the overall incidence of CFS is 0.77% and 0.76% in Korea and Japan, respectively 18.

About 90% of people who experience chronic fatigue syndrome don’t receive a diagnosis even though they live with this condition. The main barriers that prevent people from getting a diagnosis are access to healthcare and awareness of the condition.

Scientists don’t know the exact cause of chronic fatigue syndrome (CFS) and are still looking for the cause of CFS 19, 20, 21. CFS may occur after an illness such as a cold or it can start during or shortly after a period of high stress. Chronic fatigue syndrome (CFS) can also come on slowly without any clear starting point or any obvious cause.

Research suggests there could be several factors that might lead to CFS:

  • Low blood pressure.
  • Physical or emotional trauma or stress.
  • An infection by some kind of virus or bacteria.
  • Immune system changes (how your body responds to stress or an infection).
  • Weak immune system.
  • Problems with how your body makes and uses energy.
  • There may be a genetic link to chronic fatigue syndrome. Studies found chronic fatigue syndrome can sometimes run in families. More research is necessary to determine what gene is responsible for chronic fatigue syndrome.

For unknown reasons, women are more likely to develop chronic fatigue syndrome than men 22. Furthermore, young children and teenagers can also develop chronic fatigue syndrome, but it’s much more common in adults between the ages of 40 and 70 23. The prevalence seems higher in the White population than in the non-White population 22. Studies have also reported a markedly higher chronic fatigue syndrome prevalence in the low-income cohort than in the higher-income and higher-educated cohort, suggesting the role of social risk factors such as stress in the causation of CFS 23, 17, 22. No regional differences were noticed in the country as far as CFS prevalence is concerned 17.

Chronic fatigue syndrome (CFS) is difficult to diagnose because scientists don’t know the real cause of chronic fatigue syndrome and there is no specific test for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other illnesses can cause similar symptoms. Some people have a hard time accepting CFS as a disease. The first step is to see if there is any other explainable cause for your fatigue. Your doctor will probably want to review your symptoms, medical history, your family’s medical history and doing a physical exam and mental health evaluation. Asking about your current illness, including your symptoms. Some questions your doctor may ask could include how often you have symptoms, how bad they are, how long they have lasted, and how they affect your life. Your doctor may also want to do some blood tests, but lab testing is not often helpful in the diagnosis of CFS.

It’s important to remember that your fatigue is real and that you can work with your doctor to manage your symptoms.

At the present time, because scientists don’t know the real cause of chronic fatigue syndrome, there is no cure or approved treatment for CFS, but you may be able to treat or manage some of your symptoms. Treatment can help manage symptoms with medication, sleep hygiene and activity management. Medicine can treat some of the symptoms, such as muscle aches, sleep problems, anxiety, and depression. The medicine may only reduce your symptoms and allow you to be more active, not cure the fatigue. So far, there is no medicine that cures chronic fatigue syndrome. Most symptoms improve with time. Cognitive behavioral therapy (CBT) is helpful for many people with CFS. This can help you better tolerate symptoms, thoughts and behaviors that may change through treatment.

Your doctor can work with you to provide relief from your CFS symptoms. He or she also can help you find ways of coping with the way CFS changes your life. Chronic fatigue affects you physically, emotionally, and socially. When you address all of these factors, you have the best chance of adjusting to your illness and feeling more satisfied with your life.

Chronic fatigue syndrome causes

The cause of myalgic encephalomyelitis or chronic fatigue syndrome is unknown, although there are many theories 24, 19, 20, 21. It is proposed that an alteration in your nervous system occurs secondary to your body’s immune system unintended responses to commonly encountered antigens leading to changes in the cell-mediated immunity, activation of oxidative pathways, and alteration in the neuroendocrinal and autoimmune responses against neurons 25. Multiple studies have shown alterations in the functioning of the natural killer (NK) cells, interleukins profile, and the decreased response of T cells to specific antigens 24. There is evidence of ongoing inflammation, as indicated by increased production of various proinflammatory interleukins, which also explains malaise and flu-like symptoms about which the patients often complain 24.

