Articles / Essays

Chronic Fatigue Syndrome: From Skepticism to Science

by Dorothy Wall
from San Francisco Chronicle Magazine

After 20 years, chronic fatigue syndrome may finally be getting some respect and cutting-edge science.

It was 1984 when Dr. Carol Jessop, then an associate professor in the Department of Internal Medicine at UCSF, first saw the patient she would never forget. A 40-year-old business woman who had always been healthy and active came to the clinic with a bizarre story. While driving on the freeway, she was suddenly hit by such overwhelming nausea and fatigue she had to pull over. "It was dramatic," remembers Jessop. "I'd never heard anything like this before, that sudden. This woman absolutely felt drained and near collapse."

The mystery quickly deepened. Jessop drew some endocrine labs, checked the woman's cortisol level, looked at her CBC (complete blood count), and "low and behold, everything comes back totally normal. And she's getting worse by the time I see her in follow up. Now she's aching all over, has some baseline headaches, she's not sleeping well, and she just feels like she's caught in a flu."

Concerned, Jessop consulted with a colleague in infectious disease at the university, and talked with another in endocrinology. Within the month, a couple more patients had come in with similar stories of overwhelming malaise and fatigue, muscle aches, confusion and concentration problems.

"A lot of my colleagues said that these people must just be depressed. Put them on tricyclic anti-depressants," reports Jessop. "I definitely felt that there was some criticism of my work and my attempt to try and uncover what was going on."

But Jessop persisted. "I was clear in my head something was happening, and I was willing to look in every direction." By 1986, she was seeing more than 300 patients with the now-familiar symptoms, and cluster outbreaks had been reported in cities and towns across the country, including a well-publicized one at Lake Tahoe. She consulted with UCSF virologist Jay Levy who was then working to discover the HIV virus. She and Levy wondered whether they were seeing a new virus or something related to AIDS in a milder form. Somehow, they felt, the immune system in these patients had been disrupted.

When we get sick with a flu, the fever, achiness and fatigue are not caused by the virus itself but by the immune response, the chemicals released to fight infection. Perhaps Jessop's patients had an immune system stuck in the "on" position, creating persistent flulike symptoms. But what virus was causing the disruption? After investigating a number of potential culprits—human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), among others—Jessop and Levy, like other investigators, came up empty.

In 1988, the Centers for Disease Control and Prevention (CDC) named the puzzling illness chronic fatigue syndrome (CFS), as if this illness were about nothing more than being a little extra tired. The moment the name was set in print, patients lambasted it for trivializing a devastating illness and inviting psychiatric stigma. By 1991, Jessop was seeing some 1,500 patients with CFS, marking the Bay Area as one of the largest clusters of the nationwide epidemic. Most of these patients had been ill for years—some bed- or housebound—and many were unable to work. Yet without a known cause or laboratory evidence of abnormalities, the illness continued to be subject to psychiatric explanations by physicians, disbelief by family and friends of those who were ill and media ridicule as the "yuppie flu."

 

It has been a long journey from those early days when only a few renegade physicians like Jessop took this illness seriously. After two decades of dogged advocacy work by patients and a handful of concerned physicians and researchers, the facts about CFS are coming to light. Today CFS—also called chronic fatigue and immune dysfunction syndrome (CFIDS) and myalgic encephalomyelitis (ME)—is known to be a serious and disabling illness affecting an estimated 800,000 adults in the United States, although it appears that only 10 to 17 percent of these cases have been diagnosed. Studies by the CDC show that people with CFS can be as impaired as someone with heart disease, cancer or multiple sclerosis and that CFS costs the economy $9.1 billion a year in lost productivity. Two to five times as many women as men have the illness, and contrary to popular myth, minorities and people at lower socioeconomic levels are at higher risk for CFS.

Most medical textbooks now have a section on CFS, and though the great majority of physicians say they feel inadequately informed about the illness, many want to know how they can help their patients. Jessop reflects on the change. "I think today, physicians have studied fibromyalgia, have studied CFS, and many of them are more comfortable saying, `OK, we don't know everything about it, but let's talk about what we can do.'"

While the cause is still unknown, the search for a single virus no longer occupies most researchers. Most now suspect CFS has a variety of triggers, alone or in some combination: one or more pathogens, chemical and environmental exposures, stress or injury and genetic predisposition. Whatever the initial provocation, the autonomic, immune and neuroendocrine systems become dysregulated, producing the constellation of symptoms: overwhelming fatigue, postexertional malaise, muscle and joint pain, sore throat, swollen lymph glands, light and sound sensitivity, headaches, "brain fog" and cognitive problems.

