Chronic Fatigue: A Mystery Unravels
Dr. Jay Goldstein of Anaheim Hills has spent the last five years researching and treating patients with chronic fatigue syndrome, a debilitating disease characterized by incapacitating exhaustion and a range of other perplexing symptoms.
Explaining his theory of an unknown retrovirus invading the immune system, inducing cells to produce a chemical transmitter affecting the entire body, Goldstein pauses. “You know,” the family practitioner says, “some very respected physicians will tell you I am crazy.”
That’s because in posing a medical explanation for the existence of chronic fatigue syndrome--a disease with no known cause or cure--Goldstein is bucking conventional wisdom. For years now, many in the medical community have regarded the ailment as primarily psychological, and they are wary of practitioners who pose unproven medical theories.
But, in fact, a growing number of the nation’s most respected scientists are taking the illness very seriously, researching various hunches and theories of their own, as they reported at the First Chronic Fatigue Syndrome Conference held last weekend in San Francisco.
Dubbed ‘Yuppie Flu’
Once dubbed the “yuppie flu” and dismissed as a vogue ailment affecting neurotic women, chronic fatigue syndrome is now believed to be a complex illness of immune dysfunction that affects people of both sexes and varying ages and ethnicity.
Though there is little funding for its study, scientists are hoping to understand more about chronic fatigue by scrutinizing viruses, including the involvement of the newly discovered Human Herpes Virus 6, or HHV-6, which has been linked to cancer and AIDS; questioning whether chronic fatigue is linked to multiple sclerosis; puzzling over how it is transmitted, and experimenting with treatment.
“Even AIDS was simpler than this, because it was caused by one virus, and that virus is very new in the last 20 years. It is more likely (with chronic fatigue) that a whole bunch of other old viruses and other infectious agents are all able to cause some people’s bodies to act in a particular way to cause this disease,” said Dr. Anthony L. Komaroff, associate professor of medicine at Harvard University and chief of general medicine at Brigham and Women’s Hospital in Boston. “It is only since new technology has enabled us to take pictures of what goes on in the brain that many physicians became convinced this was an illness,” he said.
Komaroff, a presenter at Saturday’s conference attended by about 500 health-care professionals, said he and other researchers speculate toxins, heredity, allergy and stress may work in concert with other factors to trigger the malady.
Although statistics documenting its prevalence aren’t available, chronic fatigue syndrome has been classified as a disease by the U.S. Centers for Disease Control in Atlanta, which is launching a four-year study. In evaluating a grant proposal, the CDC recently noted the illness “appears to be reaching epidemic proportions.”
Nationwide, there are more than 200 support groups for patients. The CFIDS Chronicle, the journal of the nonprofit Chronic Fatigue and Immune Dysfunction Syndrome Assn., based in Charlotte, N.C., publishes a bimonthly, 70-page journal of advocacy information and research.
Repeatedly, chronic fatigue sufferers talk of callous treatment by the medical community. Through the course of her two-year illness, conference speaker Melinda Paras, 35, of San Francisco, said she dealt with seven practitioners at her health maintenance organization. On one occasion, she said, she was told: “ ‘This is a seven-minute appointment. I don’t have time to hear your complaints.’ ”
After a battery of laboratory work, Paras was advised to take an AIDS test. As terrible as it was to wait two agonizing weeks for the appointment and another two weeks for results, it paled by what was to come, she said. “Absolutely the worst part of this disease came when I had a particularly acute attack and was so weak I couldn’t breathe and could hardly move. I was scared. I called the HMO, and the nurse-practitioner said: ‘There is nothing more we can do for you. We recommend you seek psychiatric treatment,’ ” Paras recalled.
Formerly a program coordinator for a nonprofit institution, Paras was stricken while on a business trip in Washington. She thought it was severe flu, but in the next two months became so debilitated, “it took me 30 minutes to crawl to the bathroom and I had to take a nap on the floor for 30 minutes on the way back to bed.”
Another speaker, Tom Hennessey, a 35-year-old former BMW salesman who described himself as “a very aggressive, competitive person,” said he is now unable to work because of chronic fatigue and has spent his last $20,000 on medical expenses. “My life savings and individual retirement account are gone,” Hennessey said, “and I have sold two cars. I don’t have the money to pay the May rent.”
