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CHRONIC FATIGUE SYNDROME

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Please note that most treatment modalities listed below are based on conventional medicine. PreventDisease.com does advocate the use of any pharmaceutical drug treatments. Long-term drug therapy is detrimental to human health. All drug information is for your reference only and readers are strongly encouraged to research healthier alternatives to any drug therapies listed.


WHAT IS CHRONIC FATIGUE SYNDROME AND ITS SYMPTOMS?


Chronic fatigue syndrome (CFS), also sometimes called immune dysfunction syndrome or myalgic encephalomyelitis (in Europe), is not a new disorder. In the 19th century the term neurasthenia, or nervous exhaustion, was applied to symptoms resembling CFS. In the 1930s through the 1950s outbreaks of disease marked by prolonged fatigue were reported in the United States and many other countries. Beginning in the early to mid-1980s interest in chronic fatigue syndrome was revived by reports in America and other countries of various outbreaks of long-term debilitating fatigue.

Fatigue that lasts for more than six months, impairs normal activities, and has no identifiable medical or psychological problems to account for it is referred to as unexplained chronic fatigue. This condition, however, is not considered to be chronic fatigue syndrome unless it meets certain criteria [ see Box ]. If it does not meet these criteria, then the condition is referred to as idiopathic chronic fatigue . (Idiopathic simply means that the cause is not known.) It should be noted that six million patient visits are made each year because of fatigue, although only a very small percentage of these can be attributed to actual chronic fatigue syndrome.

Criteria for Chronic Fatigue Syndrome

The Centers for Disease Control define CFS as a distinct disorder with specific symptoms and physical signs after eliminating other identifiable causes of these symptoms and signs.

1. Four or more of the following symptoms must have been present for longer than six months:
  • Short-term memory loss or a severe inability to concentrate that affects work, school, or other normal activities.

  • Sore throat.

  • Swollen lymph nodes in the neck or armpits.

  • Muscle pain.

  • Pain without redness or swelling in a number of joints.

  • Intense or changing patterns of headaches.

  • Unrefreshing sleep.

  • After any exertion, weariness that lasts for more than a day.
2. The fatigue must be severe as indicated by the following:
  • Sleep or rest does not relieve it.

  • The fatigue is not the result of excessive work or exercise.

  • The fatigue substantially impairs a person's ability to function normally at home, at work, and in social occasions.

  • Even mild exercise often makes the symptoms, especially fatigue, much worse.
3. The fatigue must be a new, not lifelong, condition with a definite time of onset. Often, the condition first appears as a viral upper respiratory tract infection marked by some combination of fever, headache, muscle aches, sore throat, earache, congestion, runny nose, cough, diarrhea, and fatigue. Typically, the initial illness is no more severe than any cold or flu.

4. The symptoms must persist. In ordinary infections, symptoms go away after a few days, but in CFS, fatigue and other symptoms recur or continue for months to years. Many patients experience symptoms as recurring bouts of flu-like illness, with each attack lasting from hours to weeks.

Note: Other symptoms reported with CFS but not part of the criteria include intolerance to alcohol, irritable bowel syndrome, dry eyes and mouth, impaired circulation in the hands and feet, visual disturbances, and painful periods in women.




WHO GETS CHRONIC FATIGUE SYNDROME?



Prevalence


In studies of large patient groups, between 15% and 27% of people complain of long-term fatigue, but the majority of these cases are explained by other medical or psychological problems. According to surveys, chronic fatigue syndrome itself affects over four in every 1000 Americans (.4%) and is considered a serious health problem.


Risk Factors


According to a large 1999 US study, the highest rates of CFS were found among women in general, minority groups (African- and Hispanic-Americans), and people with lower levels of education and occupational status. Chronic fatigue is most often experienced by individuals 40 to 50 years old; it is least prevalent in people under 29 or over 60. This disorder, however, occurs in both sexes and at all ages and in all racial and ethnic groups.

Women. Although CFS occurs much more commonly in women, they do not appear to have more severe symptoms than men with the disorder.

Ethnic Groups. Although previous research reports found that Caucasian women have higher rates of CFS than women from other ethnic groups, reports now indicate that such estimates most likely reflect the greater socioeconomic ability of Caucasian women to receive treatment.

Stress-Related Occupations. One study of nurses found that those who were exposed to poor working conditions and threats of accidents faced a higher risk for CFS symptoms than those without these experiences. This finding suggests, perhaps, that stressful work puts people at higher risk for CFS.

Children. Children and adolescents are not immune to its effects. Most studies indicate that girls are more apt to develop CFS than boys, although one found the incidence of the syndrome to be equal. According to a 1999 study, half of the children and adolescents with CFS also suffer psychiatric disorders, primarily anxiety, but also depression.

Personality and Psychologic Factors. Some researchers suggest that people who are over-achievers may be more susceptible to chronic fatigue because they set impossibly high standards for themselves and CFS allows them to escape from them. Personality and psychological factors do not appear to be a direct cause of CFS but may increase a person's susceptibility to the syndrome after exposure to mental or physical stresses, such as viral infections.


WHAT CAUSES CHRONIC FATIGUE SYNDROME?



General Theories for Chronic Fatigue Causes


Theories abound about the causes of chronic fatigue syndrome. Many physicians still doubt that CFS is an actual disease but believe rather that it 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. And, there are no consistent biologic factors that would allow objective measures, such as blood tests or brain scans, to definitively diagnose CFS.

Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:
  • Genetic factors.

  • Brain abnormalities.

  • A hyper-reactive immune system.

  • Viral or other infectious agents.

  • Psychiatric or emotional conditions.
For example, 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 neurologic and genetic abnormalities may trigger the event. Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific neurologic abnormality that experts can point to with assurance.

Sudden- and Gradual-Onset CFS. One interesting theory is that CFS can be categorized as either sudden- or gradual onset, with each category having different causes. In little over half of patients, the onset is sudden, while the remaining patients have a slow onset. Some experts believe that sudden-onset CFS may be triggered by a virus or neurologic abnormality, while gradual-onset CFS might have a psychologic cause. Supporting this theory was a study that observed that MRI scans of the brains of CFS patients without an accompanying psychiatric problem showed small injuries suggesting either a viral infection or neurologic problem.


Central Nervous System and Hormone Abnormalities


Abnormalities in the central nervous system, including pinpoint spots of brain inflammation and abnormal levels of certain hormones have been reported in a number of patients with CFS, but similar findings have also been found in those without the illness.

Abnormalities in the Hypothalamus-Pituitary-Adrenal Axis. Of particular interest to researchers are higher incidences of 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.

Stress Hormone Deficiencies. 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 psychologic 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, another important neurotransmitter, may play a role in CFS.


Infections


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:
  • One theory referred to as "hit and run" suggests 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.

