CHRONIC FATIGUE SYNDROME

Introduction

Tired, exhausted, worn down - there are times when we have all felt such fatigue, when we do not want to go back to work for a week or two, or wish we could have a month off to rest. But chronic fatigue syndrome differs from the more typical feelings of fatigue. It is a debilitating disorder that interferes with a person's ability to participate in the activities of daily life, sometimes for long periods of time. Even the simplest task can become a hurdle to overcome, and expending just a small amount of energy can put a person right back in bed.

Some of the symptoms of chronic fatigue syndrome are constant tiredness and feeling easily exhausted. There may also be: recurring dull headaches; joint and muscle aches; a feeling of feverishness and chills without high fever; depression; difficulty in concentrating on tasks; and tender lymph glands. Of course, many of these symptoms also occur as part of other illnesses, making chronic fatigue syndrome difficult to diagnose and to categorise.

History

Although the syndrome has only recently been publicised, it is not new, and is probably not increasing in frequency. However the term chronic fatigue syndrome is new. Researchers chose the name because they believe this illness is not a single disease, but results from a combination of several factors. In addition, the name accurately describes the characteristic problems of the disorder without second-guessing the underlying causes. Every time someone has tried to pinpoint a cause in the past, they have been mistaken.

A textbook written in 1750 by an English physician, Sir Richard Manningham, described symptoms of a disease he calls "febricula" or "little fever," which sound strikingly similar to those of chronic fatigue syndrome. People in that era also referred to an illness called the "vapours", characterised by great fatigue.

As early as 1871, physicians began diagnosing exhaustion in soldiers following the stress of battle. This version of fatigue syndrome became known as "soldier's heart", or "the effort syndrome". During World War I some 60,000 of the British forces were diagnosed with the problem, and 44,000 of these were retired from the military because they could no longer function in combat.

In 1934, an American physician, Alice Evans, suggested that chronic fatigue was caused by a bacterial infection transmitted through farm animals. She called the illness "chronic brucellosis". In that same year, there was an outbreak of a strange illness called "benign myalgic encephalitis", so named because it involved both impairment in brain function and muscle pain.

During the 1970s people equated the fatigue syndrome with hypoglycaemia, or low blood sugar. But, in fact, people with chronic fatigue syndrome do not typically have low blood sugar. Among other suspected causes of chronic fatigue were Candida, a yeast, and the Epstein-Barr virus, a type of herpes virus that causes mononucleosis (or the "kissing disease"). There is no clear-cut evidence, however, that any of these are the primary cause of the syndrome.

Another possible, but still unproven, theory is that severe allergies can trigger chronic fatigue syndrome; some people who believe this theory would rather call the resulting disorder "total allergy syndrome".

About the syndrome

At least two-thirds of the people with chronic fatigue syndrome are women; most are middle-class and white. So there appears to be risk factors among race, sex and socio-economic status that can predispose a person to chronic fatigue syndrome, although we do not understand the reasons for these factors.

Most people with chronic fatigue syndrome relate the onset of the illness to a particular infection, one that they might have had before without such long-lasting consequences. These infections, which at first do not seem severe, most often include respiratory or gastro-intestinal illness, flu-like disease, bronchitis, sore throats, colds or diarrhoea, mononucleosis, hepatitis or jaundice. The vast majority of people recover completely from these illnesses, but a small percentage are left feeling extremely weak, tired and depressed, long after the main symptoms of the infections have vanished. These fatigue-related symptoms can linger. Even so they usually resolve by themselves, but if they persist for more than six months the person may have the chronic fatigue syndrome.

During the early months of fatigue, the patient may feel like he or she is on a medical merry-go-round, going from specialist to specialist in search of what is wrong. An allergist might refer the patient to a neurologist, a neurologist might refer him or her to a psychiatrist. Some patients may benefit from a psychological evaluation and anti-depressant therapy, some do not. And some might be further frustrated by a psychiatrist who determines that the problem is not related to emotional stress or conflict. Right now, established medicine has not provided adequate direction for such patients, who are unsure of where to seek help.