Experts believe chronic fatigue syndrome might be triggered by a combination of factors:

  • Infections by some kind of virus or bacteria. Some people develop myalgic encephalomyelitis or chronic fatigue syndrome symptoms after getting better from a viral or bacterial infection 26. Various virus infections  including the Epstein-Barr virus (EBV), the human herpesvirus 6 (HHV-6), and the human parvovirus B19, are hypothesized to trigger myalgic encephalomyelitis or chronic fatigue syndrome 27, 28, 29, 30.
    • Speculations are that in a few patients, the acquisition of viral infections like Epstein-Barr virus (EBV) causing infectious mononucleosis triggers the onset of chronic fatigue syndrome disease process 31, 32, 33.
    • Researchers have detected IgM antibodies to human herpesvirus 6 (anti-HHV6) and HHV-6 antigens more commonly in the peripheral blood of patients with chronic fatigue syndrome than in the general population, indicating higher prevalence and higher reactivation of the human herpesvirus 6 virus in this group of people 34, 35, 36, 37.
    • Parvovirus B19, both with and without viremia, has been implicated in developing and triggering chronic fatigue syndrome 38. These patients have higher levels of tumor necrosis factor and interferon-gamma 39.
  • Physical or emotional trauma or stress. Some people report that they experienced an injury, surgery or significant emotional stress shortly before their symptoms began.
  • Problems with how your body makes and uses energy. Some people with ME/CFS have problems converting the body’s fuel, primarily fats and sugars, into energy.
  • Low blood pressure.
  • Immune system changes (how your body responds to stress or an infection). Immune system changes include natural killer cell dysfunction and/or T-cell dysfunction, elevated cytokines, and autoantibodies 40
    • It has been observed that alterations in the levels of CD 21+ CD19+ and activated CD5+ cells in patients with chronic fatigue syndrome 41.
    • There is also a reported decrease in transitional B cells and plasmablasts and an increase in the population of CD24+ B cells in these patients 42, 43.
    • Studies have shown a lower number of CD3-CD57 white cells lymphocytes, which are a type of NK cell, whereas the levels of the cytotoxic T cells were not changed 44, 45, 46. CFS is associated with increased production of the CD20+ CD5+ B cell phenotypes correlating with increased autoantibody production and overexpression of CD21 markers acting as receptors for some viruses 42, 43.
    • Researchers have also found elevations in the levels of immunoglobulin G (IgG) in several studies, again pointing to alteration in the immune functioning of these patients 47, 48.
    • Several studies have also described the presence of autoantibodies against nuclear and membrane structures as well as against neurotransmitter receptors 49, 50, 51, 52.
  • Weak immune system. It is also theorized that there are low circulating cortisol levels in patients with chronic fatigue syndrome secondary to dysfunction in the hypothalamic-pituitary axis (HPA). Cortisol is the principal hormone of the hypothalamic-pituitary axis (HPA) and leads to the cortisol awakening response. This response is deficient in patients with CFS, leading to the post-exertional malaise 53.
  • Genetics. Chronic fatigue syndrome appears to run in some families, so some people may be born with a higher likelihood of developing ME/CFS 54. Studies from the twin registry also have shown increased familial and genetic predisposition to developing ME/CFS 55, 56. A study observed variability in the expression of specific genes in patients with CFS, particularly after exercise, which affects the metabolism and immune responses 57. In another study, an association was reported between CFS and specific genetic mutations and viral infections 58.
    • Studies have shown an interaction between changes in the genes secondary to changes in the environment, leading to epigenetic modification. DNA methylation appears to be the most studied of these epigenetic modifications that can alter the expression of the gene concerning the environmental stimuli and lead to the development of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disease process 59.

Some studies report chronic fatigue syndrome patients to have significantly increased oxidative stress, which plays a vital role in the pathogenesis of the disease. There is an increase in oxidative stress biomarkers like oxidized LDL and certain prostaglandins and, at the same time, a decrease in the amounts of the antioxidants like glutathione 60, 61. The oxidative damage transforms the fatty acids and proteins into immunogenic targets 62. The free radicals also damage the electron transport chain causing impaired energy production and mitochondria 63. The mechanism underlying mitochondrial dysregulation is not entirely known 64, 65, 66.

There is also an alteration in the immunoglobulin number and distribution in patients with chronic fatigue syndrome. The total immunoglobulin G (IgG) level, particularly subclasses IgG1 and IgG3, is substantially lower. In contrast, there is an increase in IgA and IgM serum levels against the lipopolysaccharides of the normal gram-negative bacteria due to alterations in gut permeability 67, 68. These can also serve as corroborative evidence for CFS.