  • Another theory posits that an abnormal immune response reactivates a virus that had persisted in a latent (inactive) stage after an initial infection.

  • A psychologic response to viral infections occurs in susceptible individuals.
Still, not all CFS patients show signs of infection.

Evidence that Supports a Viral Cause. 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.

  • Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS symptoms.

  • 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.
Evidence that Does Not Support an Infectious Cause.
  • Most cases of CFS occur sporadically, cropping up individually without appearing to be contagious.

  • There is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact.

  • No single virus has been implicated in chronic fatigue syndrome. Well-designed studies of patients who met strict criteria for chronic fatigue syndrome and of patients with idiopathic chronic fatigue have not found an increased incidence of any specific infections.


Immune System Abnormalities


CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system, although there is no consistent pattern. Some components appear to be overreactive, whereas others appear to be underreactive.

Allergies. Some, although not all, studies have reported that a majority of CFS patients have allergies to food, pollen, metals (such as nickel or mercury), or other substances. (Most allergic people, in any case, do not have CFS.) Some research indicates that people with both allergies and emotional disorders, such as anxiety or depression, may be more vulnerable to the effects of the inflammatory response. This is a harmful overreaction of the immune response, which triggers the release of a number of immune factors, that can cause fatigue, joint aches, and fever, which can also affect the hypothalamus-pituitary-adrenal system in the brain.

One theory that may help tie in some of the various factors common to CFS suggests that allergies, stress, and infections may deplete a chemical in the body called adenosine triphosphate (ATP). This chemical stores energy in cells and studies have reported a deficiency in many CFS patients. Supporting this theory was a study in which patients reported reduced CFS symptoms after they took a coenzyme called NADH, which increases ATP levels.

Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis. These disorders also have early symptoms resembling CFS. Common to such diseases are the presence of high levels of autoantibodies, antibodies that attack the patient's own cells. Some studies are finding high levels of autoantibodies directed against substances in cell nuclei in CFS patients. Others, however, have found no evidence of an autoimmune factor.

Overactive Immune System. 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.

Deficiencies in Natural Killer Cells. Other studies have indicated lower amounts of so-called natural killer cells in many CFS patients, which might make them more susceptible to viruses.


Neurally Mediated Hypotension


Some studies have observed that a subgroup of patients who fit the strict criteria for chronic fatigue syndrome also have a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when standing up, even for as short a time as ten minutes. It is the result of an abnormality in the central nervous system that signals the heart to slow down and lower blood pressure when a person stands up. Blood pools in the feet and legs before circulating back up to the heart. Its immediate effect can be light-headedness, nausea, and fainting. Some experts posit that a virus or infection may cause injury to the central nervous system that results in NMH. One 1999 study suggested that patients with NHM-associated chronic fatigue syndrome tend to be younger and to recover from CFS sooner than patients whose symptoms are not related to NMH. A less severe hypotension condition known as postural orthostatic tachycardia syndrome (POTS) is also associated with CFS. Not all CFS patients experience NMH and, in fact, one 2001 twin study found no higher incidence of NMH in chronic fatigue patients. Major studies need to be done and the results repeated with larger patient groups before they can be applied to the majority of CFS patients.


Physical Deconditioning and Disturbed Circadian Rhythms


Some experts believe that CFS is a disorder of the sleep-wake cycle (the circadian rhythm). Some argue that this disruption may be precipitated by some mentally or physically stressful event, such as a virus. CFS patients are unable to reset their natural rhythm, which then results in a perpetual cycle of sleep disturbances. According to one theory, this causes avoidance of activity that in turn leads to physical debilitation, which is the primary cause of CFS symptoms. Nevertheless, some studies, including one in 2001, observed that CFS patients are no more physically unfit than sedentary non-CFS peers. The results of these studies indicate then that CFS is not the result of physical unfitness, but that the limited level of activity among CFS is due to the fatigue and symptoms of disease itself.


Psychosocial Factors


Psychological, personality, and social factors are strongly associated with chronic fatigue in most, but not all patients. The complex relationship between physical and emotional factor has yet to be fully understood, however. Psychologic factors are unlikely to be a primary cause of CFS, but they may play a role in increasing susceptibility to onset or perpetuation of the disorder. In many cases, CFS also promotes psychologic and social dysfunction.


Other Theories


Muscle Defect. Patients with CFS sometimes complain that they feel so weak that it seems as if their muscles are no longer working properly. It has been proposed that a defect in skeletal muscle could be the cause of the fatigue. However, physical, chemical, and metabolic studies have not found any consistent pattern of abnormalities in the muscles of these patients.

Hyperventilation. Another theory to account for some cases of chronic fatigue syndrome is hyperventilation, the tendency to "over-breathe," which can be caused by many conditions, including asthma, hyperthyroidism, infections, and anxiety disorder. Chronic hyperventilation can cause an imbalance in oxygen and carbon dioxide, which may produce chest pain, faintness, numbness in the fingers and toes, and motor impairment. In one study, although a significant number of CFS patients experienced hyperventilation, there were no differences in CFS symptoms between patients with hyperventilation and patients who did not experience it. Hyperventilation is very unlikely to be a cause of many instances of chronic fatigue.

Abnormalities in the Vagus Nerve s. One study found that after CFS patients exercise, they exhibit slight abnormalities in the activity of the vagus nerves on the heart. (The vagus nerves run down each side of the neck and end at the intestines and affect many bodily functions.)

Mutations in Mitochondria. One theory about the cause of CFS, as well as fibromyalgia and other illnesses, concerns mutations of the mitochondria, the part of each cell that supplies energy. Inherited disorders involving mutations that affect mitochondria are known to cause fatigue and muscle pain. One study reported that a specific genetic mitochondrial mutation called cytochrome b was associated with intolerance to exercise and aches and pains in a group of patients who had no known family history of mitochondrial genetic disease. In such cases, the mutation might have been due to environmental assaults, such as viruses. More work is warranted on this interesting observation to determine if such a mutation may account for some cases of CFS.


Gulf War Syndrome and Chronic Fatigue


An estimated 90,000 Gulf War veterans have reported symptoms resembling chronic fatigue syndrome, with 6% having severe cases. Women veterans had three times the risk as men. Interestingly, 15% of the noncombat personnel representing the general population, reported the same problems, although the cases in general were less severe than in the veterans.

Symptoms of Gulf War Syndrome. Persian Gulf War veterans have been intensively studied because of a high percentage reporting symptoms that are similar to those in CFS. They include:
  • impaired thinking,

  • confusion and lack of coordination,

  • joint and muscle pain,

  • fear of doing simple tasks,

  • fever, and

  • weakness and incontinence.
Possible Causes of Gulf War Syndrome. Researchers in 2000 reported evidence of injury to nerve clusters in the left side of the brain in Gulf War Veterans with CFS symptoms, which support chemical based injury. Among the theories for the cause of such injuries or why certain veterans were susceptible to it are the following:
  • During this period, many veterans were exposed to a number of environmental toxins, including oil-well fires, pesticides, insect repellents, pyridostigmine bromide (a drug used to prevent injury from nerve gas), depleted uranium used in tank armor and ammunition, and other harmful chemical agents. A survey of 20,000 troops who were within 50 miles of stockpiles of the nerve gas sarin reported no higher incidence of serious nerve injury.

