Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by profound fatigue that is not improved by bed rest and may be worsened by physical, emotional or mental stress. Patients report various nonspecific symptoms, including weakness, chemical sensitivities, allergies, poor immune function, muscle pain, impaired memory and/or mental concentration, insomnia, and post-exertional fatigue lasting more than 24 hours. In some cases, CFS can persist for years. The cause, or causes, of CFS have not been identified and no specific diagnostic tests are available. Moreover, since many illnesses have incapacitating fatigue as a symptom, care must be taken to exclude other known and often treatable conditions before a diagnosis of CFS is made.
Diagnostic Criteria for Chronic Fatigue Syndrome
1. new onset of fatigue causing 50% reduction in activity for at least six months
2. exclusion of other illnesses that can cause fatigue
1. presence of eight of 11 symptoms, or
2. presence of six of 11 symptoms and two of three signs:
1. mild fever
2. recurrent sore throat
3. painful lymph nodes
4. muscle weakness
5. muscle pain
6. migratory joint pain
7. prolonged fatigue after exercise
8. recurrent headaches
9. neurological or psychological complaints, such as: • depression • excessive irritability • forgetfulness • sensitivity to bright light • confusion • inability to concentrate
10. sleep disturbances
11. sudden onset of symptom complex
Signs: 1. low-grade fever 2. non-exudative pharyngitis (sore throat) 3. tender lymph nodes
Similar Medical Conditions
A number of illnesses have been described that have a similar spectrum of symptoms to CFS. These include fibromyalgia syndrome, myalgic encephalomyelitis, neurasthenia, multiple chemical sensitivities, and chronic mononucleosis. Although these illnesses may present with a primary symptom other than fatigue, chronic fatigue is commonly associated with all of them.
Other Conditions That May Cause Similar Symptoms
In addition, there are a large number of clinically defined, frequently treatable illnesses that can result in fatigue. Diagnosis of any of these conditions would exclude a definition of CFS unless the condition has been treated sufficiently and no longer explains the fatigue and other symptoms. These include hypothyroidism, sleep apnea and narcolepsy, major depressive disorders, chronic mononucleosis, bipolar affective disorders, schizophrenia, eating disorders, cancer, autoimmune disease, hormonal disorders*, subacute infections, obesity, alcohol or substance abuse, and reactions to prescribed medications.
Other Commonly Observed Symptoms in CFS
In addition to the eight primary defining symptoms of CFS, a number of other symptoms have been reported by some CFS patients. The frequencies of occurrence of these symptoms vary from 20% to 50% among CFS patients. They include abdominal pain, alcohol intolerance, bloating, chest pain, chronic cough, diarrhea, dizziness, dry eyes or mouth, earaches, irregular heartbeat, jaw pain, morning stiffness, nausea, night sweats, psychological problems (depression, irritability, anxiety, panic attacks), shortness of breath, skin sensations, tingling sensations, and weight loss.
Possible Causes of CFS
Due to weakened immunity, individuals with chronic fatigue have terrible problems with energy as well as reoccurring bouts with the flu, colds, sinusitis, and other immune problems. As with so many complex chronic illnesses, CFS may be aggravated by a wide variety of environmental and physiological challenges. Food allergies, environmental sensitivities (odors), heavy metal toxicity (mercury, aluminum, etc.), yeast overgrowth, parasites, and vitamin/mineral deficiencies can all contribute to CFS.
The cause, or causes, of CFS remain unknown despite a vigorous search. While a single cause for CFS may yet be identified, another possibility is that CFS represents a common endpoint of disease resulting from multiple precipitating causes. As such, it should not be assumed that any of the possible causes listed below has been formally excluded, or that these largely unrelated possible causes are mutually exclusive. Conditions that have been proposed to trigger the development of CFS include virus infection or other transient traumatic conditions, stress, and toxins.
Unfortunately, some physicians believe that CFS is a component of a psychological disorder or a symptom of other problems, similar to anemia and high blood pressure. Indeed, no primary cause has been found that explains all cases of CFS. A number of experts believe that CFS is caused by a combination of conditions that overwhelm the person’s stress coping abilities. These conditions or triggers may include the following:
• Genetic factors.
• Brain abnormalities or inability of the self-regulating mechanisms.
• A hyper-reactive immune system.
• Viral, bacterial, fungal, mycoplasma or other infectious agents.
The majority of patients report some preceding moderate to serious physical (eg, a chronic viral infection) or emotional event (eg, episode of depression). Some experts theorize that such events alone or in combination coupled in people with certain neurological and genetic abnormalities may overwhelm the person’s ability regulate their own homeostatic self-regulating systems.
Dysfunction of the Hypothalamus-Pituitary-Adrenal Axis
Researchers investigating CFS are looking at the abnormalities in the brain system known as the hypothalamus-pituitary-adrenal axis. This system produces or regulates hormones and brain chemicals that control important functions, including sleep, response to stress, and depression. This is our self-regulating, homeostatic system. Stress Hormone
A number of studies on CFS patients have observed deficiencies in cortisol levels, a stress hormone produced in the hypothalamus. Deficiencies may be the reason why CFS patients have an impaired and weaker response to psychological or physical stresses (such as infection or exercise).
Abnormalities in Neurotransmitters
Other research has reported that some patients with CFS have abnormally high levels of serotonin, a neurotransmitter (chemical messenger in the brain). Such elevated levels in the brain are associated with fatigue. Yet another study reported that deficiencies in dopamine and norepinephrine, other important neurotransmitters, may play a role in CFS.
Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases.
There are three basic theories for infection-related causes of CFS
Some researchers suggest that chronic fatigue syndrome might be the result of a virus or bacteria that infects the body, causes immune abnormalities, and is then eliminated. It leaves behind a damaged immune system, however, that continues to cause flu-like symptoms even in the absence of the virus. The flu-like symptoms are most pronounced when the person is under stress. The evidence for CFS having a viral cause is not based on hard evidence but on various observations that suggest an association, such as the following:
• In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition.
• In the US, outbreaks of CFS occurring within the same household, workplace, and community have been reported (but most have not been confirmed by the Centers for Disease Control).
• A large British study of people with both diagnosed CFS and idiopathic chronic fatigue also found no evidence of infection as a direct cause of either condition, but found that previous infections may play some role.
• Although no specific virus has been identified as a single cause, CFS patients typically have elevated levels of antibodies to many viruses that cause fatigue and other CFS symptoms, including Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLV), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus.
• In one study, some patients, particularly those with severe CFS symptoms, had higher-than-normal numbers of infection-fighting white blood cells known as CD8 killer T cells, which launch attacks on invading viruses and other disease-causing microorganisms. These same people had lower-than-normal levels of another white blood cell known as the suppressor T cell, which helps to shut down the immune response once the invading organisms have been killed. In such cases, the immune system becomes persistently overactive and produces fatigue, muscle aches, and other symptoms of CFS.
Several investigators have reported lower numbers of natural killer cells or decreased natural killer cell activity among CFS patients compared with healthy controls, but others have found no differences between patients and controls.
T-cell activation markers have also been reported to have differential expression in groups of CFS patients compared with controls, but again, not all investigators have consistently observed these differences. One intriguing hypothesis is that various triggering events, such as stress or a viral infection, may lead to the chronic expression of cytokines and then to CFS.
Administration of some cytokines in therapeutic doses is known to cause fatigue, but no characteristic pattern of chronic cytokine secretion has ever been identified in CFS patients. In addition, some investigators have noted clinical improvement in patients with continued high levels of circulating cytokines; if a causal relationship exists between cytokines and CFS, it is likely to be complex. Finally, several studies have shown that CFS patients are more likely to have a history of allergies than are healthy controls. Allergy could be one predisposing factor for CFS, but it cannot be the only one, since not all CFS patients have it.
Some of the Immune Disorders Associated with CFS are Listed Below:
• Elevated levels of antibodies to various viruses.
• Altered helper/suppressor T-cell ratio.
• Decreased Natural Killer (NK) cells or activity.
• Decreased levels of circulating immune complexes.
• Low or elevated antibody levels.
• Increased cytokine levels.
• Increased or decreased interferon levels.
• Fibromyalgia and multiple chemical sensitivities.
The History of CFS
Epstein - Barr virus (EBV), Origin
There have been several studies that have focused on identifying an infectious agent as the cause of CFS. The Epstein-Barr virus (EBV) has received a lot of attention over the last two decades.
In 1985, reports were published in the Annals of Internal Medicine about a mysterious severe viral epidemic the gripped the Lake Tahoe region in California. Initially, CFS was presumed to be caused by the Epstein - Barr virus because research at the National Institutes of Health confirmed the presence of elevated levels of antibodies against EBV in afflicted people. As times passed, EBV was deemed to be one of many viruses associated with CFS. But is CFS caused by these viruses? Or, do the viruses only show themselves once CFS manifests itself? EBV is a member of the Herpes group of viruses, which include Herpes Simplex Types 1 and 2, Varicella zoster virus, Cytomegalovirus, and Psuedorabies virus. A common aspect of these viruses is their ability to establish lifelong latent infection after the initial infection. This latent infection is kept in check by a healthy immune system.
We know that EBV causes the debilitating disease of teenhood, “Infectious Mononucleosis”, or in lay parlance ‘Mono’ (sometimes called ‘the kissing disease’). But not everyone who carries this virus develops "Mono." In fact, over 90% of Americans have been exposed to EBV by age 20. Some of these individuals develop infectious mononucleosis; others simply experience flu-like symptoms for a few days, but most show no symptoms at all.
CFS and Immune Dysfunction
EBV and the Herpes group of viruses can produce chronic lifelong infections. Most individuals have been exposed to one of these viruses and build immunity to them. Persons with a compromised immune system are susceptible to latent infections including EBV. The infection itself can compromise the immune system. Elevated EBV antibodies to the Herpes-group of viruses (Cytomegalovirus, Herpes 6, etc.,) measles, and other viruses have been observed in patients suspected of having CFS and who also display elevated EBV antibody levels. There is little argument that a disturbed immune system plays a central role in CFS, A variety of immune system abnormalities have been observed in EBV cases. The most consistent abnormality is a decreased number of or activity of natural killer (NK) cells. Natural killer cells are used to destroy cells that are infected with cancerous or viral toxins.
As with so many complex chronic illnesses, CFS may be caused and aggravated by a wide variety of environmental and physiological challenges. Food allergies, environmental sensitivities, heavy metal toxicity, yeast overgrowth, intestinal dysbiosis, parasites, and vitamin/mineral deficiencies can all contribute to CFS. These disorders must be found and eliminated with a systematic protocol based on correcting causes and not merely covering up symptoms.
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