Doctors struggling to sort through the profound fatigue, unrefreshing sleep, and other nagging symptoms that might raise the possibility of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can access some updated diagnostic guidance from a recently released Institute of Medicine (IOM) report.
The disease, which is frequently misdiagnosed and still the object of some skepticism, can be diagnosed through a history and physical exam focused on several specific symptoms, the report's committee members wrote. Studies show that the disease has a physiologic basis, they stressed, with the hallmark symptom of post-exertional malaise. To that end, they proposed a new, and in some quarters controversial, name to replace its predecessor: systemic exertion intolerance disease.
“The key message is that many doctors mistakenly believe that chronic fatigue syndrome is a psychological problem—it is malingering; it is not real; there's no objective evidence—and that patients should be dismissed as being not truly ill,” said Theodore Ganiats, MD, a family physician and committee member, who also wrote a related piece published online Feb. 10 in Annals of Internal Medicine summarizing the committee's findings.
“Not all doctors think that, but many doctors do,” said Dr. Ganiats, a professor in the department of family medicine and community health at the Miller School of Medicine at the University of Miami. “We found an incredible amount of evidence that this is a real disease. It is a real disease without a biomarker as of yet.”
The committee, charged to focus on diagnosis only and not treatment, was tackling a disease that impacts the daily lives of an estimated 836,000 to 2.5 million Americans. But the vast majority of adults so afflicted—some to the extent that they can't change their clothes without becoming fatigued—don't know the source of their misery. At least 84% haven't yet been diagnosed, making it impossible to quantify the prevalence of ME/CFS, according to the report. Among those who are diagnosed, for one-third it takes at least 5 years and sometimes much longer, according to a survey involving 256 people conducted by the CFIDS Association of America in early 2014.
Doctors are similarly operating without guideposts. Fewer than one-third of medical schools include information about ME/CFS in their curricula, according to a study cited in the IOM report. There are no targeted drugs and no clinical guidelines, and yet patients badly need both symptomatic and emotional relief from what can be an isolating disease, said Alan G. Pocinki, MD, FACP, an internist in Washington, D.C., who has studied ME/CFS since 1987.
“It's sad when people say things like, ‘I wish I had cancer. I wish I had heart disease,’” he recounted. “‘I wish I had something that would make other people appreciate that I was sick, and I wouldn't have to convince people that I was sick.’”
The IOM committee's proposed criteria, which it hopes will streamline diagnosis, highlight a shorter list of symptoms than the criteria most commonly used to date. First developed and published by Fukuda and colleagues in 1994—and thus sometimes called the Fukuda definition—the existing guidance states that the fatigue must be significant, extending more than 6 months. The patient also must report at least 4 of the following 8 symptoms:
- post-exertional malaise lasting more than 24 hours,
- unrefreshing sleep,
- significant impairment of short-term memory or concentration,
- muscle pain,
- pain in the joints without swelling or redness,
- headaches of a new type, pattern, or severity,
- tender lymph nodes in the neck or armpit, and
- a sore throat that is frequent or recurring.
The IOM committee's proposed approach stipulates a substantial reduction in function accompanied by fatigue, lasting longer than 6 months, along with 3 of the 8 symptoms listed as optional in Fukuda criteria (post-exertional malaise, unrefreshing sleep and cognitive impairment), and/or orthostatic intolerance.
One of the particularly convincing elements from the review of existing research was the significance of post-exertional malaise in distinguishing ME/CFS from other diagnoses, Dr. Ganiats said. “That exertion could be physical, it could be exercise,” he said. “It could be mental, like taking a test. It could be emotional, like arguing with a child. Anything that is exertion could trigger this exacerbation of the disease.”
One 2013 study prominently cited in the IOM report assessed the percentage of patients with ME/CFS who reported exertion-related symptoms compared with those without the disease. For example, 86% of those with ME/CFS said that minimal exercise made them tired compared with 7% in the control group. Nearly three-fourths of those with ME/CFS said they were mentally tired after the slightest effort compared with 4% of the controls. (These percentages include only participants who reported symptoms of at least moderate severity that occurred at least half of the time during the prior 6 months.)
But Leonard Jason, PhD, one of the authors of the 2013 study as well as numerous others cited in the report, worries that the new criteria might mistakenly indicate that patients with other diagnoses have ME/CFS. As one example, Dr. Jason pointed out that someone could in reality suffer from major depression and meet the 3 primary symptoms, as well as report cognitive impairment.
But with a few more questions, a clinician should be able to distinguish a patient with depression from someone with ME/CFS, said Dr. Jason, a professor of psychology at DePaul University in Chicago. Patients with major depression, when asked what they would do if they suddenly felt better, would likely have an apathetic response, he said. If you posed that same question to someone with ME/CFS, he said, “They'll start giving you lists of things that they want to do.”