  • Some studies have heavily implicated multiple vaccinations given to military personnel during the Gulf War (but not those given before). In addition some specific vaccines, such as anthrax or botlinum, may have adverse long-term effects. Some researchers suspect that the symptoms were caused by an experimental vaccine that contained a substance called squalene. High levels of antibodies to this compound have been found in the blood of veterans with CFS symptoms.

  • More than a dozen different illnesses have been detected in over 70,000 soldiers examined for this problem. Some researchers identified an unusual bacteria-like organism known as Mycoplasma fermentans in nearly half the veterans who suffered from Gulf War syndrome, and one scientist speculated that it might have been developed from biological warfare.

  • Some experts suspect that post-traumatic stress syndrome (PTSS) may be responsible for the symptoms in some cases. Because PTSS may weaken the blood-brain barrier, some experts believe this weakened barrier may allow agents, such as small viruses, to pass into the brain causing damage and triggering CFS symptoms.
One study reported that the incidence of hospitalization and death was no higher in these veterans than in soldiers who had not been stationed in the Persian Gulf, but this only proves that the symptoms are not fatal or severe enough to send a patient to the hospital. The study does not disprove the condition itself. Whether uncovering the causes of the syndrome in Gulf War soldiers can be applied to civilian cases of CFS, however, is not known.


HOW IS CHRONIC FATIGUE SYNDROME DIAGNOSED?



Personal and Medical History


A physician should first take a careful personal and family medical history, which may include a psychological profile, as well as perform a thorough physical examination. Patients should be prepared to answer certain questions:
  • When did the fatigue first begin?

  • Does anything make it worse or better?

  • Is it better at certain times of the day?

  • Does physical activity make it worse?

  • Are there any other symptoms?

  • Has anyone else in the family ever complained of fatigue?

  • Is your personal and professional life stressful?
The physician may also ask about any changes in weight or request a patient to monitor morning and afternoon body temperatures. The patient should report any drugs being taken, including vitamins and over-the-counter or herbal medications.


Laboratory Tests


Inexpensive tests, including thyroid and liver function tests, blood count, and sedimentation rate, are typically recommended to rule out specific conditions causing persistent fatigue. No blood, urine, or other laboratory test can specifically diagnose CFS. If any are abnormal, they are not useful for diagnosing chronic fatigue syndrome specifically and the physician should look for other causes of these abnormalities.


Investigative Tests


In academic centers where CFS is studied, a series of tests may be performed to measure immune factors or specific proteins or substances that may eventually prove to be causes or markers of chronic fatigue syndrome. For example, a urine test detecting high levels of 5-HIAA, a product of the neurotransmitter serotonin, may prove to be a reliable diagnostic tool for CFS. Of particular interest is an enzyme called RNase L, which is part of the immune defense system and degrades genetic material in viruses. In one study 88% of CFS patients had a specific form of this enzyme that only 28% of non-patients had.


Psychological Profiling


Psychological profile testing may be suggested. Since many insurance policies do not cover this testing, the patient may want to determine the cost beforehand (usually less than $200).


Tilt Test for Neurally Mediated Hypotension


Simply measuring blood pressure will not identify CFS patients whose condition might be caused by neurally mediated hypotension (an abnormal drop in blood pressure). A tilt test, whereby an individual lies on a table tilted upright at a 70-degree angle for a prolonged period, may confirm CFS caused by neurally mediated hypotension if the patient feels lightheaded, sick, and faint after several minutes.


Identifying Conditions That Rule Out Chronic Fatigue Syndrome


Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:
  • depression,

  • infections,

  • pregnancy,

  • extreme exercise, and

  • excessive stress.
In most of these cases, fatigue can be relieved with adequate rest. It is important to note that persistent fatigue can be the harbinger of a serious medical or psychological problem. A number of more serious conditions may cause persistent fatigue and other symptoms of CFS and should be ruled out. Patients and physicians should not overlook these diseases, even if they have been previously treated, but which may not have completely resolved or may cause residual fatigue. Physicians can usually distinguish these diseases from CFS after a clinical evaluation and laboratory testing.

Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis is marked by fatigue and swollen glands. It primarily affects adolescents and young adults. Some patients may have lingering fatigue that last for many months and blood tests that indicate a persistence of the Epstein-Barr virus (EBV), which causes mononucleosis. At one time, based on these cases, some experts believed that EBV would turn out to be the cause of chronic fatigue syndrome. However, many healthy persons without CFS have the same signs of low-level EBV infection, and, conversely, many patients with CFS show no signs of EBV infection. Because of these and other findings, researchers generally do not believe there is any direct link between Epstein-Barr virus infection and CFS.

Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, are caused by autoimmunity, a condition in which the person's immune system attacks the body's own tissues. The early symptoms of these conditions may mimic some of those that appear in CFS, such as muscle and joint pain and fatigue. These diseases, like CFS, also occur more often in women than in men. Autoimmune diseases evolve slowly, and even if a diagnosis of chronic fatigue syndrome is considered, physicians should keep track of any changes in symptoms over time in order to rule out these serious illnesses. (It should also be noted that some experts are concerned that many patients who actually have CFS will be mistakenly diagnosed with these diseases, particularly multiple sclerosis, and subjected to unnecessary treatments.)

Post-Lyme Syndrome. A delayed response or recurrence of previously treated Lyme disease (called post-Lyme syndrome) may be mistaken for chronic fatigue syndrome. Although the two disorders are similar, one study found that CFS patients reported more flu-like syndromes and those with post-Lyme disease performed significantly worse on tests of mental functioning and motor control. If CFS patients are mistakenly diagnosed and treated for Lyme disease, they may take prolonged courses of antibiotics that induce resistance to the antibiotics, ultimately doing more harm than good.

Psychosis and Severe Mental Disorders. The Centers for Disease Control, which set up the definitions in the US for research in chronic fatigue syndrome, recognize depression as one of the symptoms of CFS, but rule out chronic fatigue syndrome as a diagnosis for anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia. Depression or anxiety not associated with a psychosis or severe mental illness does not rule out CFS.

Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and be confused with CFS:
  • Sleep apnea is a common disorder that can cause daytime fatigue without the patient being aware of the problem. This is actually a breathing disorder often marked by loud snoring and thrashing in bed. A person may not realize the problem exists unless it is brought to his or her attention by a sleeping partner or observer.

