(You can read and/or download the report as well as watch the video of the announcement HERE. You can get the gist of the report by reading the Summary at the beginning, or Recommendations on page 209.)
Much like its previous report on Gulf War Illness, the IOM's report on ME/CFS has generated a tremendous amount of media coverage (Time, CBS, NY Times Blog, ABC), as well as spirited discussion in the ME/CFS community. While mainstream organizations have welcomed the report's emphasis on the serious nature of the disease, there are some lingering doubts about the appropriateness of the new name, "systemic exertion intolerance disease" (SEID), as well as the viability of the new definition.
The report made four recommendations:
Recommendation 1: Physicians should diagnose myalgic encephalomyelitis/chronic fatigue syndrome if diagnostic criteria are met following an appropriate history, physical examination, and medical work-up. A new code should be assigned to this disorder in the International Classification of Diseases, Tenth Edition (ICD-10), that is not linked to “chronic fatigue” or “neurasthenia.”
Recommendation 2: The Department of Health and Human Services should develop a toolkit appropriate for screening and diagnosing patients with myalgic encephalomyelitis/chronic fatigue syndrome in a wide array of clinical settings that commonly encounter these patients, including primary care practices, emergency departments, mental/behavioral health clinics, physical/occupational therapy units, and medical subspecialty services (e.g., rheumatology, infectious diseases, neurology).
Recommendation 3: A multidisciplinary group should reexamine the diagnostic criteria set forth in this report when firm evidence supports modification to improve the identification or care of affected individuals. Such a group should consider, in no more than 5 years, whether modification of the criteria is necessary. Funding for this update effort should be provided by nonconflicted sources, such as the Agency for Healthcare Research and Quality, through its Evidence-based Practice Centers process, and foundations.
Recommendation 4: The committee recommends that this disorder be renamed “systemic exertion intolerance disease” (SEID). SEID should replace myalgic encephalomyelitis/chronic fatigue syndrome for patients who meet the criteria set forth in this report. [Italics mine throughout]
Some Background: The IOM's Charge
The IOM is an independent nonprofit organization founded in 1970. As health arm of the National Academy of Sciences, it works outside of the federal government to provide "unbiased and authoritative advice" to decision makers and the public. Because it is not part of the federal government, its decisions to not constitute policy. No branch of HHS is obliged to follow its recommendations.
In 2013, HHS contracted the IOM to evaluate the current criteria for diagnosis of ME/CFS and recommend clinical diagnostic criteria that would "address the needs of health care providers, patients, and their caregivers."
Specifically, the committee was asked to:
• conduct a study to identify the evidence for various clinical diagnostic criteria for ME/CFS using a process with input from stakeholders, including practicing clinicians and patients;
• develop evidence-based clinical diagnostic criteria for ME/CFS for use by clinicians, using a consensus-building methodology;
• recommend whether new terminology for ME/CFS should be adopted; and
• develop an outreach strategy for disseminating the new criteria nationwide to health professionals.
The committee was also asked to distinguish among disease subgroups, develop a plan for updating the new criteria, and make recommendations for the plan’s implementation.
With the exception of the CAA (now Solve ME/CFS Initiative) the immediate reaction to the million-dollar IOM contract was negative. Fifty of the world's leading experts in ME/CFS wrote a letter to then Secretary of HHS Kathleen Sebelius endorsing the Canadian Consensus Criteria (CCC) a definition based on "scientific knowledge gained from decades of research. " The letter also warned that the contract "would move ME/CFS science backward by engaging non-experts in the development of a case definition for a complex disease about which they are not knowledgeable." (You can read the letter HERE.) The letter was supported by hundreds of advocates, as well as petitions which garnered 10,000 signatures.
Analysis in a nutshell
- The report clearly states that ME/CFS is a complex a "serious, chronic, complex, multisystem disease that frequently and dramatically limits the activities of affected patients.
- The report recommends abandoning the name "chronic fatigue syndrome."
- The report recognizes that research funding has been inadequate.
- The report recommends a definition that is simplistic, undermining the statement that ME/CFS is a "complex, multi-system disease."
- By limiting diagnosis to four or five non-specific symptoms, the IOM definition, like the Fukuda definition, will capture people without ME/CFS.
- The core symptoms of the new diagnosis fit into the clinical definition for anxiety with depression.
- Exertion intolerance has been, and will be, interpreted by physicians as a psychiatric manifestation of "fear avoidance" of exercise.
- The name "systemic exertion intolerance disease" reduces ME/CFS to a single symptom.
- The inclusion of "systemic" in the name is meaningless. All diseases are systemic.