Studies have also detected autoantibodies against certain neurotransmitters and neurons, leading to alterations in neurotransmitter response, sleep patterns, and neurocognition 51, 69. Researchers have found antinuclear antibodies (ANA), anti-dsDNA antibodies, and antibodies against neuronal and endothelial cells in these patients 70. Moreover, antibodies against the muscarinic M1 acetylcholine beta-adrenergic receptors have been detected in these patients 51, 30. Disturbance in these receptors could explain symptoms of autonomic dysregulation in CFS patients 71.

The presence of proinflammatory changes causes speculation about the involvement of neuroinflammation in the pathogenesis and clinical presentation of myalgic encephalomyelitis or chronic fatigue syndrome disease process 72. Multiple studies show that the constant proinflammatory state that occurs in CFS causes activation of glial cells, specifically microglia and astrocytes. These activated glial cells produce the expression of a translator protein, which appears to activate inflammation in the central nervous system (brain and spinal cord) 73. The increase in glial activation leads to an increase in neuronal excitation and neuronal inflammation, which is supposed to be the leading cause of chronic pain symptoms in myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) patients 74. Studies are also evaluating the role of “glial toxins” produced by multiple viruses and bacteria, leading to direct damage to these glial cells 75.

Central fatigue, a key symptom in patients with chronic fatigue syndrome, is hypothesized to be due to excess levels of serotonin and its metabolites in the central nervous system of these patients 76. The excess serotonin leads to inhibition of the action potential generation and thus reduced motor activity and appears to be a leading contributor to the fatigue symptoms of these patients 77, 78.

Neuronal sensitization due to the chemical and structural changes at the central nervous system level has been theorized to cause an exaggerated response to painful stimuli in patients with CFS 74. This exaggerated response leads to the formation of sensitized neurons that keep the stimulus going due to the process of “kindling” 4.

Risk factors for developing chronic fatigue syndrome

Factors that may increase your risk of chronic fatigue syndrome include:

  • Age. Chronic fatigue syndrome can occur at any age, but it most commonly affects young to middle-aged adults.
  • Sex. Women are diagnosed with myalgic encephalomyelitis or chronic fatigue syndrome much more often than men, but it may be that women are simply more likely to report their symptoms to a doctor.
  • Other medical problems. People who have a history of other complex medical problems, such as fibromyalgia or postural orthostatic tachycardia syndrome, may be more likely to develop ME/CFS.

Chronic fatigue syndrome symptoms

Chronic fatigue syndrome symptoms vary widely from person to person and its onset can be unpredictable. Your ME/CFS symptoms may come and go. Symptoms of myalgic encephalomyelitis or chronic fatigue syndrome are often triggered by physical activity or emotional stress. This can make it difficult for people to maintain a regular work schedule or to even take care of themselves at home. Many people may be too weak to get out of bed at different points during their illness. They may change over time; sometimes they might get better, and other times they may get worse. Some people may need to use a wheelchair.

The primary, or core, symptoms of chronic fatigue syndrome (CFS) are 6, 59, 79, 80, 81, 82, 83, 84:

  • Not being able to do activities that you used to do before the illness, along with severe fatigue. The fatigue must last six months or longer, and it is not improved by rest or sleep.
  • Post-exertional malaise, which means that your symptoms get worse after any physical or mental activity. Post-exertional malaise usually begins within 12 to 24 hours after your activity, and it can last for days or weeks. People who have post-exertional malaise often struggle to find a good balance between activity and rest. The goal is to remain active without overdoing it. This is also called pacing or activity management. The goal is to learn to balance rest and activity to avoid flare-ups. These can be caused by exertion that patients cannot tolerate.
  • Difficulty sleeping (falling or staying asleep).
  • Problems with thinking, attention, concentration and memory.
  • Worsening of symptoms while standing or sitting upright, this is called orthostatic intolerance. It can cause you to feel lightheaded, dizzy, weak, or faint while standing or sitting up.