  • Narcolepsy is a peculiar and rare disorder in which a person suddenly falls asleep without any previous signs of fatigue.

  • Other sleep disorders that cause daytime fatigue include insomnia and restless legs syndrome.
[For more information on sleep disorders , see the Reports Insomnia, Leg Disorders, and Narcolepsy .]

Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more of CFS symptoms including arthritic symptoms, fever, and fatigue [ see Table, below].

Other Diseases that Cause Joint Pain, Muscle Aches, or Both

Disease

Specific Subtypes

Osteoarthritis



Rheumatic Autoimmune Diseases

Rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis) Behcet's disease

Infectious Arthritis

Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis

Postinfectious or Reactive Arthritis

Reiter's syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease

Crystal Induced Arthritis

Gout and pseudogout

Fibromyalgia (Does not necessarily rule out accompanying CFS)



Other Diseases

Hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis



Other Medical Conditions that Usually Rule out CFS. Many diseases, both benign and serious, can fully explain prolonged or chronic fatigue, including hepatitis, anemia, infections, various forms of cancer, neuromuscular diseases (such as myasthenia gravis), hypothyroidism, and diabetes.

Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by the weight. People who are obese are also at particular risk for sleep apnea, which can confuse the diagnosis.

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependency on or abuse of alcohol or illicit drugs may manifest as chronic fatigue. Medications should be considered as a possible cause of fatigue if an individual has recently started, stopped, or changed medications. Withdrawal from caffeine can produce depression, fatigue, and headache.


Conditions That Do Not Rule Out Chronic Fatigue Syndrome


Many diagnosable conditions cause symptoms similar to CFS but they can overlap and so their presence does not necessarily rule CFS out as a co-disorder. In fact, CFS patients appear to be at high risk for developing additional health problems, particularly those with similar symptoms (eg, fibromyalgia, irritable bowel syndrome, chronic pelvic pain, chemical sensitivities, and temporomandibular disorder). Some tests may be positive for other diseases that cause CFS-like symptoms but if the results are ambiguous or weak, CFS should not be ruled out. If a physician can verify that another similar disease has been treated adequately but symptoms of chronic fatigue still persist, then CFS may be present.

Fibromyalgia. Fibromyalgia causes prolonged fatigue and widespread muscle aches and is the disease most often confused with CFS. In fact, many experts believe fibromyalgia is simply another variant of chronic fatigue syndrome. One researcher compared the relationship of fibromyalgia to chronic fatigue as that of migraine to headache.

A characteristic feature of fibromyalgia is the existence of at least 10 distinct sites of deep muscle tenderness that hurt when touched firmly. The sites often include the following:
  • the side of the neck,

  • the top of the shoulder blade,

  • the outside of the upper buttock and hip joint, and

  • the inside of the knee.
Some patients with CFS exhibit similar tender pressure points. Recurrent sore throat, headache, low fever, and depression are also common symptoms of fibromyalgia. Like CFS, fibromyalgia is chronic and not curable. [For more information, 76, Fibromyalgia.]

Depression and Anxiety. The link between psychological disorders and chronic fatigue syndrome is problematic because so many of the symptoms overlap. A number of physicians, in fact, believe that chronic fatigue is not a physical illness but can be attributed to emotional disorders, particularly depression. In any case, the relationship between CFS and emotional disorders is highly interrelated. Many patients who are diagnosed with CFS report having felt depressed before the onset of chronic fatigue. Many other CFS patients, however, felt alert and mentally healthy before the onset of CFS symptoms. Many of these previously healthy patients become depressed and anxious because they feel so exhausted all the time. CFS may also lead to highly stressful socioeconomic situations, such as social isolation and poverty, that can contribute to and even cause emotional disorders in susceptible individuals, which in turn can worsen CFS.

Depression, in any case, is very common in the general population, affecting up to a fifth of all Americans at some point in their lives, and most depressed people feel fatigued. Unlike ordinary periods of sadness, an episode of depression can last many months. Symptoms of major depression include the following:
  • a depressed mood every day,

  • significant weight gain or loss (of 10% or more of an individual's typical body weight),

  • insomnia or excessive sleeping,

  • restlessness or a sense of being slowed down.

  • low energy every day,

  • worthless or inappropriately guilty feelings.

  • an inability to concentrate or to make decisions,

  • suicidal thoughts.
Major depression is likely to be the responsible condition in the presence of several of these symptoms and in the absence of physical symptoms (such as sore throat, aches and pains, or fever). And the longer fatigue has continued without such physical symptoms, the more likely the diagnosis is depression.

A persistent form of minor depression called dysthymia, however, may be more difficult to differentiate from CFS and may actually account for a subset of CFS cases. Dysthymia is characterized by many of the same symptoms that occur in major depression but they are less intense and last much longer, at least two years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities. [For more information, 8, Depression.]

Other Conditions that Do not Rule out CFS. A number of other conditions also often co-exist with CFS and, in fact, occur at higher-than-average rates among CFS patients:
  • temporomandibular disorder (TMD),

  • irritable bowel syndrome,

  • •chronic headaches,

  • interstitial cystitis,

  • hypothyroidism,

  • Sjögren's syndrome.
Certain other conditions can also co-exist with CFS. For example, chronic fatigue and pain can be caused by exposure to various chemicals and environmental toxins, such as solvents, pesticides, or heavy metals (cadmium, mercury, or lead, for example).


HOW SERIOUS IS CHRONIC FATIGUE SYNDROME?



Severity of Physical Symptoms


The physical severity of chronic fatigue syndrome varies:
  • In extreme cases, patients are bedridden and can do virtually nothing, including even light housework.

  • Most commonly, patients with CFS report that they have trouble fulfilling both home and work responsibilities. CFS sufferers typically work part-time.
Studies may under-report the severity of the condition because severely disabled patients may have difficulty getting to and from sites where studies are being conducted and so would not be able to participate. Some medical centers, in fact, do not accommodate the disabled CFS patients with the same consideration or resources (eg, wheelchairs, beds) that would be given patients with more identifiable disorders, such as multiple sclerosis.


Mental Incapacity


Most patients say that while fatigue is the most incapacitating symptom, those of mental impairment, such as an inability to concentrate, are the most distressing. The effects of CFS on mental functioning are complex:
  • Some studies indicate that although general intelligence is not impaired, CFS patients test lower in certain mental functions, particularly speed and efficiency in processing complex information. In such studies, this impaired mental function occurs regardless of the presence or absence of depression or other psychiatric disorders.

  • One study found that the mental impairment in CFS patients parallels the degree of their physical impairment, indicating that the disease process itself may exert a neurologic effect.