- Exclusionary diagnoses are no longer ruled out, which means patients with early MS, Hashimoto's, lupus, mitochondrial disease, Ehlers-Danlos and other treatable but hard-to-detect illnesses may receive a false diagnosis of SEID.
In-depth analysis of the report
Excellent overview of the research
On the whole, the report did a very good job of discussing the research pertaining to diagnosis, subgroups, symptoms clusters, as well as documenting key problems such as lack of funding for research, and inadequate coverage in medical schools. Anyone taking the time to read the entire report would have a clear view of the types of problems faced by the ME/CFS community. (One of those problems is the constant confusion between "chronic fatigue" and CFS, a problem which the IOM perpetuated by citing studies on "chronic fatigue.")
Abandonment of "chronic fatigue syndrome"
After a healthy discussion of all the reasons why CFS is a poor name for the disease, the IOM concluded that "the term 'chronic fatigue syndrome' often results in stigmatization and trivialization and should no longer be used as the name of this illness" (p 60). The report goes on to say that "ME/CFS should not be considered merely a point on the fatigue spectrum or as being simply about fatigue. [...] Other factors, such as orthostatic intolerance, widespread pain, unrefreshing sleep, cognitive dysfunction, and immune dysregulation, along with secondary anxiety and depression, contribute to the burden imposed by fatigue in this illness."
Recognition of 2-day CPET as an objective measure of ME/CFS
The IOM report recognizes PEM as one of the defining characteristics of ME/CFS (though the report also mentions that PEM is experienced by patients with MS and major depression). Citing the Keller and Snell studies, the report supported the 2-day CPET protocol "as an objective indicator that physical exertion may decrease subsequent function in some ME/CFS patients. By contrast, a single CPET may be insufficient to document the abnormal response of ME/CFS patients to exercise" (p 84).
Recognition of cognitive impairment and brain abnormalities
The IOM reviewed the past ten years of research on neurocognitive impairment and brain abnormalitites, and did a credible job of summarizing them. While the IOM did not draw any conclusions from the brain studies it examined (including the recent Nakatomi study on brain inflammation, but omitting the Stanford study) the committee did state that "There is sufficient evidence that slowed information processing is common in patients with ME/CFS, and a growing body of evidence shows that it may play a central role in overall neurocognitive impairment associated with the disease. Such a deficit may be responsible for the disability that results in loss of employment and loss of functional capacity in social environments" (p 106).
Recognition of immune dysfunction
After a review of NK cell toxicity and immune activation studies the IOM concluded that "Sufficient evidence supports the finding of immune dysfunction in ME/CFS" (p 153).
Acknowledgment of pediatric ME/CFS
"There is sufficient evidence that orthostatic intolerance and autonomic dysfunction are common in pediatric ME/CFS; that neurocognitive abnormalities emerge when pediatric ME/CFS patients are tested under conditions of orthostatic stress or distraction; and that there is a high prevalence of profound fatigue, unrefreshing sleep, and post-exertional exacerbation of symptoms in these patients. There also is sufficient evidence that pediatric ME/CFS can follow acute infectious mononucleosis and EBV" (p 201).
Recognition that research funding has been inadequate
"Remarkably little research funding has been made available to study the etiology, pathophysiology, and effective treatment of this disease, especially given the number of people afflicted" (p 9).
The Bad: Non-Specific Definition
The IOM report sends mixed messages to medical professionals. On the one hand, it states that ME/CFS is a "serious, complex" disease. But on the other, it presents diagnostic criteria that are oversimplified, giving the impression that this is not a serious, much less potentially fatal, illness. Of the two messages, the second will have the greater weight. Regardless of the encouraging language used in the report, medical professionals are much more likely to read a short definition than a 282-page document.
The new IOM definition is a highly reduced version of the Canadian Consensus Criteria, consisting of three non-specific (i.e. common to many illnesses) required symptoms, and two non-specific optional symptoms. Because it consists of non-specific symptoms, the IOM definition will capture a number of illnesses in addition to ME/CFS, making it useless for research and too broad for diagnosis. (This is precisely the problem with the Fukuda definition.)
(Contrary to popular belief, PEM is not unique to ME. Patients with early MS, B12 deficiencies, Hashimoto's disease, and lupus all experience a worsening of symptoms after exertion. Regardless of the severity and permutations of PEM, physicians will not see the fine points. Nor will they ever consider a worsening of symptoms after emotional or cognitive stress to be anything other than psychosomatic.)