Like Jessop, pediatrician David Bell saw a cluster of patients with what looked like a severe viral illness in his clinic in Lyndonville, N.Y., in 1985. He and his wife Karen, an infectious disease specialist, at first considered everything from typhus to Rocky Mountain spotted fever to Q fever. They, too, suspected an infectious origin, but couldn't find a specific bug. And they, too, encountered disbelief from other specialists they consulted. Says Bell, "The specialists wrote back and said that these kids are all neurotic and they're just exaggerating the symptoms, which I knew couldn't possibly be true." After treating and studying CFS for 20 years, Bell has a clearer picture.

"I see this illness as a post-infectious dysautonomia [autonomic nervous system dysfunction]....What that means is that an infection initiates a process whereby the immune system starts overreacting. And that process then causes reduction in cerebral blood flow, abnormalities in the HPA axis [a key part of the endocrine system] and a variety of other things."

Bell's description of a possible disease process in CFS reveals the complexity of this illness: an immune system that is overreacting, reduced blood flow to the brain, defects in the autonomic system that controls heart beat and blood pressure, abnormalities in the endocrine system regulating production of hormones. Multiple things are going wrong in the body of a person with CFS, one affecting another in a cascade of interactions. Adding to the complexity, the disease process may not be the same in all people with CFS. Just as a painful, swollen joint can be caused by infection, injury or arthritis, the symptoms of CFS may be the end result of different processes. Researchers are recognizing the importance of subtyping patients—perhaps by similar symptoms or illness history, or by the predominant organ systems involved—to make both treatment and research more effective.

 

One of the biggest obstacles to understanding CFS has been the absence of a "big picture" view, and this absence is directly tied to lack of federal research money. Until recently, most CFS studies have been small, often funded by patient advocacy groups, and narrowly focused. One study of 36 subjects might document difficulty with multi-tasking; another study of 121 people with CFS shows they have low levels of the hormone cortisol.

Like many, Bell is angered by the lack of federal investment in research. "The amount of money being spent on research is trivial. I mean, it's so small that it just doesn't count when you compare it to other illnesses affecting huge numbers like this is." According to its own documents, the National Institutes of Health (NIH) in 2003 spent $99 million on multiple sclerosis and $6 million on CFS, though CFS affects twice as many people. Bell adds, "And a lot of that $6 million was spent on fatigue independent from chronic fatigue syndrome." Adding insult to injury, documents released under a Freedom of Information Act request made by CFS advocates revealed that between 1995 and 1998, the CDC spent $12.9 million allocated for CFS on other projects, and misrepresented its spending to Congress.

Under intense pressure from patient advocates, particularly the CFIDS Association of America, the largest patient advocacy group, the CDC restored the misallocated funds, mostly in fiscal years 2002 and 2003, and finally started a major research effort. Federal funding for CFS research—from both the NIH and the CDC—was still only $16 million in 2003, according to the CFIDS Association, and today is on the decline. Nonetheless, the current federal undertaking is significant. The CDC's main goals are to understand whether CFS is one disease or many, to define its natural history and clinical presentation, to educate health care providers and to identify the pathophysiology (disease process), causal agents and risk factors.

There's been quite a buzz about several studies under way. Bell's voice rises with enthusiasm when he describes them. "One was the Dubbo study by the CDC. Extraordinary study. Wonderful science. What they're doing is, in the county of Dubbo, Australia, they're prospectively looking at all cases of Epstein-Barr virus, Ross River virus and Q fever, illnesses known to sometimes have a chronic aftermath. And they are now seeing that 10 percent of these people go on to develop chronic fatigue syndrome....This is implying that those three infections cause CFS in otherwise healthy people. That's very interesting.

"The other study...that just knocked my socks off was hepatitis C. This was a study done by a hepatitis specialist who was treating hepatitis C with interferon," a protein that is part of the body's anti-viral response...."Seventy percent developed marked fatigue, and 30 percent developed chronic fatigue syndrome. So it was the interferon treatment that caused the CFS, not the actual virus circulating in their system....The CFS is the immune response from an infection." This finding is consistent with the idea that the symptoms of CFS could be precipitated by an immune system in overdrive.