  • Some studies indicate that there is very little measurable difference in memory, information processing, and concentration between CFS patients and those without the disorder. Some experts argue that the perceived differences in mental functioning are due to emotional problems. (Mental tests used in studies are usually performed in a doctor's office or clinical setting, however. Positive results then may not accurately reflect the burden that daily tasks place on severely fatigued patients and which result in little spare capacity for attention or mental flexibility.)


Long-Term Outlook in Adults


Because the illness has been undefined and there are few objective measures for recovery, experts have found it difficult to determine the long-term outlook of CFS. Some studies have reported that between 58% and 72% of patients who complain of chronic fatigue (whether CFS or idiopathic fatigue) continue to experience it after a year and in one study nearly 60% were still fatigued at two years. Even if patients get progressively worse, however, the disorder is not fatal and patients can expect a normal life span. The outlook for specific individuals my depend on certain factors.

Sudden or Gradual Onset. Some studies have observed that patients whose symptoms began abruptly following a severe viral illness recovered completely after six months to a year, whereas patients whose problems developed slowly and insidiously experienced symptoms for a longer period of time.

Severity of CFS. Many patients with moderate chronic fatigue have reported turning a corner after a year or two and slowly regaining energy despite some setbacks along the way. One small 1999 study observed that even after four years few patients with severe CFS had returned to their pre-illness state. It should be noted, however, that in another study, patients with severe CFS who were treated with a multidisciplinary rehabilitation program, nearly all improved significantly and the gains were maintained for at least a year afterward.

Signs of Positive Outlook. According to one study, CFS patients who are more likely to experience improvement over time have the following positive signs:
  • Can think clearly most of the time.

  • Have no other physical or emotional complaints beyond CFS symptoms.

  • Sleep well.


Outlook in Children


Although children with symptoms of chronic fatigue have not been rigorously studied, some studies indicate that children generally have a better prognosis than adults and recover after one to four years in between two-thirds and 95% of cases.


WHAT LIFE STYLE MEASURES CAN HELP MANAGE CHRONIC FATIGUE SYNDROME?



Exercise


One study found that 75% of patients who were able to engage in exercise, particularly aerobic exercise, reported improvement in fatigue, normal functioning, and fitness after a year. Unfortunately, CFS patients have a lower exercise capacity than healthy individuals, and in fact over-exercising can intensify symptoms. Some patients experience profound fatigue following even modest exercise. It is the primary factor in the low-activity levels in these patients.

The following tips may be helpful when embarking on an exercise program:
  • Start slowly and incrementally, beginning with as little as three to five minutes of moderate exercise a day. The goal is to increase activity by about 20% every two to three weeks. (Capacity varies greatly among CFS sufferers, however, and some may not be able to achieve this.)

  • Establish limits and keep within them in order to avoid overexertion and relapse.

  • Experiment with different forms of physical activity that suit available energy levels. Some patients report great benefits from Yoga or Tai chi, which combine exercise with meditation.

  • Setbacks will occur, but patients should not become discouraged.


Diet


Chronic fatigue syndrome patients should be sure to maintain a healthy diet that includes the following:
  • Plenty of fresh dark-colored fruits and vegetables, which are rich in antioxidants.

  • Fiber-rich foods.

  • Some fats may be beneficial, but avoid saturated fats (found in animal products). A few studies reported some improved symptoms in patients who consumed black currant and fish oils (sold in supplement form as EPA-DHA omega 3). These oils contain a fatty acids that help block certain immune factors responsible for damaging inflammation.

  • For those with demonstrated low blood pressure, increasing the amount of salt in the diet may be helpful.


Stress Reduction Techniques


One panel of experts concluded that relaxation and stress-reduction techniques were helpful in managing chronic pain. They also can help relieve the stress associated with the disease. They are not useful, however, as the primary treatment for CFS. A number of relaxation techniques are available:
  • deep breathing exercises,

  • muscle relaxation techniques,

  • meditation,

  • hypnosis,

  • biofeedback, and

  • massage therapy.
[For more information, 31 Stress.]


Personal Relationships


Strong, supportive, relationships with family and friends may be an important factor in the overall improvement of CFS patients. It should be strongly noted, however, that many CFS patients are overly dependent and should not impose expectations that cannot be met on loved ones. Ongoing support groups with fellow patients may very helpful. In one 2001 study, sharing experiences in a group therapy setting proved to be the most valuable component and one that improved patients' sense of coherence and coping abilities.


Alternative Therapies


Because of the difficulties in treating chronic fatigue syndrome, many patients seek alternative therapies. Some, such as acupuncture and relaxation techniques, may be helpful and are not dangerous. No scientific evidence exists that vitamin and mineral supplements will relieve CFS, but taken in moderation, they are usually not harmful. A number of herbal medicines have been used for chronic fatigue syndrome. Most have not proven to be effective and some may even be harmful [See Warning Box.] One positive study concerned St. John's Wort, which is being investigated for mild depression. In the study, the herbal agent improved fatigue in CFS patients, even in those who did not consider themselves to be depressed.


Warnings on Alternative and So-Called Natural Remedies


It should be strongly noted that alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication. Most problems reported occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals. Even if studies report positive benefits, most, to date, are very small. In addition, the substances used in such studies are, in most cases, not what are being marketed to the public.

CFS patients should be wary of those that promise a cure or urge the purchase of expensive but useless and sometimes potentially dangerous treatments, such as the following:
  • Hydrogen peroxide injections (which can cause blood clots or strokes).

  • Megadoses of vitamins (which can be toxic). Supplements of folic acid, vitamin B12, and vitamin B15 (also called pangamic acid) have shown no benefit.

  • High colonic enemas.

  • Bee pollen (which can cause an allergic reaction).

  • Injections of liver extract, or superoxide dismutase (SOD).

  • Of particular note for CFS patients is the product Nature's Nutrition Formula One; it includes the ingredient Ma Huang, which contains the stimulants ephedrine, and kola nut, a caffeine source. Serious adverse reactions, including seizures, psychosis, and several deaths, have been reported in people taking this supplement for increased energy or weight loss. Products that have only one of these ingredients appear not to have the same effect, but people should take so-called energy boosting supplements only with the knowledge and recommendation of their physician.
The following website is building a database of natural remedy brands that it tests and rates. Not all are available yet. http://www.ConsumerLab.com/

The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins (call 800-332-1088).




HOW IS CHRONIC FATIGUE SYNDROME TREATED?


Diagnostic

The criteria used for studying CFS are very helpful, particularly if the patient does not have any accompanying disorder, such as depression or arthritis, that could complicate the diagnosis. They are not used, however, on specific diagnosis of individuals. [See Box Criteria for Studying CFS.]

