Chronic fatigue syndrome (CFS) is a controversial diagnosis that has also been called myalgic encephalomyelitis (ME or ME/CFS), post-viral fatigue syndrome (PVS), chronic fatigue immune dysfunction syndrome (CFIDS), Iceland disease, “yuppie flu,” and many other names. A new report from the Institute of Medicine (IOM) says that none of those names really fit the disease and recommends it be re-named systemic exertion intolerance disease or SEID.
ME/CFS is thought to affect as many as 2.5 million Americans. The cause remains unknown, but in many cases it appears to have been “triggered by an infection or other prodromal event, such as immunization, anesthetics, physical trauma, exposure to environmental pollutants, chemicals and heavy meals, and rarely blood transfusions.” Some doctors question its very existence and interpret the symptoms as imaginary or psychological.
The IOM examines the evidence base
At the request of several government agencies including the NIH and the FDA, the IOM convened a committee of 15 experts to examine the evidence base for ME/CFS. They reviewed over 9,000 published studies and heard testimony from patients and advocates. Before publication, an additional 15 experts were asked to provide peer review. The full text of the report is available free online.
Few people will want to read the entire 304 pages, but dipping into it will give you a sense of the complexities of the issues, the rigor of their investigation, and the judgment that went into their recommendations. The section on history is particularly worthwhile.
They concluded that there was good evidence that ME/CFS is a real entity:
ME/CFS is a serious, chronic, complex, multisystem disease that frequently and dramatically limits the activities of affected patients.
They consolidated the published evidence to determine which symptoms were most representative of the disease, and they proposed new diagnostic criteria based on the best available evidence.
Problems with diagnosis
When CFS was first recognized as a new entity, it was thought to be associated with Epstein-Barr virus (EBV) and was called chronic EBV syndrome. When the relationship with the virus didn’t hold up, it was re-named chronic fatigue syndrome and a working definition was established for the purposes of research. That working definition was not originally intended for clinicians to use in diagnosing individual patients, but it was quickly adopted for that purpose without any formal validation.
Diagnosis has always been problematic: more than 70% of patients reported seeing four or more doctors before receiving a diagnosis. There have been at least 20 sets of diagnostic criteria or case definitions. One of the most commonly used is the Fukuda case definition, which requires prolonged fatigue that persists or relapses for 6 months or more, plus four or more of the following: impaired memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle pain, multi-joint pain, new headaches, unrefreshing sleep, and post-exertion malaise.
The problem with these definitions is readily apparent. Most of the criteria are subjective and not easily quantified. How much fatigue? How do you distinguish between physical fatigue and psychological fatigue? How much impairment of concentration? Everyone experiences fatigue and memory lapses; when does it become pathological? Even tenderness of lymph nodes relies on subjective patient reports and depends on how hard you press on them. Individuals with major depression, hypochondriacs, and the worried well might report enough of these symptoms to qualify. This is a very fuzzy area, and there is considerable overlap with other diagnoses like fibromyalgia, Gulf War syndrome, somatization disorder, etc. If we are going to study the condition, we want to make sure we aren’t studying a mixed bag of other conditions. In one study, 33.7% of healthy controls fulfilled the Fukuda definition.
New diagnostic criteria
The proposed diagnostic criteria for ME/CFS diagnosis requires that the patient have the following three symptoms:
- A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest, and
- Post-exertional malaise,* and
- Unrefreshing sleep*
At least one of the two following manifestations is also required:
- Cognitive impairment* or
- Orthostatic intolerance
* Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.
A new name
They say the name “chronic fatigue syndrome” has done a disservice to many patients, and the name “myalgic encephalomyelitis” fails to describe the major features of the disease. They propose renaming it “systemic exertion intolerance disease,” a name that they think more fully captures the full scope of the disorder.
Problems with diagnostic categories
Unexplained symptoms are common and frustrating. Doctors have always been puzzled by patients who complained of fatigue and a variety of associated symptoms without any identifiable pathological cause. Today’s CFS patients would once have been diagnosed with neurasthenia, a diagnosis that has been abandoned. “Fad” diagnoses wax and wane in popularity as both patients and doctors strive to give unexplained symptoms a satisfying name.
The same constellation of symptoms might be variously diagnosed by different mainstream and alternative medical providers as CFS, fibromyalgia, chronic Lyme disease, Gulf War syndrome, post-traumatic stress disorder (PTSD), multiple chemical sensitivity, environmental sensitivity, candidiasis, and any number of fake diseases. However the symptoms start, they quickly become complicated by deconditioning. As patients exercise less, they become less able to exercise. Muscles atrophy with disuse, endurance declines. Confirmation bias sets in. The sick role becomes a self-fulfilling prophecy. Whatever the underlying pathology, the degree of suffering is affected by psychological factors. It is devilishly difficult to sort out the physical from the psychological and to know how best to help these sufferers. Current treatments are not very effective.
When does a group of symptoms become a syndrome or a disease? We do our best to divide human suffering into categories and apply labels, but in the absence of valid diagnostic tests and pathophysiologic explanations, we are working in the dark. At this point, we don’t have conclusive evidence, we only have the best educated guesses of experts based on the limited evidence we do have.
Whatever we call it, I think it is inevitable that until we have a better understanding of this condition (or conditions?) it will be over-diagnosed by some doctors, some patients will self-diagnose inappropriately, and research will continue to be problematic. Anything we can do to make the diagnosis more precise will be welcome. The IOM proposals are a step in the right direction.