A doctor also can quickly cut to the chase to determine if patients are struggling with more than run-of-the-mill sleep frustrations, Dr. Pocinki said. Ask when they last awoke feeling refreshed, he suggested. “If somebody says, ‘Oh, I can't remember the last time I felt rested,’ or ‘I don't know what that would feel like, I'm always tired,’” he said, “then that's more than just somebody who has been working too hard and not getting enough sleep.”
Want to get a more nuanced sense of fatigue's impact? Ask specifically if patients have been forced to cut back on hobbies or other outside activities or have had to reduce their work hours, said Dr. Pocinki, a clinical associate professor of medicine at George Washington University.
In the IOM report, the diagnostic criteria are followed by several pages of related questions that doctors can ask to distinguish ME/CFS from other potential causes. While Dr. Pocinki said the list is terrific, he questions whether its length might prove daunting to a time-pressed primary care doctor.
Moreover, the proposed list of symptoms, albeit shorter, is “more complex if you will,” Dr. Pocinki said. Doctors are accustomed to asking about symptoms like joint pain, muscle pain, and headache, which figure in the Fukuda definition, he said. They are likely to be less acquainted with concepts like post-exertional malaise and orthostatic intolerance.
But Lucinda Bateman, MD, a member of the IOM committee and a general internist in Salt Lake City who runs a fatigue clinic there, said that the report provides a wealth of detail to elaborate on the short boxed list of proposed diagnostic criteria. “I worry a little bit that people will just look at the surface,” she said, stressing that doctors will need to be educated and trained in the new approach.
“It is not hard to diagnose this illness,” she said. “But most of these criteria are not routinely elicited in an interview and physical exam.”
If your patient has the symptoms, he or she probably has the disease, Dr. Bateman said. But as with any diagnostic scenario, doctors should perform due diligence in excluding other potential causes of fatigue and other symptoms, she noted. Also, doctors shouldn't exclude patients from having the disease if they have other conditions, such as diabetes, she said.
In fact, given that the Fukuda definition does exclude other conditions, Dr. Bateman predicts that prevalence rates could increase if the new criteria are put into practice.
Treating ME/CFS is similar to caring for patients with fibromyalgia, Dr. Pocinki said. “It's often all about breaking the cycle of chronic pain, poor sleep, fatigue, and depression, with the added complexity of autonomic dysfunction affecting all four,” he said. “Each one of those things makes the other ones worse.”
A good start is addressing sleep difficulties, said Dr. Pocinki, who noted that the committee designated unrefreshing sleep as a major symptom. “If you can't get a restful night's sleep, your fatigue is never going to get better.”
The sleep disturbances in these patients can appear as shallow sleep or hyperarousal. Dr. Pocinki described a patient who had 177 such arousals, brief disruptions in the continuity of sleep, in a 6-hour sleep study. Some types of medications, such as beta-blockers or clonidine, are often successful in limiting those episodes, he said.
Addressing sleep issues also involves uncovering other related issues, such as pain or depression, Dr. Pocinki said. In most patients, it's reasonable to try an antidepressant to see if it's helpful in easing sleep, lack of energy, and other symptoms, said James Griffith, MD, FACP, a professor of internal medicine and psychiatry at West Virginia University School of Medicine in Charleston, who also has researched the disease.
“I also try to explain to my patients, ‘This is really not depression that you have. This is a distinct disorder from depression,’” he said. Cognitive behavioral therapy might be helpful as well in assisting patients to better understand the limitations of their disease and ways to cope with the ups and downs of symptoms, Dr. Griffith said.
At this point, it's unclear what percentage of ME/CFS patients will significantly improve, as there are no comprehensive population-based data, Dr. Bateman said. “We honestly don't know how many people get better, because they go off the radar,” she said. “We have no idea what the true prognosis is.”
In Dr. Pocinki's personal clinical experience, he's seen many patients return to work, although at a lesser intensity. Overall, he estimates that 10% to 15% of his patients fully recover, one-third significantly improve, another one-third improve more slowly, and the final 10% to 15% will likely remain disabled long term despite his efforts.
Primary care doctors can make a difference in these patients' lives, given that they are used to treating the various symptoms involved, Dr. Pocinki said. Dr. Jason agreed and said that family doctors will also need to assume a role, given the limited number of ME/CFS specialists.
“Don't dismiss these patients,” Dr. Jason said. “Do a complete workup because you might find out the cause of their fatigue, whether it's anemia or something else.”
Above all, treat these frustrated patients with sensitivity despite the lack of a conclusive diagnostic test or marker, he said. “Remember that the vast majority of lower back pain is unexplained, but we still treat those patients with compassion.”