|HEALTH | summer 2006
Hopeful new research shows that chronic fatigue syndrome may have a genetic basis.
Until recently, the prognosis for a patient diagnosed with chronic fatigue syndrome (CFS) was bleak. The illness has no recognized cure, let alone specific tests to diagnose it—just a bewildering set of symptoms, including utter exhaustion and debilitating pain in joints and muscles. Without a clear medical explanation, patients also face a confused response from family and friends: Is CFS nothing more than over-the-top ennui? A fancy synonym for hypochondria? Even the term “chronic fatigue” diminishes the disease, conjuring an image of Madeline Kahn’s classic rendition of “I’m Tired” in Blazing Saddles.
But medical research has now made some major advances in understanding the syndrome, underscored by what may be a breakthrough study by the Centers for Disease Control and revention (CDC). The CDC looked at the genetic code of 227 CFS patients and controls in Kansas and found differences in the genes of the CFS patients involved with immune system, brain and endocrine regulation. Some of their findings suggest that the disease might be caused by genetic mutations that impair the central nervous system’s ability to adapt to stressful situations.
The study revealed at least three distinct forms of the disease, each presenting a different genetic profile, one of which seemed to be associated with menopause. In addition, researchers found a strong correlation between the severity of CFS and what is termed allostatic load—the cumulative wear and tear on the body resulting from chronic or inadequate adaptation to stressors such as changes in everyday routine, disease, and physical and emotional trauma. The CDC is now preparing to replicate the findings in a study involving 30,000 people in Georgia.
This is a huge step forward in terms of diagnosing and hopefully treating CFS—and that’s especially encouraging news for women, who are three to five times more likely to suffer from the disease than men. The fact that it skews so heavily toward women has also caused some to dismiss CFS as a “woman thing”— the modern version of a fainting couch for the frail sex. This sort of pejorative labeling is nothing new: The term hysteria is, after all, derived from the Greek for womb. Once a disease or affliction is perceived through the “gender lens,” the credibility of the illness may be questioned, causing severe negative impact on research funding, and thus limiting options for treatment.
CFS has been misunderstood and mislabeled since the first case definition in 1988. Initially, it was frequently called “yuppie flu,” as it is sometimes marked at onset by severe flu-like symptoms (in other cases, however, there is a gradual decline with no dramatic onset). But CFS hardly follows a yuppie demographic: It’s found most commonly among those ages 40 to 69 and in lower-income groups, although it crosses borders of country, ethnicity and class.
Only an estimated 16 percent of adult CFS patients have actually been diagnosed with the disease, and with no reliable diagnostic test or biologic marker the symptoms are sometimes mistaken for depression. In depression, however, one of the markers is an enlarged adrenal gland and an increase in cortisol production, while in CFS the adrenal gland is smaller than normal and makes less cortisol. This and other findings have shown that depression cannot explain the symptoms of CFS, yet many doctors still treat CFS patients with antidepressants—then regard them as recalcitrant when the treatment does not work.
Attracting researchers and research dollars to investigate CFS has been a catch-22 scenario: It’s difficult to raise research funding for an illness that is so misunderstood, yet lack of adequate funding has limited the kinds of studies that might yield definitive answers. Clinical trials are needed to understand the various subgroups of CFS and to discover treatments that address the true biologic underpinnings of this illness. We also must educate healthcare professionals so that every doctor, nurse practitioner and physician assistant can quote the diagnostic criteria and treatment strategies.
Fortunately, some of the research issues are finally being addressed. Sensing that investigators were discouraged by a 50 percent drop in CFS research funding since 2003, the NIH Office of Research on Women’s Health, under the leadership of Vivian Pinn, put up $4 million for a special round of NIH applications last fall, resulting in 36 applications and likely funding for eight. This compares with a typical four or five applications per quarterly round, and only four to six funded studies each year.
More good news: In 2005, the combined efforts of a group of CFS advocates led the Nevada Legislature to pass a bill funding a state-of-the-art Center for Excellence for CFS and cancer. Opening in 2007 or 2008 at the University of Nevada-Reno, the center will include a $75 million research and clinical-care facility.
People often ask me if CFS is an immune disorder, a brain disease or a malfunction of the endocrine system. I tell them it is all of these. How I view the disease today, however, is not the way I once perceived it. As an immunologist, I once would have said that CFS is clearly an immune dysfunction state, while an endocrinologist would call attention to the adrenal gland irregularities, and a specialist in the autonomic nervous system would be convinced CFS is all about blood pressure.
It is not uncommon, however, for a disease to be misunderstood—even by medical professionals—when there is no reliable diagnostic test. Multiple sclerosis, for example, was once called hysterical paralysis, and doctors treated patients like hypochondriacs and assumed they couldn’t cope with life. Then, with the advent of new technology (in this case MRI), scientists and clinicians were able to see brain lesions in MS patients and skepticism vanished.
In spite of the many obstacles that have constrained research to date, we have learned an enormous amount about chronic fatigue syndrome since it was first recognized. The ignorance and prejudice that once blocked a CFS patient’s hope for a return to normalcy is being chipped away, and some day soon the puzzle of this complicated illness may be solved.
For further information on CFS, visit the CDC, NIH, International Association for Chronic Fatigue Syndrome, or CFIDS Association of America.
Nancy G. Klimas, M.D. is one of the
nation’s foremost experts on CFS. She is
a professor of medicine, psychology, microbiology
and immunology at the University
of Miami School of Medicine,
and president of the International Association
for Chronic Fatigue Syndrome.