There is no proven or reliable cure for CFS, and no drug has been developed specifically for this disorder. Patients with the best chance for improvement are those who remain as active as possible and who seek to have some control over the course of the disorder. Patients should seek physicians who are willing to consider the problem as a medical condition with psychiatric components. They should be very wary, however, if the physician recommends excessive and expensive treatments that may have serious adverse effects and that have no proven benefits. For patients with severe CFS that cannot be managed with lifestyle changes and standard medications, asking the physician about enrolling in any available clinical trials may be helpful. Little significant research, however, is being conducted on treatments for CFS. For example, there were no major trials on drug therapies on either CFS or fibromyalgia reported during 2000.


Cognitive-Behavioral Therapy


In one study, CFS patients who reported the severest symptoms also believed they had the least control over them. Cognitive behavioral therapy is designed to help patients control symptoms and is proving to have substantial benefits for these patients. In fact, some experts believe that patients who are diagnosed with CFS should immediately be referred to therapists trained in cognitive behavioral therapy. (Psychoanalysis and other interpersonal psychological therapies, which are concerned with subconscious thoughts and early childhood memories, are not generally helpful for the patient with chronic fatigue syndrome.)

The Goals of Cognitive-Behavioral Therapy. The primary goals of cognitive-behavioral therapy are to change any distorted perceptions that individuals have of the world and of themselves and to change their behavior accordingly. For CFS patients, this means learning to think differently about their fatigue and to improve their ability to deal with stressful situations and manage their disorder. Cognitive therapy is particularly helpful in defining and setting limits, behaviors that are extremely important for these patients.

The Procedure . Cognitive therapy may be expensive and not covered by insurance, although it is usually of short duration, typically six to 20 one-hour sessions. Patients are also given homework, which usually includes keeping a diary and attempting tasks that they have avoided because of negative thinking.

A typical cognitive therapy program may involve the following measures:
  • Keep a Diary. The patient is almost always asked to keep an energy diary, which can be a key component of CFS cognitive therapy. The diary serves as a general guide for setting limits and planning activities. The patient uses the diary to track any factors, such as a job or a relationship, that may be making the fatigue worse or better. It is also used to track the times of day when energy levels are at their highest and lowest peaks.

  • Adjust Schedule. The patient adjusts schedules to conform to energy peaks and valleys recorded in the diary. For instance, the patient may plan low-energy times for taking a nap and high-energy times for planning important activities. Developing fairly rigid daily routines around probable energy spurts or drops may help establish a more predictable pattern.

  • Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs ("eg, I'm not good enough to control this disease, so I'm a total failure.") to using coping statements ("Where is the evidence that I can control this disease?")

  • Be Flexible. Energy levels will most likely never be entirely predictable. Patients must also be prepared to adapt to energy variations. Instead of a long nap, for instance, patients may need five to 10 minutes rest periods every hour or more, during which time relaxation or meditation methods are useful.

  • Set Limits. Limits are designed to keep both mental and physical stress within a manageable framework so that patients do not get discouraged by forcing themselves into situations in which they are likely to fail. For example, tasks are broken down into incremental steps and patients focus on one at a time.

  • Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.

  • Manage Impaired Concentration. Patients seek out activities that are appealing, focus attention, and help increase alertness. They learn to request instructions given as concise simple statements. External distractions, such as music or talking, are kept to a minimum.

  • Accept Relapses. Over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of treatment- or self-failure.
Using both self-observation and specific tasks, patients gradually shift their fixed ideas that they are helpless against the fatigue that dominates their lives to the perception that fatigue is only one negative and, to a degree, a manageable experience among many positive ones.

Success Rates. The following are some studies reporting results on the cognitive therapy approach:
  • In one study comparing patients receiving standard treatment with those receiving the same treatment plus cognitive therapy, 73% of the cognitive group were spending less time in bed and functioning normally after a year, as opposed to only 27% of those who received standard therapy.

  • In another study, 70% of patients improved significantly after six months of cognitive therapy, compared to 19% who used only relaxation techniques.

  • A 2001 study found that patients' symptoms of fatigue and daily functioning improved significantly more after cognitive therapy than with guided support groups.

  • Some experts believe that this approach may be particularly important for victims of Gulf War syndrome, whether or not the cause turns out to be the same as for CFS or nerve gas toxins since there are no other proven treatments for either condition.
Not all studies support the benefits of cognitive therapy; the skill of the therapist is very important in its success. It is important to note that even if chronic fatigue syndrome proves to have a specific organic cause, the power of the mind to improve or oppose health problems is significant, and treatments that promote a positive outlook are beneficial for any disease.

Supported Graded Exercise

In one 2001 study, patients were provided with medical reports suggesting that their disorder was due to a physiologic disruption of their biologic rhythms, which led to inactivity and caused a cycle of poor physical condition and CFS symptoms. They were then encouraged to engage in a self-managed graded exercise program. Over 80% of patients reported improvement in many symptoms. The benefits persisted for at least a year, although 32% of patients still complained of fatigue at the end of this period. In the study, this approach was less expensive and as successful as cognitive behavior therapy. It should be noted, however, that no proof exists that CFS is caused by physical unfitness, and, in fact, a number of studies suggest that CFS limits exercise and causes poor conditioning. Excessive exercise can even exacerbate symptoms. Opponents of the study also argue that the subjects were not selected according to the latest criteria for CFS and many may simply have depression-related fatigue. There were also other methodological problems. Still, the improvement experienced by many patients warrants further study. [Also see Exercise under What Life Style Measures Can Help Manage Chronic Fatigue Syndrome?]


Antidepressant Drugs


Because of the association between depression and CFS, antidepressants are often tried with varying degrees of success, depending on the type:
  • Tricyclic Antidepressants. Antidepressants known as tricyclics may be particularly helpful for CFS patients. For example, the tricyclic amitriptyline (Elavil) is known to relieve many of the symptoms of CFS, including sleeplessness and low energy levels. Improvement in symptoms can take three to four weeks. Other tricyclics include doxepin (Sinequan), desipramine (Norpramin), nortriptyline (Pamelor), clomipramine (Anafranil), and imipramine (Tofranil, Janimine). These agents can have severe side effects, although patients with CFS normally respond to much lower doses than those used to treat people with depression. In fact, many CFS patients cannot tolerate the higher doses commonly used to treat the psychiatric disorder. Like all medications, tricyclics must be taken as directed; overdose can be life threatening.

  • Monoamine Oxidase Inhibitors (MAOIs). Monoamine oxidase inhibitors (MAOIs) block the enzyme monoamine oxidase, which has negative effects on many of the neurotransmitters that are important for well being. In one study moclobemide, a newer MAOI, was associated with improved energy levels in CFS patients regardless of whether they are depressed or not. Other MAOIs are likely to have similar effects. The most serious side effect of MAOIs is severe hypertension, which can be brought on by eating certain foods having a high tyramine content. Such foods include aged cheeses, most red wines, sauerkraut, vermouth, chicken livers, dried meats and fish, canned figs, fava beans, and concentrated yeast products. They also have serious interactions with a number of medications and should not be taken by pregnant women.