People who have chronic fatigue syndrome may also experience the following symptoms 59, 79, 80, 81, 82, 83, 85, 86, 87, 88, 89:

  • Fatigue.
  • Headaches.
  • Sore throat.
  • Tender or painful areas in your neck or armpits due to swollen lymph nodes or lymph glands.
  • Muscle soreness.
  • Pain, including muscle pain, joint pain, and headaches.
  • Joint pain that moves from joint to joint without swelling or redness.
  • Loss of memory or concentration.
  • Trouble sleeping.
  • Digestive issues, like irritable bowel syndrome (IBS) with painful bloating, gas, constipation and diarrhea.
  • Chills and night sweats.
  • Allergies and sensitivities to foods, odors, chemicals, light, or noise.
  • Extreme tiredness after exercising that lasts more than 24 hours.

Other symptoms of CFS include:

  • Vision problems.
  • Chills.
  • Night sweats.
  • Swollen lymph nodes.
  • Mood swings, irritability and anxiety.
  • Tingling or numbness in your feet, hands or face.
  • Dizziness, weakness and fainting.

For many people, the symptoms of CFS resemble other conditions, like the flu. Symptoms may come and go over time and increase or decrease in severity. Chronic fatigue syndrome symptoms get worse following physical exercise or strenuous mental exertion (post-exertional malaise). Many of the symptoms of CFS make daily life difficult. For some people, the fatigue associated with chronic fatigue syndrome makes activities of daily living very difficult or even impossible. Research shows that only half of all people diagnosed with CFS work full-time or part-time jobs.

CFS can also cause depression. If you experience depression, see with your healthcare provider. Effective treatments are available.

Chronic fatigue syndrome diagnosis

Chronic fatigue syndrome (CFS) can be difficult to diagnose because there is no specific test for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other illnesses can cause similar symptoms. Your doctor will diagnose chronic fatigue syndrome after reviewing your symptoms, medical history, your family’s medical history and doing a physical exam and mental health evaluation. Asking about your current illness, including your symptoms. Some questions your doctor may ask could include how often you have symptoms, how bad they are, how long they have lasted, and how they affect your life.

The typical approach to a patient with chronic fatigue should begin with a history and physical examination, identifying the underlying symptoms and ruling out any serious illnesses. Your doctor should use a validated clinical questionnaire like the DePaul symptom questionnaire or the Center for Disease Control Symptom Inventory (see below) 90.

  • What are you able to do now?
  • How does it compare to what you were able to do before you became sick?
  • How long have you felt this way?
  • How do you feel after sleeping or resting?
  • What makes you feel worse? What helps you feel better?
  • What happens when you try to push to do activities that are now hard for you?
  • Are you able to think as clearly as you did before becoming ill?
  • What symptoms keep you from doing what you need or want to do?
  • What symptoms do you have when you stand or sit upright?
  • How much activity, either physical or mental, does it take for you to feel ill?
  • How long does it take for you to feel better after such exertion?
  • What activities do you now avoid because of what happens after?
  • Do you ever feel dizzy or lightheaded?
  • Have you been falling more often than before?
  • Do you feel worse when standing for more than 5 minutes
  • Do you feel worse in warm environments?

Consider asking patients to document their activities and symptoms for a couple of weeks in a diary.

For children, the questions may need to be adapted and parents may be an important resource. Depending on the age of the child, the questions might be asked of the patient, parent/guardian, or both (together or independently).

Your doctor has to rule out other diseases before making a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, with tests like blood or urine tests help your doctor look for possible causes and rule out conditions with similar symptoms.

The diagnostic criteria for CFS, or the things that your doctor will look for during an exam, include:

  • Severe fatigue that lasts at least six months. Fatigue doesn’t improve with rest or sleep.
  • Difficulty getting restful sleep.
  • Fatigue that gets worse after mental or physical activity.
  • Orthostatic intolerance (inability to sit up without feeling symptoms) and/or problems with cognitive function (thinking and memory).

Your doctor may also ask you to see a specialist to check for other conditions which can cause similar symptoms. Other healthcare professionals with training and experience in assessing, diagnosing, treating and managing ME/CFS. These specialists are medically trained clinicians from a variety of specialisms including rheumatology, rehabilitation medicine, endocrinology, infectious diseases, neurology, immunology, and paediatrics.

Patients with unexplained impaired function with fatigue for 6 months or longer who do not fully meet the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) case definition can be managed like patients with ME/CFS and monitored for change.