Some patients have formed support groups for chronic fatigue syndrome. These groups (which now exist throughout the United States, Canada, Western Europe and Australia) disseminate information on the illness and provide comfort. People recognise they are not alone in dealing with this still mysterious disease. Other people turn to a more individual approach. Some turn to meditation, acupuncture or acupressure, as well as homeopathic or other non-traditional therapies.

But what can medical science offer, besides an analysis of risk factors for the illness?

So far, investigators are still learning the basic facts. Researchers now recognise that chronic fatigue syndrome could be composed of many elements. One element may be an infection that triggers the initial illness, and could even linger in the body to cause recurring symptoms over long periods. Viruses with this ability include the herpes viruses. This family of viruses contains a protective shell, inside which resides genetic information that allows the infectious agent to persist in the body for life.

Some people with chronic fatigue syndrome do, in fact, have high levels of antibodies to the Epstein-Barr virus, indicating they had experienced a previous infection with it and perhaps recurrent infections as well. But other people with the syndrome have normal or no antibodies to the virus, so that Epstein-Barr virus may not be that important after all. Other evidence that the Epstein-Barr virus is not directly linked to chronic fatigue syndrome comes from studies with a drug called acyclovir, which blocks the virus' multiplication. Patients with chronic fatigue syndrome treated with the drug did not show significant improvement compared to those given a placebo.

Recent studies have suggested that another herpes virus (human herpesvirus type 6) may be playing a role in the chronic fatigue syndrome, but these, and reports linking several other kinds of viruses to the disease, are still preliminary and unconfirmed. So, the search for the infectious agent(s) that may trigger the syndrome continues.

Another common factor in chronic fatigue syndrome is allergy. Patients have twice the number of allergic skin reactions as people without the illness. We do not know why this is so, but this information may indicate that the patients may be overly sensitive to certain agents. Such extra sensitivity may predispose the patients to infections or other types of abnormal reactions to foreign substances and might account for the syndrome.

What do we know about the immune system in people with chronic fatigue syndrome?

Several studies have revealed that certain components of the immune system behave abnormally. For example, chemicals called interleukin-2 and gamma interferon, which the body produces during its battle against cancer and infectious agents, may not be made in normal amounts. Even though these chemicals do not seem to be made normally, there is evidence that a low-grade battle is being waged by the immune system of CFS patients. There is a slight increase in the number of white cells that usually accumulate in the blood when people are fighting off an infection. Natural killer cells, though, that also help the body in this battle are found in slightly reduced numbers. The reduction in natural killer cell activity is very small, and the affected cells comprise just a tiny portion of the immune system. Nevertheless, this subset of cells does tend to have lower activity in people with chronic fatigue syndrome.

It is important to note that another syndrome has the identical, small reduction in natural killer cell activity. That syndrome is clinical depression. Depressed patients have reduced natural killer cell activity and slightly decreased interferon production. In addition, some depressed patients produce higher amounts of antibodies to certain viruses. We do not know why. Therefore, there may be more of a connection between depression, the immune system and the chronic fatigue syndrome than is realised even now.

This brings us to one of the most difficult and controversial aspects of the syndrome, its neuropsychological features. As already described, many of the patients are depressed. But the most common complaint of patients is that they cannot concentrate, whether it is an attempt to get their work done or wash the dishes. They also cannot remember what they have to do to complete a task. Psychologists at the National Institutes of Health and other research institutions are trying to measure such deficits in concentration and memory, and to determine if the impairment can predict risk or help diagnose someone with the syndrome.

In addition to the role that an acute infection may play in triggering chronic fatigue syndrome, many patients report that the onset of the syndrome occurs at a time of great stress, such as a divorce, job change, moving, or a death in the family. These traumatic events seem to predate chronic fatigue syndrome by a matter of weeks or a few months.

What role could stress play in triggering the syndrome?

We do not know the answer to that, but several studies, including some dating back to the 1950s, show a correlation between stress and reduced ability to recover from illness. Other studies show that people under stress may be more susceptible to infection.