Recently, his claim for Social Security disability was denied, he said. He urged health-care workers assembled to support patients with letters and documents necessary for disability payments, rent subsidies and food stamps. “We also need buddy systems to help us with chores, such as cooking, cleaning and taking care of ourselves,” he added.
Many are struck in theirs 30s and 40s, experts say, more often women than men. Typically, incapacitating exhaustion is accompanied by flu-like symptoms, including sore throat, swollen lymph glands, drenching night sweats, chronic cough, painful and weak muscles and joints, and dizziness.
Some also exhibit multiple sclerosis-like symptoms, such as disorientation, memory loss, inability to concentrate, balance disturbances and brain inflammation. The disease can last for six months or two years. Others never seem to recover.
There is disagreement on how long chronic fatigue syndrome has been around, perhaps in different guises. Estimates range from the last 30 years to more than 120. In the 20th Century, it has been identified as anemia, a bacterial infection, low-blood sugar, environmental allergy, bodywide yeast infection, and more recently, Epstein-Barr virus syndrome, which causes infectious mononucleosis and other diseases.
However, Dr. Paul Cheney of the Nalle Clinic in Charlotte, N.C., speculates chronic fatigue may be an old disease that has evolved. “If this had been around for 200 years, with people this sick, I can’t believe we could have missed it for so long,” he said. “I think it’s something that has existed as long as viruses, but some new co-factor has been added, as well.”
In searching for clues, scientists are trying to understand how viruses work singly and together as well as how they affect the immune system.
Although HHV-6 and the Epstein-Barr virus don’t cause chronic fatigue syndrome, they may hold powerful clues, researchers say.
Evidence of Virus
“We now have evidence that HHV-6 is present and active at the time (chronic fatigue patients) are sick,” Komaroff reported, citing a collaborative effort with Dr. Dharam Ablashi of the National Cancer Institute and Dr. Berch Henry of the University of Nevada. The finding may be significant, Komaroff said, because an active virus can infect cells of the nervous system, which might contribute to some or all symptoms of chronic fatigue syndrome. At the National Cancer Institute in Bethesda, Md., a high prevalence of antibodies to HHV-6 also has been found in patients with Burkitt’s lymphoma, non-Hodgkin’s lymphoma and childhood acute leukemia.
Researchers hypothesize that, like the AIDS virus, HHV-6 has the ability to kill the immune system’s helper cells. “In the culture system, we have found that when you can co-infect these CD4 helper-positive cells with two viruses, the cellular killing effect is much faster than either will do alone,” said Ablashi, coordinator for DNA virus studies at the National Cancer Institute. In a similar vein, investigators speculate that the combination of Epstein-Barr and HHV-6 might co-infect the immune system of chronic fatigue patients in a devastating manner.
Still a Puzzle
Just what goes on their immune systems is a puzzle. “It is very difficult to sort out the mix of what different agents may be causing this illness. The only common denominator for all potential causes or co-factors seems to be the element of immunological dysfunction in all these patients,” Cheney of the Nalle clinic said.
Cheney became interested in the disease while practicing medicine in the early 1980s. At the time, he was inundated with patients from Lake Tahoe suffering from what he thought might be a chronic mononucleosis-type illness.
After years of research, he believes “the immunologic problem isn’t necessarily a severe one like AIDS. It looks as much like an allergy. Rather than being suppressed, the immune system looks like it is hyper-responsive, really fighting something.” Theoretically, he added, the immune system’s raging battle may be one reason chronic fatigue patients feel ill constantly.
Virologist Dr. Jay Levy and his Chronic Fatigue Syndrome Research Group at UC San Francisco have been unsuccessful in attempts to isolate an agent that might cause chronic fatigue. Perplexed by patients whose symptoms resemble multiple sclerosis, he poses these unanswered questions: “Are these really MS patients, or is this an early sign of multiple sclerosis in some people? Could chronic fatigue syndrome be an acute symptom of another virus that gives rise to multiple sclerosis in certain people?”
Another researcher, Dr. David Bell of Lyndonville, N.Y., started seeing children with what he now believes is chronic fatigue syndrome in 1983. “These children had large lymph nodes, big spleens and were quite sick. They still are sick today,” he said.
Genetic or Infectious?
After identifying 21 cases at a local school, the pediatrician compared the youngsters with a group of 42 healthy children, examining about 50 factors. Among his findings: “The people who got sick had a high rate of allergy, implying a genetic marker. There was a high rate of people within the same family becoming ill, implying an infectious agent. And people with the illness were much more likely to have been drinking raw milk.” After three years of research, however, the pediatrician has been unable to explain what role raw milk might play.