There are no diagnostic tests or single biomarkers of CFS. Tests to rule out other causes are undertaken in the context of the particular patient. The standard laboratory tests include urinalysis, complete blood count with differential, blood chemistries, thyroid function tests, muscle enzymes like creatine kinases, and C- reactive protein 91. The national institute for clinical excellence (NICE) also conducts tests for gluten sensitivity and recommends using immunoglobulin A endomysial antibodies, urine drug screening, and rheumatological antibodies as indicated 92, 93. It also recommends against using viral titers unless necessary after the patient’s clinical examination 92, 93.

Chronic fatigue syndrome diagnostic criteria

Guidelines proposed by the United States Institute of Medicine define the fatigue associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as being 94:

  • So severe that it interferes with the ability to engage in pre-illness activities.
  • Of new or definite onset.
  • Not substantially alleviated by rest.
  • Worsened by physical, mental or emotional exertion.

To meet the 2015 Institute of Medicine’s diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a person would also need to experience the presence of the following three symptoms for more than 6 months as well as the intensity of the symptoms should be moderate or severe for at least 50% of the time 94, 95:

The 3 main symptoms include:

  1. Fatigue – A noticeable decrease or impairment in a patient’s ability to engage in activities they would have enjoyed before the onset of the illness. This impairment continues for more than six months and is associated with new-onset severe fatigue unrelated to exertion and not relieved by rest.
  2. Post-exertional malaise – Patients experience worsening symptoms and function after exposure to physical or cognitive stressors, which they previously well tolerated.
  3. Unrefreshing sleep – patients feel tired after a night’s sleep.

Criterion fulfillment for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis requires the 3 above-stated symptoms plus one of the additional below-mentioned symptoms 94, 95:

  • Cognitive impairment – Problems with the thought or executive function worsened by exertion, effort, stress, or time pressure.
  • Orthostatic intolerance – Dizziness that worsens with moving from lying down or sitting to standing. Although not necessarily abolished, symptoms are improved by lying back down or elevating the feet.

Chronic fatigue syndrome differential diagnosis

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms can mimic many other health problems, including:

  • Sleep disorders. Fatigue can be caused by sleep disorders. Undiagnosed obstructive sleep apnea (OSA) can present with fatigue and unrefreshing sleep, two of the main diagnostic criteria for chronic fatigue syndrome. A sleep study can determine if your rest is being disturbed by disorders such as obstructive sleep apnea, restless legs syndrome or insomnia.
  • Mental health issues. Fatigue is also a symptom of a variety of mental health problems, such as depression and anxiety. Roughly 20% of the patients presenting to primary care clinics have an underlying undiagnosed depressive illness 96. There could be a range of undiagnosed or underdiagnosed disorders like major depressive disorder, bipolar disorder, eating disorder, schizophrenia, somatoform disorders, and substance abuse. It is of the utmost importance to remember that in the elderly, symptoms of fatigue, unrefreshing sleep, and cognitive decline can be very much part of the symptom complex of late-onset depression 97. A counselor can help determine if one of these problems is causing your fatigue.
  • Rheumatological disorders. Fibromyalgia, polymyalgia rheumatica, polymyositis, and autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjogren syndrome can have similar symptoms to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) 98, 99, 100. It requires proper history, clinical examination, and laboratory testing for autoantibodies before arriving at the correct diagnosis.
  • Endocrine disorders. There could be adrenal abnormalities (Addison disease, adrenal insufficiency, Cushing disease), thyroid abnormalities (both underactive thyroid (hypothyroidism) and overactive thyroid (hyperthyroidism)), and diabetes, which can mimic symptoms of chronic fatigue syndrome.
  • Hematological disorders and cancers. Fatigue is a common symptom in several medical conditions, such as anemia, and undiagnosed cancers 101. Anemia from any cause can present with excessive tiredness and fatigue 102, 103, 104, 105. Lab tests can check your blood to look for possible causes and rule out other medical problems with similar symptoms.
  • Infectious diseases. Infectious diseases like the human immunodeficiency virus (HIV), tuberculosis (TB) and chronic hepatitis can have ongoing fatigue as their initial presentation.
  • Gastrointestinal disorders. Inflammatory bowel disease (IBD) can present with chronic fatigue symptoms 106. Celiac disease can present with fatigue and sometimes even without gastrointestinal symptoms.
  • Neurological disorders. Fatigue is the main presenting feature of multiple sclerosis 107. Dementia, which has cognitive impairment as its major presentation, can cause a diagnostic dilemma, as can pseudodementia.
  • Respiratory disorders. Chronic respiratory conditions like chronic obstructive pulmonary disease (COPD) and sarcoidosis can present with chronic fatigue 108.