 

A key component of the CDC research effort is the use of microarray technology to analyze the genetic material of a person with CFS. Researchers take a sample of blood or tissue; apply it to a glass slide, called a "microarray," which contains more than 20,000 gene identifiers; and are able to determine which genes in the sample are being "expressed," that is, turned on or off, or turned up or down. This gene expression profile provides a window into the disease process.

Microbiologist Suzanne Vernon, team leader of the CDC's molecular epidemiology program, explains: "We're using very exploratory molecular technologies to try to understand what is wrong in people with CFS. We've tried to focus on discovering biomarkers that help us to further understand the pathophysiology of CFS and also to perhaps identify diagnostic markers." Since 1988, CFS has been diagnosed based on a patient's symptoms and by ruling out other illnesses that can cause chronic fatigue. Finding a diagnostic marker, a measurable biological abnormality that appears in all people with CFS, would be an important step forward.

In preliminary work, Vernon's team has been able to use microarray technology to distinguish between people with CFS and healthy controls. More recently, they've been able to show differences among people with CFS, confirming that CFS is a heterogeneous illness. Examining 3,800 genes in 23 women, they found that those with sudden-onset illness (developing in one week) had a different gene expression profile than those with gradual onset (developing over several months). With further study, researchers hope to find a common pattern or signature of gene expression that appears in all people with CFS. They may find particular patterns that are specific to subgroups as well. Eventually, the microarray could become a routine diagnostic tool for CFS.

Even more ambitious is the team's effort to integrate this gene expression data with epidemiologic (age, race, sex) and laboratory (blood work, urinalysis) information. "We just recently finished all of the gene expression profiling on a study that was conducted in Wichita, Kan., a two-day clinical study of 250 subjects," Vernon says. "We were able to profile 20,000 genes from 177 subjects, and we are in the process of looking at those gene expression profiles."

These Wichita subjects, including people with CFS and healthy people, also underwent a battery of neuroendocrine and immune studies, sleep studies, and tests for cognitive function. "It's actually a very rich and incredibly complex data set," Vernon says. "It's not just two things that we're trying to put together, it's multiple things. For instance your physical symptoms—quantifying fatigue, levels of cognitive impairment, sleep problems—with other laboratory measurements, in addition to gene expression measurements."

Vernon has assembled four teams of six investigators—from disciplines including medicine, molecular biology, mathematics, physics and computer science—to tackle the Wichita clinical data set to try to further the understanding of CFS pathophysiology. "Our group is one of the few multidisciplinary groups there is that's studying CFS....I think our group is realizing that it is going to be the way to cure CFS....Because of the complexity of this illness, you have to have many different perspectives."

How close are we to that diagnostic marker? Vernon pauses. "I hope we're close, is what I would like to say." She laughs. "I don't want to give a date because everybody in my lab will panic."

Finding effective treatment for CFS is another long-term goal. "Isn't that the dream of any scientist?" Vernon says. With a better understanding of the disease process, specific, therapeutic interventions may one day be possible. But for now, treatment for CFS is limited to managing symptoms, such as pain or sleep problems. However, symptomatic treatments don't address the underlying disease, which, Vernon says, "could end up affecting people for the rest of their lives."

What happened to the woman Jessop first saw in her clinic in 1984? "I ran into her about a year ago," says Jessop, who is now a hospital-based internist in the East Bay and no longer sees CFS patients. "She never enjoyed the life that she had before, but I think she was much better. Certainly she was out of bed and doing things." Like this woman, the majority of people with CFS gradually improve, but only an estimated 10 percent enjoy full recovery. Many stay the same, and some worsen with time. Questions about who will recover and when remain unanswered.

***

Originally published in the San Francisco Chronicle Magazine, June 5, 2005
Copyright © 2005, Dorothy Wall. All rights reserved.

***

More on ME/CFS by Dorothy Wall: Encounters with the Invisible: Unseen Illness, Controversy, and Chronic Fatigue Syndrome is available to buy now online or call toll-free 1-800-826-8911.

***

 

Facing

by Dorothy Wall
from Breaking Free: Women of Spirit at Midlife and Beyond

On an Oprah show about weddings, a celebrity appeared with her daughter to regale viewers with the extravagant details of her daughter's wedding: gold-embroidered napkins; jewel-strung dress; dense, velvet stands of roses and tulips as if out of a Renaissance oil-painting. I found myself watching like the outsider we all are to celebrity lives, fascinated and appalled. (Over three million dollars for a wedding when the fourth graders my daughter teaches are virtually without books!)