Bell, who is affiliated with the Roswell Park Memorial Institute, a cancer research center in Buffalo, N.Y., reflects a common complaint about lack of research grants. “When you see a disease that is so devastating to the lives of children and families, it is remarkable that so little has been done about this. I see children who haven’t been out of bed in a year, and yet there is very little government response,” he said.
Also of concern to doctors is the impact the illness appears to have on the brain. Cheney said brain tests in some patients reveal unexplained white lesions of the cortex--the brain’s outer layer of gray matter--and abnormalities in the temporal lobes where vision, hearing, memory and emotion are processed.
“Our scans, mapping electrical activity, show there are characteristics of brain lesions in almost all of the people who have chronic fatigue syndrome,” added Goldstein of Anaheim Hills. “In some patients, we see areas of decreased blood flow in certain areas of the brain.”
These changes correspond with cognitive impairment. “I have seen IQ tests drop 30 points. I have a doctor in my practice who can’t drive a car because he can’t read street signs and mothers who don’t remember the names of their daughters,” he said.
He theorizes that an unknown virus enters cells of the immune system of a genetically susceptible person, inducing production of a chemical transmitter or cytokine. Other cells, in turn, make their own transmitter chemicals. “You can almost view the immune system and the brain as one organ. The body is a network of these communicating systems,” Goldstein said.
He speculates that by treating the brain, the immune system can be altered. Experimenting with a drug that increases slow-wave sleep, he plans to study “in what ways this treatment might make people feel better.”
Other clinicians are also searching for treatments. In some of her patients, Bay Area physician Dr. Carol Jessop has found an imbalance of gastrointestinal bacteria and yeast caused, she believes, by chronic use of antibiotics, a high-sugar diet, birth control pills, steroids, or, in some people, an immunosuppression caused by an unknown viral agent.
Meanwhile, patient advocacy groups are becoming increasingly vocal. Jan Montgomery of San Francisco’s Chronic Fatigue Immune Deficiency Syndrome Foundation was instrumental in urging city officials to form a task force resulting in the conference, co-sponsored by the San Francisco Medical Society, the San Francisco Department of Public Health and the UC San Francisco Department of Medicine and School of Nursing.
And researchers, too, are coming to the defense of chronic fatigue patients.
“I don’t believe, personally, these are people who are primarily depressed or psychologically ill,” said Dr. Leonard S. Zegans, professor of psychiatry and director of professional education at the Langley Porter Institute, a UC psychiatric research, teaching and treatment facility.
The disease represents powerful stress, the psychiatrist said. Moreover, symptoms such as impaired attention and anxiety alter performance at work or school, “calling self-worth and self-esteem into question.” Not being able to work is especially devastating because “many of these people are ambitious,” Zegans added. Patients become isolated, in part, because “not everyone believes they are sick.”
He, too, suspects a virus, latent in the blood stream, maybe re-activated by a variety of causes, including stress.
“We are just now beginning to learn about the interaction between the nervous system and the immune system,” he told his colleagues at the conference. “We have a very complex system of checks and balances in the body and there perhaps are ways in which the equilibrium of body defenses can be altered. I think in the next 20 years, we are going to be learning a tremendous amount about this.”
For more information about chronic fatigue syndrome, contact the CFIDS Assn., P.O. Box 220398, Charlotte, N.C. 28222-0398, or call (704) 362-2343.
SYMPTOMS OF CHRONIC FATIGUE SYNDROME Debilitating and persistent fatigue in someone without a history of fatigue. Activities are severely curtailed for at least six months. Eight of these 11 indications: sore throat; mild fever or chills; painful lymph nodes; muscle pain; muscle weakness; prolonged fatigue after exercise that is normally easily tolerated; headache different in type or severity from past headaches; joint pain; sleep disturbances; neuropsychological complaints such as excessive irritability, forgetfulness, confusion, depression, difficulty thinking or concentrating; visual disturbances and light phobia. Symptoms are said to develop over a few hours or days. Or, six of the 11 symptoms above and two of the following three physical signs, documented by a physician on at least two occasions at least one month apart: low-grade fever, inflamed throat and enlarged nodes in the neck or armpits. SOURCE: U.S. Centers for Disease Control.