  • SSRIs. The popular antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) appear to have little value for CFS beyond treating any accompanying depression. They include fluoxetine (Prozac), sertraline (Zoloft), and Paroxetine (Paxil).

  • Designer Antidepressants. Newer, so-called designer SSRIs, including nefazodone (Serzone) or mirtazapine (Remeron) affect combinations of different neurotransmitters, and some may have moderate benefits for CFS patients. For example in one study nefazodone improved mood, fatigue, and sleep disturbances.
Common side effects of many antidepressants include dry mouth, restlessness, reduced sexual drive, a slightly increased heart rate, and constipation. Virtually all antidepressants have complicated interactions with other drugs, some are very serious. [For more details on these agents, 08, Depression.]


Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)


Nonsteroidal anti-inflammatory drugs (NSAIDs) are common pain relievers that reduce inflammation. They include, among many others, aspirin, ibuprofen (Motrin, Advil, Nuprin, Rufen), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). Although NSAIDs can work very effectively against symptoms, long term use can trigger gastrointestinal problems such as upset stomachs, ulcers, and internal bleeding. [ See Box Ulcer Risk for Specific NSAIDs.]

NSAIDs can also increase blood pressure, particularly among people already being treated for hypertension. About 12% to 15% of elderly people take both an NSAID and an antihypertensive drug. Piroxicam, naproxen, and indomethacin appear to pose the greatest risk of high blood pressure. Sulindac has the smallest effect.

Other side effects of NSAIDs include dizziness, ringing in the ears, headaches, skin rashes, and possibly depression. Studies have appeared suggesting that high doses of NSAIDs can damage cartilage, and there have also been reports that NSAIDs can cause kidney damage (which, however, resolves once the patient stops using the drug). People with high blood pressure, severe circulation disorders, or kidney or liver problems, as well as people taking diuretics or oral hypoglycemics, must be closely monitored if they need to use NSAIDs on a long-term basis. Because NSAIDs reduce blood clotting, NSAID users scheduled for surgery should stop taking those drugs a week before the operation.


Ulcer Risk for NSAIDs


Who's at Risk? In the US the effects of NSAIDs are responsible for more than 100,000 hospitalizations and 16,500 deaths each year. Research has suggested that 7.3 of every 1000 osteoarthritic patients who regularly take NSAIDs will suffer a major gastrointestinal complication in the course of a year. The elderly, smokers, and alcohol abusers are at particular risk for such complications. The risk for bleeding is continuous for as long as a patient is on these drugs and may even persist for about a year after taking them. Although short courses of NSAIDs for temporary pain relief should not cause major problems, of concern was a 1998 study indicating that taking NSAIDs for only six months posed a risk for symptomatic ulcers that was greater than 1%. Regular use of even over-the-counter NSAIDs may be hazardous to anyone.

One study ranked the sixteen most commonly used NSAIDs according to risk for ulcers and bleeding.
  • Lowest risk: nabumetone (Relafen), etodolac (Lodine), salsalate, and sulindac (Clinoril).

  • Medium risk: diclofenac (Voltaren), ibuprofen (Motrin, Advil, Nuprin, Rufen), aspirin, naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and tolmetin (Tolectin). Drugs within this group vary in risk. Studies show, for example, that short-term use of naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding. Although ketoprofen (Actron, Orudis KT) was considered a medium-risk drug, another study reported that even one week of taking the drug at low doses causes significant GI injury.

  • Highest risk: flurbiprofen (Ansaid), piroxicam (Feldene), fenoprofen, indomethacin (Indocin), meclofenamate (Meclomen), and oxaprozin.
Drugs Used to Protect Against NSAID-Induced Ulcers. Some agents available to protect against NSAID-induced ulcers include the following:
  • Proton-pump inhibitors are the first choice for preventing ulcers in high-risk individuals. They are well tolerated and may even heal existing ulcers. Such drugs include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprozole. They may reduce NSAID-ulcer rates by as much as 80% compared with no treatment.

  • Misoprostol is a prostaglandin, the protective substance blocked by NSAID use. It is used to prevent NSAID-induced ulcers, both duodenal and gastric, but is not useful in healing existing ulcers. (Arthrotec is a combination of misoprostol and the NSAID diclofenac. One study found that patients taking Arthrotec had 65% to 80% fewer ulcers than those who took NSAIDs alone.


COX-2 Inhibitors


Celecoxib (Celebrex), rofecoxib (Vioxx), and meloxicam (Mobic) are known as COX-2 (cyclooxygenase-2) inhibitors, the so-called super-aspirins. Standard NSAIDs block two enzymes called cyclooxygenase 1 and 2 (COX-1 and -2). The new drugs block COX-2 (responsible for most inflammatory effects) but not COX-1 (which normally protects the stomach).

Short-term studies comparing them to a number of NSAIDs are indicating that they may be as effective and less harmful to the GI tract than NSAIDs. Theoretically, they may even have properties that produce less adverse effects on cartilage than NSAIDs may have. Some studies have found that patients taking COX-2 inhibitors have the same gastrointestinal symptoms (eg, diarrhea, abdominal discomfort) as standard NSAIDs. (Other side effects found with short-term use include headache and dizziness.) Nevertheless, studies that have actually examined patients for ulcers have found far fewer with the use of the COX-2 inhibitors. Importantly, a 2000 well-controlled study of celecoxib reported a lower incidence of ulcers and other toxic side effects than in patients taking ibuprofen or diclofenac. One 1999 study even found that the rate of GI problems with celecoxib was equal to that in people who do not take NSAIDs at all.

Still, long-term side effects are unknown, and some researchers theorize that inhibiting COX-2 may have some negative as well as positive results. One 2000 study observed that the COX-2 inhibitors had some adverse effects on kidney function, particularly in elderly people, that were similar to the effects of standard NSAIDs. Patients taking anticoagulant drugs may experience a higher risk for bleeding with the use of these agents. A few cases of psychiatric side effects (hallucinations), fluid build up, high blood pressure, and excess potassium in the blood has been observed with higher doses of celecoxib or rofecoxib. They may have negative effects on pregnancy and fertility; more research is needed to determine this. They are currently more expensive than traditional NSAIDs, and some insurers do not pay for them.


Treatment of Neurally Mediated Hypotension


In one study, 76% of patients diagnosed with and specifically treated for neurally mediated hypotension (NMH) experienced improvement within a month, and in 40% of these patients, chronic fatigue symptoms completely or nearly completely resolved. It should be stressed that no one should take measures to raise blood pressure without a clear diagnosis of NMH or without a physician's approval, since increasing blood pressure can be very dangerous in individuals with existing normal or high blood pressure. There is also no clear evidence yet that NMH is a major cause of chronic fatigue syndrome

Life Style Changes. For treating NHM, the physician might first recommend nonmedicinal measures:
  • Increasing salt content in the diet may be warranted in patients with demonstrated low blood pressure.