Chronic fatigue syndrome treatment

At the present time there is no cure for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) treatment focuses on managing your symptoms. Your most disruptive or disabling symptoms should be addressed first.

The goal of any chronic fatigue syndrome (CFS) treatment is to reduce your symptoms so you can regain function in your life. Some people aren’t able to regain the level of health and function they had before their diagnosis.

Treatment for chronic fatigue syndrome (CFS) may include:

  • Changes to your sleep routine.
  • Medications.
  • Activity management.

There are also various chronic fatigue syndrome resources and strategies that might be helpful to you, such as:

  • Getting counseling to help you cope with the illness and its impact on your life.
  • Eating a healthy diet.
  • Nutritional supplements, if your provider suggests them.
  • Complementary therapies such as meditation, gentle massage, relaxation therapy, deep breathing, muscle relaxation, massage, yoga, and tai chi may be of benefit.

Make sure to talk to your doctor before you try any new treatments. Some treatments that are promoted as cures for myalgic encephalomyelitis or chronic fatigue syndrome are unproven, often costly, and could be dangerous.

You, your family, and your doctor should work together to decide on a management plan. You should figure out which symptom causes you the most problems and try to treat that first. For example, if sleep problems affect you the most, you might first try using good sleep habits. If those do not help, you may need to take medicines or see a sleep specialist.

Strategies such as learning new ways to manage your daily activity can also be helpful. You need to make sure that you do not “push and crash”. This can happen when you feel better, do too much, and then get worse again.

When you have myalgic encephalomyelitis or chronic fatigue syndrome, it can be hard to help develop a treatment plan. It can also be difficult to try to take care of yourself. So it’s important that you have support from family members and friends.

Sleep routine changes

Lack of sleep can make your other symptoms more difficult to deal with. Your doctor might suggest avoiding caffeine or changing your bedtime routine. Sleep apnea can be treated by using a machine that delivers air pressure through a mask while you sleep.

Your doctor may also recommend the following at-home sleeping habits to improve your rest (sleep hygiene) before prescribing medications or starting other forms of treatment. These may include:

  • Developing a regular bedtime routine, like going to bed and waking up at the same time each day.
  • Not napping for more than 30 minutes total during the day.
  • Using your bed and bedroom only for sleeping and sexual intercourse. Remove all electronics.
  • Avoid eating large meals before you go to bed. Also, avoid alcohol and caffeine before bed.

Medications for chronic fatigue syndrome

Your doctor may recommend medications to treat your CFS symptoms:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) for relieving pain and associated inflammation 109, 110. If NSAID medicines such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve) don’t help you with your pain, prescription drugs sometimes used to treat fibromyalgia might be options for you. These include pregabalin (Lyrica), duloxetine (Cymbalta), amitriptyline or gabapentin (Neurontin).
  • Tricyclic antidepressants for sleep, pain and fatigue 109. The tricyclic antidepressants doses used for chronic fatigue syndrome are typically lower than the doses used in the treatment of depression 111.
  • Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for depression and pain relief. Many selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, sertraline, and paroxetine have been used to treat depression and anxiety, which either accompany chronic fatigue syndrome disease process or occur as a consequence. Serotonin-norepinephrine reuptake inhibitors (SNRIs) have the added benefit of providing neuropathic pain relief besides the antidepressant effect. However, neither SSRIs nor SSNRIs directly affect the underlying pathophysiology of CFS disease process 112.
  • Antivirals for a virus infection. Several antiviral medications have been tried in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, but most of these studies have been inconclusive 113, 114. Randomized controlled trials (RCTs) comparing the effect of nucleotide analog inhibitors like acyclovir, valacyclovir, and ganciclovir, versus placebo, have shown no difference in symptom control 115. Studies using interferons versus placebo in chronic fatigue syndrome also did not show evidence of clear benefit 116.
  • Intravenous immunoglobulin (IVIG) to improve how your immune system functions. A systemic review conducted by White et al. in 2011 117)) evaluated five randomized controlled trials on the use of immunoglobulins in patients with chronic fatigue syndrome. It revealed positive results in four of them 112. Unfortunately, other studies did not report any benefit and concluded the potential dangers of the immunoglobulins.
  • Corticosteroids for fatigue. Multiple randomized controlled trials and systemic reviews performed with corticosteroids in 2005 showed varying responses. One systemic review conducted in 2015 showed a weak benefit from low-dose hydrocortisone, but the effect was only short-lived and was associated with adverse effects 118.
  • Medications to regulate blood pressure or heart rhythms may be helpful for people with orthostatic intolerance.
  • Complementary and alternative medicines. Systemic reviews of the studies using essential fatty acids, magnesium, acetyl-l-carnitine, vitamin B12, and antioxidants have shown only partial response and require further studies 119.

