The past few years have brought both profits and perils for those hoping to untangle the mysterious disease of chronic fatigue syndrome.
On the one hand, researchers have made advances in understanding what predispose people to the condition and have identified biological markers (physical changes that can be measured) unique to the disease. Just last month, scientists found a set of proteins in the spinal fluid of chronic fatigue syndrome patients that may distinguish them from healthy people.
But decades after the syndrome was recognized, researchers are still struggling to find its cause. Hopes that a virus was responsible for the disease were put on hold when subsequent tests could not confirm the results. The field remains riddled with problems that hinder progress, including the lack of a stringent definition for the condition. And people continue to stigmatize the syndrome as a disease that is all in mind.
Nevertheless, researchers remain hopeful they can unravel the illness. Even acknowledging that the syndrome is a physical disorder, as many researchers in the United States now do, was a step in the right direction, said Mary Ann Fletcher, a professor of medicine, microbiology, immunology and psychology at the University of Miami Miller School of Medicine.
"I think the whole of field has made enormous strides in coming to the realization that this is an illness that is complex, but it does have biological markers that are associated with it that can be measured and found to be abnormal," Fletcher said. "Using these will help us both diagnose and develop treatments" for chronic fatigue syndrome.
This week, chronic fatigue syndrome experts will meet at a National Institute of Health sponsored workshop in Bethesda, Md., to discuss the current understanding of the disease and how the field can best move forward.
Chronic fatigue syndrome is characterized by extreme fatigue for at least six months that is not alleviated by rest, and cannot be explained by other conditions, according to the Centers for Disease Control and Prevention (CDC). It affects about 1 million to 4 million people in the United States and 17 million worldwide, according to the National Institutes of Health (NIH).
One problem with chronic fatigue syndrome research has been the definition itself. Researchers may use different criteria for including patients in their studies, and as a result, end up with very heterogeneous groups of people, including some that don't even have chronic fatigue syndrome.
"You have to be able to decide who has the illness and who doesn’t have the illness," said Leonard Jason, a professor of psychology at DePaul University in Chicago. "That activity really becomes critical for being able to find out what might be causing the illness, or what might be maintaining the illness or how many people have the illness, or how to treat the illness."
Most researchers use what is known as the Fukuda criteria to define the syndrome. This criteria requires people to experience four out of eight symptoms beyond just fatigue. But Jason says this criteria needs to be revamped, and may need to include additional symptoms, such as feeling tired after exercise, he said.
Additional complications include the fact that patients need to have symptoms for six months before they can be considered to have the condition, making it hard to go back and find the original cause, saidDr. Beth Unger, chief of CDC’s Chronic Viral Diseases Branch. And since patients are often ill for many years, it's hard to distinguish which symptoms are due to the actual disease and which arise as a result of medications (for depression or low blood pressure, for instance) and the burden of being chronically ill, Unger said.
Finding a cause
Researchers are investigating a number of possible causes, including infectious agents (such as viruses), problems with the immune system, genetic factors and exposure to stress.
But experts agree that the syndrome is likely to have more than one cause.
"I think it is unlikely that one specific pathology, or cause, will explain the whole of chronic fatigue syndrome," said Dr. Peter White, professor of psychological medicine at Barts and the London School of Medicine and Dentistry in England. "I don’t think it's going to be totally viral or totally immune or totally psychological … it's going to be a combination."
A 2009 study in the journal Science found an association between chronic fatigue syndrome and the retrovirus XMRV. However, with two exceptions, researchers from other laboratories were unable to confirm these findings. Researchers from Columbia University, the University of Miami and the NIH are hoping to sort out the confusion by collecting blood samples from chronic fatigue patients and healthy people and testing them in three separate labs for XMRV, Fletcher said. The results of this study won't be available for a few months, she said.
Other groups have found patients with chronic fatigue syndrome have low levels of the stress hormone cortisol, Jason said.
There's also evidence that infections, including the Epstein-Barr virus, can trigger the disease.
And chronic fatigue syndrome is associated with other medically unexplained conditions, including irritable bowel syndrome, fibromyalgia and migraines, White said. The field would benefit from having more people who look at the disease in an integrated fashion, rather than at separate components, White said.
"The virologists look for viruses, the immunologists look at the immune system," and psychiatrists and psychologists look at psychological factors, White said. "So everyone looks in their own particular area of expertise, where they feel comfortable, but very few people are putting it together," White said.
As a first step, Fletcher would like to identify a set of biomarkers that would help doctors define patients as having chronic fatigue syndrome. She notes that there are many diseases, including rheumatoid arthritis and diabetes, which can be treated without knowing what exactly causes them. Identifying biomarkers for chronic fatigue syndrome will help researchers develop therapies for patients, even if they don't find the cause first.
"It's clearly possible, if you know what the biological deficits are in the disease, to continue to develop therapies," Fletcher said. "You know that things are wrong, and you have to put them right, and there are ways to do that even if you don’t know exactly why they became to be wrong to begin with."
The time when researchers will have this set of biomarkers is "close at hand," Fletcher said.
If there are several illnesses within chronic fatigue syndrome, several treatments may be needed to treat every patient. It may help to separate patients into groups of people who have similar symptoms and biological changes in order to treat them more effectively, White said.
"I think the future research will include allocating patients to particular subgroups to understand their particular reasons for being ill, and design treatments appropriately," White said.
And if there are multiple causes to chronic fatigue syndrome, multiple therapies may be needed to treat patients. It may help to separate patients into groups with similar symptoms in order to treat them more effectively, White said.
"I think the future research will be breaking patients down into subgroups to understand their particular reason for being ill, and design treatments appropriately," White said.
Pass it on: The past few years have brought advances in our understanding of chronic fatigue syndrome, but a cause has yet to be found. Researchers are investigating biomarkers for the condition to help treat patients.
Follow MyHealthNewsDaily staff writer Rachael Rettner on Twitter @RachaelRettner.
This story was provided by MyHealthNewsDaily, a sister site to LiveScience.
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Rachael is a Live Science contributor, and was a former channel editor and senior writer for Live Science between 2010 and 2022. She has a master's degree in journalism from New York University's Science, Health and Environmental Reporting Program. She also holds a B.S. in molecular biology and an M.S. in biology from the University of California, San Diego. Her work has appeared in Scienceline, The Washington Post and Scientific American.