  • Caffeinated beverages may be helpful.

  • Perform exercises before getting out of bed that flex the feet so that the blood moves up toward the head.

  • Avoid excessive activity after meals.

  • Special support garments may help to prevent circulating blood from pooling in the lower part of the body and to return it to the heart.
Medications. If the condition does not improve, certain medications may be tried in combination or alone. Midodrine (ProAmatine), for example, increases smooth muscle tone and blood pressure and reduces symptoms of NMH. Adverse effects include itching, numbness, and tingling, but the drug is well tolerated.

A wide range of drugs normally used for other disorders have been used to treat NMH, but physicians have had difficulty adjusting them so that they would be effective for NMH without causing distressing side effects. Such medications include the following:
  • Indomethacin or ibuprofen (nonsteroidal anti-inflammatory drugs or NSAIDs).

  • Disopyramide (an anti-arrhythmic drug).

  • Beta-blockers (drugs normally used to prevent hypertension).

  • Recombinant erythropoietin epoetin alfa (used to increase red blood cells).

  • Fludrocortisone (Florinef), an oral steroid used for low blood pressure, has been tested on CFS subjects with NMH but studies in 2000 and 2001 reported no benefits.


Corticosteroids


Some evidence exists that patients with CFS may be deficient in cortisol, a steroid hormone. Studies testing the steroid drug hydrocortisone have reported increased energy and less fatigue in patients taking it. However, side effects including insomnia, increased appetite, weight gain, and, more seriously, suppression of the adrenal gland, make this therapy unacceptable. One study reporting improvement with very low doses (5 mg to 10 mg daily) with only minor side effects may make this therapy feasible for some patients, but longer-term and larger studies are needed.


Ampligen


The antiviral drug, polyl:polyC12U (Ampligen) is one of the most studied anti-CFS drugs at this time. In an analysis of studies, after 24 weeks of Ampligen therapy patients had a 31% improvement in CFS symptoms compared to a 10% improvement in patients on placebo. Patients taking Ampligen progressed from needing daily assistance of normal activities to needing assistance only once a week. However, many patients have reported adverse effects, and longer studies are needed.


Phototherapy


The use of phototherapy may be effective treatment for patients with CFS whose symptoms have a seasonal variability that is similar to those of patients with seasonal affective disorder (SAD). Patients with SAD experience more depression during winter than summer months. With phototherapy, the patient sits a few feet away from a box-like device that emits very bright fluorescent light (10,000 lux) for about 30 minutes every day. It is best performed immediately after awakening in the morning.


NADH


A natural antioxidant agent called nicotinamide adenine dinucleotide, or NADH (Enada), is also in trials. This substance boosts serotonin and triggers adenosine triphosphate (ATP), a molecule found in every cell and which is necessary for conversion of food into energy. Small studies are reporting improved symptoms in patients taking it even after 18 months. Although the studies are small, these results showed promise.


WHERE ELSE CAN HELP BE FOUND FOR CHRONIC FATIGUE SYNDROME?


Patients with chronic fatigue syndrome are not only physically and emotionally debilitated, but may feel humiliated by their inability to cope with everyday activities. Family and friends are also affected. Even loved ones may react with anger and suspicion instead of the sympathy and support essential for people with this disorder. Fortunately, excellent reputable support associations composed of others who suffer CFS are now available that offer advice, solace, and current information. Patients should be careful, however, of groups or organizations that market products, unproved remedies, and misinformation. The Internet offers invaluable help and support for people with many disorders, but patients should beware of web sites that are sponsored by self-interested groups or companies.

The Chronic Fatigue and Immune Dysfunction Syndrome Association of America, PO Box 220398, Charlotte, NC 28222-0398. Call (800-44-CFIDS or 3437) or on the Internet (http://www.cfids.org)

National Chronic Fatigue Syndrome and Fibromyalgia Association, PO Box 18426, Kansas City, MO 64133. Call (816-313-2000)

This organization is a good source of accurate information on CFS. Send self-address envelope for information. They will return phone calls using a collect call.

American Association for Chronic Fatigue Syndrome, c/o Harborview Medical Center, 325 Ninth Avenue, Box 359780, Seattle, WA 98104. Call (206-521-1932) or on the Internet (http://www.AACFS.org/)

Formed by health professionals to promote dissemination of information on CFS.

Journal of Chronic Fatigue Syndrome (http://www.cfs-news.org/)

Centers for Disease Control and Prevention, Division of Viral Diseases, Building 6, Rm. 120, Atlanta, GA 30333. Call (404-332-4555) or on the Internet (http://www.cdc.gov/ncidod/diseases/cfs/)

American Chronic Pain Association, P.O. Box 850, Rocklin, CA 95677. Call (916) 632-0922 or on the Internet (http://www.theacpa.org/)

National Chronic Pain Outreach Association.

7979 Old Georgetown Road, Suite 100, Bethesda, MD 20814-2429. Call (301) 652-4948, or on the internet at http://neurosurgery.mgh.harvard.edu/ncpainoa.htm

American Pain Society, 4700 W. Lake Avenue, Glenview, IL 60025. Call (847-375-4715) or on the Internet (http://www.ampainsoc.org/)

International Association for the Study of Pain, 909 NE 43rd St., Suite 306, Seattle, WA 98105-6020. Call (206-547-6409) or on the Internet (http://dasnet02.dokkyomed.ac.jp/IASPM/IASP.html)

National Institute of Allergy and Infectious Diseases (NIAID), Office of Communications, Building 31, Rm. 7A50, 31 Center Dr., MSC 2520, Bethesda, MD 20892-2520. Write for the publication Chronic Fatigue Syndrome, NIH Publication No. 96-484

or on the Internet (www.niaid.nih.gov).

http://www.ChronicFatiguesupport.com/

Herb Research Foundation. 1007 Pearl St., Suite 200, Boulder, CO 80302. Call (303) 449-2265, or on the internet, (http://www. herbs.org). A non-profit research institute that sells information on the health effects of herbs.

ConsumerLab, on the internet at http://www.consumerlab.com. Provides research on the quality of herbal products and dietary supplements.

MEDWATCH, a Food and Drug Administration program called for people to report adverse reactions to medical products, including drugs, herbal remedies and vitamins. Call 800-332-1088.

American Association of Medical Acupuncture, 5820 Wilshire Blvd., Suite 500, Los Angeles, CA 90036. On the internet, http://www.medicalacupuncture.org. This organization will provide information about physician acupuncturists in particular areas.

The following Internet site offers many links and many sources of information for those who want a broad selection.

http://www.immunesupport.com/

http://www.cfs-news/

http://www.ahmf.org/

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