Clinical trials are ongoing to learn more about new medications that can treat your symptoms.

  • Rintatolimod (Ampligen) is a newly approved immunomodulator and an antiviral drug for treating chronic fatigue syndrome in Canada and Europe 120. A randomized controlled trial published in the journal of the American medical association (JAMA) in 2001 showed Rintatolimod mixed results in CFS patients 121. However, the U.S. FDA rejected Rintatolimod (Ampligen) to be marketed in the U.S. for CFS treatment, citing insufficient safety and efficacy data.
  • Rituximab is an anti-CD20 monoclonal antibody causing the depletion of B cells. An initial small double-blind, placebo-controlled trial of 30 patients with CFS receiving rituximab showed some benefit, leading the researchers to hypothesize that B cells might have a significant role in the pathogenesis of some patients with chronic fatigue syndrome 122. However, a more extensive study showed no fatigue difference between patients who received rituximab versus those who did not. Also, patients receiving rituximab showed more adverse effects, including neutropenia and infections 123.
  • Fecal Microbiota Transplantation. Alteration in gastrointestinal (GI) microbiota in CFS patients has been hypothesized as one of the causes 124, 125. Trials of fecal microbiota transplantation are an exciting, relatively safe, and rapidly growing treatment modality that is currently undergoing experimentation to manage multiple medical conditions, including CFS 126, 127. The process involves the transfer of feces from a healthy donor into a patient’s gut 128. In recent years, numerous studies have shown significant symptom relief in these patients after the fecal microbiota transfer provides promising therapeutic insights 129, 130.

Even though there has been some success with the fecal microbiota, it is still too early to conclude anything. However, it opens doors for future research in this direction.

Cognitive-behavioral therapy (CBT) and graded exercise therapy (GET)

A randomized control trial conducted in 2011 in the United Kingdom compared the effectiveness and safety of cognitive-behavioral therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT), and specialist medical care in the management of chronic fatigue syndrome. Overcoming fatigue and improvement of physical function were taken as measures of effectiveness, while safety assessment comprised recording all adverse effects. The results showed that cognitive-behavioral therapy (CBT) and graded exercise therapy (GET) improved outcomes when used together, whereas adaptive pacing therapy (APT) was not a helpful addition 112.

During the cognitive-behavioral therapy (CBT) sessions, the therapist emphasizes the role of the thought process and its impact on the patient’s actions and feelings and recognizes behaviors that cause them to feel more tired and minimize them. Multiple trials and Cochrane reviews have shown the positive benefits of CBT on improving fatigue, mood, and post-exertional malaise in both adolescent and adult patients 131, 132, 133, 134. Studies have also shown lower school absences when CBT is provided to the adolescent population 135.

Graded exercise therapy (GET) involves a supervised, gradual increase in the duration and intensity of physical activity. After the adaptive pacing therapy (APT), cognitive behaviour therapy (CBT), graded exercise therapy (GET), and specialist medical care for chronic fatigue syndrome (PACE) trial, graded exercise therapy (GET) got much publicity, which showed effectiveness for fatigue and functional impairment with the graded exercise therapy (GET) 112. The PACE trial encouraged the participants to gradually increase the timing of their physical activity to a final goal of 30 minutes, spread over 52 weeks to a final goal of 30 minutes of light exercise five days per week while trying to avoid overexertion 112. Other studies have also supported graded exercise therapy (GET) efficacy 136, 137, 138. However, CBT and GET can be used as add-on management options, but they are not curative.