In summary, researchers believe that the likelihood of developing chronic fatigue syndrome is enhanced by a combination of factors, including an acute infection and the neuro-psychological makeup of the individual. The syndrome, then, appears to be a problem that requires an inter-disciplinary team of physicians, allergists, psychologists, immunologists and others to tackle. Together, we are searching for the unifying thread that can fully explain and allow us to better treat chronic fatigue syndrome.

In the meantime, physicians can perform tests to rule out other illnesses, many of which require other treatments. And patients can take comfort in knowing that the syndrome they suffer from is not life-threatening, and that most of them will improve with time. The headaches, muscle aches and joint aches can be treated with aspirin, Tylenol or other anti-inflammatory drugs. Adjustments in diet or short-term medication may enable many to sleep through the night. Some individuals may find that anti-depressants enable them to cope with their debilitating illness and feel stronger. In addition to medical treatment, however, both the family and the patient need better guidance about the syndrome. Right now, we do not know exactly what to advise patients. But new research may remove that uncertainty and provide the tools for determining the best way to treat the syndrome and counsel those who are sick.

Questions and answers

Does chronic fatigue syndrome worsen over time?
The pattern of this illness establishes itself very early, although there are some fluctuations. Most people with the syndrome do eventually get better, and we have not seen anyone deteriorate to a more physically devastating, or terminal, illness.

I think I have the syndrome. Where can I go for a definitive diagnosis?

There is no definitive blood test or other diagnostic test. Rheumatologists, immunologists, specialists in infectious diseases, psychologists and allergists all have their own interpretations, but the facts are not all in yet, and we have no objective test.

Do people with the syndrome have heart palpitations or abnormal body temperature?

Some patients do have palpitations. In fact, the syndrome in the 1870s was know as "soldier's heart". But we do not find that the palpitations typically require anti-arrhythmic drugs or other medication. To answer the second part of your question, many people with the syndrome complain of running higher or lower temperatures than normal. As part of our acyclovir study, we took thousands of measurements of body temperature and found no significant abnormalities.

Is shortness of breath a symptom of chronic fatigue syndrome?

Shortness of breath can occur in anyone who is severely de-conditioned and then tries to do even light exercise. But abnormal lung function or low concentration of oxygen in the blood at rest are not a feature of the syndrome.

I have had laboratory tests that indicate I have chronic infection with Epstein-Barr virus. Does this mean I have chronic fatigue syndrome?

No. We have found no definite correlation between Epstein-Barr infection and the syndrome; most people have antibodies to the virus, so the tests are probably irrelevant for diagnosing chronic fatigue syndrome.

Are anti-depressants a treatment for chronic fatigue syndrome?

These drugs may be useful. Some people believe the tricyclic group of anti-depressants is better, while others think monoamine oxidase inhibitor anti-depressants may have more benefit. It is too soon to say which class of anti-depressants is more effective, but this is an area of active study. We are also trying to determine the optimal dose of these drugs for people with the syndrome; some individuals are very sensitive to what may be a moderate or low dose in other patients. And these patients can feel worse if the dose becomes too large.

Can a person's level of natural killer cells be restored if it is abnormally low?

When or how often do recurrent episodes of fatigue or illness occur in someone with chronic fatigue syndrome?

The pattern varies from individual to individual. Some people are ill all the time, some are well except for a single fatigue episode every several weeks. We just cannot predict what will happen.

Is impairment of thyroid activity related to chronic fatigue syndrome?

There are two issues about the thyroid that are relevant here. One is that all patients who undergo evaluation for the syndrome should have a thyroid test, because an over- or under-active thyroid can produce many of the same symptoms, particularly exhaustion. If they have abnormal thyroid activity, we treat them for thyroid disease, and these people respond well to the treatment. Secondly, some patients with chronic fatigue syndrome have antibodies to thyroid proteins, but it is unclear whether that causes thyroid disease. That is a question which is still under study.

I would like to know if meditation or yoga might be an answer for people with chronic fatigue syndrome. I know it helps me when I feel exhausted.

I think anything that reduces stress and makes someone feel more comfortable can help with a lot of illnesses. But I do not know whether meditation is an adequate treatment for this syndrome. The best I can say now is that it cannot hurt, and it may help.