As mother, daughter and Oprah gushed, I was struck by the celebrity's face. Sitting next to her daughter, who looked like a regular person, this woman looked not like a mother but a caricature of her younger self, her skin so face-lift taut as to be masklike, eyes weighted with mascara, blond pageboy that fit like a helmet. She made me think of a Marcel Marceau mime routine in which a man is stuck in a laughing mask. He makes a great effort to pull it off, heaving and staggering around the stage, but can't dislodge it. The audience laughs at his antics, seeing only his laughing face, while underneath the mask the man is crying. No one can see his pain. He is caught in his solitude, alone with what he feels, unrecognized.

This woman's face had become that mask, a smiling reproduction of youth, divorced from the self inside. It made me sad, evoking echoes of Dickens's Miss Havisham sitting for decades in her moldering wedding dress, waiting for her groom who never arrives. Unable to arrest the moment of youthful ardor and anticipation, Miss Havisham arrests only the props around her, and even they decay until she is jilted by time as much as by love. For all its careful preservation, this celebrity's face, like that yellowed wedding dress, was a costume that with each passing year would be less matched to the person inside.

Those who have face-lifts may think they have preserved their face. In fact, they have been defaced, the marks of a life removed, the blemishes, the idiosyncracies. We think of defacing as spoiling what was originally pristine, perfect. This defacing is the opposite: it attempts to restore perfection by stripping a face of what is personal, singular. To be defaced is to lose part of the self, our individual expression.

The promise of the reconstructed face is not just that it will be eternally young or perfect, but that it is reproducible. If it can be made for celebrities it can be made for others, the same high cheekbones, taut skin. We can mold a face, make it as art object, manipulate it, change it. We can do it for you. The face has become a consumer product, an exchangeable commodity. It can be both discarded and acquired, an emblem of commerce and exchange. Familiar terrain for women. To reclaim our natural face is to step out of this commercial landscape.

After the Oprah show I was compelled to dig up and pin above my desk an old postcard/photo of artist Georgia O'Keeffe, standing in the desert like a tree. O'Keeffe's face is turned away from the camera, unconcerned with the viewer. She gazes into the distance as if focused on an inner vision and the grandeur of the desert around her at the same time. Her face is lined, stolid, implacable, like photos of Indian warriors. There is no artifice, no cover, no disjunction between face and self. She is not smiling, neither does she appear sad. She radiates strength and self-possession, a word she embodies: to literally possess the self, to not be apart from who you are.

If the cover-up of the aging face, as Jungian psychologist James Hillman and others contend, acts to discourage the revelation of character, then a face left bare is a revealing marker of a life. It is precisely this exposure that produces the urge to disguise. What if our face shows sadness, strain, fatigue--or worse, our own fragility and decay, no longer a perfect surface. So what, O'Keeffe says. This is the whole of who I am.

In a remarkable statement about the trap of perfection, actress Heddy Lamarr lamented in her 1966 autobiography Ecstacy and Me, "My face has been my misfortune....My face is a mask I cannot remove. I must always live with it. I curse it." A woman of intelligence and humor, she felt confined by a public perception that equated her self with her beautiful face. How ironic and sad that other women work hard to reproduce that confinement.

To don the mask of perfection reinforces a narrow definition of beauty and acceptability that will heighten not dissipate our anxieties about age. The artificial and ultimately futile attempt to stop our natural progression into age is an act of self-abandonment. We become like both Marceau's audience, who can't see, and the man behind the laughing mask, who is trapped: we're unable to see how we're trapped in our own effort.

To face: to meet or confront squarely. To confront with boldness, courage. Facing: to turn the face in a specified direction. Like many people, I track my loss of youth with the eyes of the amazed inner self struggling to adjust. But I hope I'll have the courage to face my aging with curiosity, amusement, pride, and equanimity, and to confront boldly or turn away from the viewer's gaze. Like O'Keeffe, I want to draw my gaze from within and focus it outward on the astounding world around me.

***

Originally published in Witness, Vol. XVI, No. 2, 2002, Special Issue, Aging in America. Reprinted in Breaking Free: Women of Spirit at Midlife and Beyond, edited by Marilyn Sewell, Beacon Press, 2004.

 

↑ top