Activity management for post-exertional malaise

Physical activity and mental exertion can make symptoms of fatigue worse, this is called post-exertional malaise. It usually begins within 12 to 24 hours after your activity, and it can last for days or weeks. Your doctor may recommend an activity management practice called pacing to treat post-exertional malaise symptom. Pacing balances your rest and activity levels. The goal of pacing is to reduce post-exertional malaise, rather than getting back to the same activity level you had when you were healthy. As you improve, you may be able to safely engage in more activity without triggering post-exertional malaise.

When you practice pacing, you learn what your limitations are. Limitations are like a fence or boundary. You want to stay within a certain area where it’s safe for your body. Overexertion happens when you step out of the boundary; your body has trouble adjusting to the environment beyond its limits. This can make your symptoms worse.

Your doctor will work with you to set your physical and mental limits so you stay within a range that your body can handle. It might help to keep a diary or journal of your activity and symptoms to understand what you do and how it makes you feel. Once you determine your limitations, you’ll need to plan your activities around them to make sure you feel well enough to function.

Exercising or strenuous activity, like aerobic exercises, can make your symptoms worse. Your doctor can help you manage the condition and find physical activities that are safe for you.

Living with chronic fatigue syndrome

There are strategies for dealing with the daily challenges of CFS. These may work for you, especially in combination with medications prescribed by your doctor.

  • Keep a daily diary to identify times when you have the most energy. Plan your activities for these times.
  • Keep up some level of activity and exercise, within your abilities. Your doctor can help you plan an exercise program to maintain your strength at whatever level is possible. Exercise can help your body and mind.
  • Give yourself permission to recognize and express your feelings, such as sadness, anger, and frustration.
  • Ask for support from family and friends. Look for support groups or counseling in your community. However, support groups aren’t for everyone, and you may find that a support group adds to your stress rather than relieves it. Your doctor is another important source of help. Emotional support is important in coping with a chronic health problem. Experiment and use your own judgment to determine what’s best for you.
  • If your memory and concentration are affected by chronic fatigue, keep lists and make notes to remind yourself of important things. Also, give yourself more time for activities that take concentration. Medicine may also help you sleep better, which might improve your memory and concentration.

Chronic fatigue syndrome coping and support

The experience of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) varies from person to person. Emotional support and counseling may help you and your loved ones deal with the uncertainties and restrictions of ME/CFS.

Talking with a counselor can help build coping skills to deal with chronic illness, address limitations at work or school, and improve family dynamics. It also can be helpful if you are dealing with symptoms of depression.

You may find it helpful to join a support group and meet other people with your condition. Support groups aren’t for everyone, and you may find that a support group adds to your stress rather than relieves it. Experiment and use your own judgment to determine what’s best for you.

Chronic fatigue syndrome prognosis

At the present time, because scientists don’t know what causes chronic fatigue syndrome, there’s no cure for chronic fatigue syndrome and the symptoms can persist for years. You may be able to manage symptoms with sleep and activity changes and medications. With treatment, most chronic fatigue syndrome symptoms improve. The goal of treatment is to make your symptoms as manageable as possible to increase your quality of life. But some people don’t return to the same health or functional state as they were before their symptoms appeared.

Chronic fatigue syndrome affects everyone differently. Its clinical course fluctuates between remissions and relapses. According to one prospective study, around 50% of patients with CFS may return to part-time or full-time work 139. Factors associated with poor prognosis include longer duration of illness, comorbid depression, severe fatigue, and anxiety 140.

Favorable outcomes are associated with less severity of fatigue at baseline, a better sense of control over symptoms, and the absence of any attribution of chronic fatigue syndrome to a physical cause 141. Although a considerable burden of sickness and reduction in quality of life is linked with CFS, there is evidence of increased mortality 4.

You’ll have to be careful not to over-extend your activity. Pacing yourself during both mental and physical exertion can help your body recover. Taking breaks and alternating between physical and mental tasks can be helpful.

Your doctor may recommend that you join a support group for people living with CFS. These groups can help you cope with the condition by putting you in touch with others who know exactly what you’re going through.

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