Diagnosis of ME/CFS requires that a patient have the following three core symptoms:
- A substantial reduction or impairment in the ability to engage in pre-illness levels of activities that persists for more than six months and is accompanied by fatigue - which is often profound - of new or definite onset, not the result of ongoing excessive exertion and not substantially alleviated by rest
- The worsening of patients’ symptoms after any type of exertion - such as physical, cognitive, or emotional stress - known as post-exertional malaise
- Unrefreshing sleep
- Cognitive impairment
- The inability to remain upright with symptoms that improve when lying down - known as orthostatic intolerance
The first symptom is still six months of fatigue. The IOM report states, "This 6-month requirement is supported by Nisenbaum and colleagues (1998), who showed that unexplained fatigue lasting for more than 6 months was related to symptoms included in the ME/CFS case definitions and that most other causes of similar fatigue do not last beyond 6 months." This implies that most cases of "similar fatigue" are self-resolving. In fact, the Nisenbaum study did not find that similar fatigue from other causes resolved within six months, because other causes of fatigue were not explored. The only conclusion Nisenbaum et al. reached was that six months the symptoms of CFS appeared to be a "threshold" for severity of symptoms. But their data indicated that this threshold was relatively modest, with percentages varying only slightly between the 1-5 month range and the 6-month or longer range.
Nevertheless, 6 months of "fatigue" is still required, which will miss all the sudden onset cases. This is problematic, because the initial "acute" phase of the disease is what is most puzzling to physicians. Patients who come to their doctors horribly ill several weeks after a "flu" are taken seriously, because the acute phase is quite dramatic. This is the phase in which test results (including ECGs and CBCs) are often abnormal, and in which physicians write prescriptions for numerous medications, none of which help and many of which harm patients. A case definition for a disease that can develop with such speed and severity should include a provision for sudden onset.
Six months of fatigue is still the predominant symptom in this definition, and because there are so few others, physicians will retain "chronic fatigue" as the go-to symptom for diagnosis. And because chronicity is established after six months, it is likely that physicians will dismiss patients with long-term fatigue in the absence of measurable signs, or combined with non-specific symptoms, as having psychological disorders.
The second symptom, PEM, will inevitably be interpreted as "exercise intolerance" by physicians. Exercise intolerance is a term that physicians understand, as it is commonly used in association with cardiopulmonary illnesses. Physicians may also interpret PEM as "avoidance of exercise," which, when combined with fatigue, sleep disorder, and cognitive problems (the result of lack of sleep) will lead them to think that a patient presenting these symptoms needs therapy or antidepressants.
PEM is non-specific. Contrary to popular belief, PEM is not unique to ME. Patients with early MS, B12 deficiencies, Hashimoto's disease, and lupus all experience a worsening of symptoms after exertion. Regardless of the severity and permutations of PEM, physicians will not investigate the fine points. Nor will they ever consider a worsening of symptoms after emotional or cognitive stress to be anything other than psychosomatic.
Doctors are taught in medical school to look for horses, not zebras, "horses" being common ailments, and "zebras" the more exotic or rare illnesses. In 2008, Drs. Philip R. Fischer, Jonathan N. Johnson, and Chad K. Brands wrote an an excellent article titled, "Fatigue, Exercise Intolerance, and Weakness: Lessons on Herding Zebras" in which they presented case studies demonstrating why physicians need to look beyond the obvious diagnosis. Of three pediatric cases in which the patients presented with typical symptoms of CFS, one had POTS, one had pheochromocytoma (benign adrenal tumor), and one had undiagnosed dermatomyositis (an inflammatory disease). All of these patients would meet the criteria for SEID.
Waking up tired, even after what may be considered adequate sleep, is universal in ME/CFS. It is also common in hypothyroidism, low adrenal function, fibromyalgia, narcolepsy, Lyme disease, allergies, sleep apnea and depression. Most doctors seeing a patient with the triumvirate of fatigue, unrefreshing sleep, and cognitive problems will conclude that the patient has depression, especially if standard blood tests are negative. The addition of "exertion intolerance" does not exclude depression, or distinguish ME/CFS from any number of illnesses in which an exacerbation of symptoms after exertion is a feature.
Cognitive Impairment and OI
The IOM included cognitive impairment as an optional symptom, even though "Impairments in cognitive functioning are one of the most frequently reported symptoms of ME/CFS" (p 96). Why cognitive impairment is optional is not clear, as it is one of the cardinal symptoms of ME/CFS.
Orthostatic intolerance was also included as an optional symptom, which is also puzzling. OI is usually included under autonomic dysregulation, which can also include other symptoms, such as migraine, temperature and blood pressure fluctuations, and other manifestations of autonomic dysfunction, all of which are found in patients with ME/CFS. There is also a tremendous overlap in symptoms between POTS (postural orthostatic tachycardia syndrome - the most common form of dysautonomia), and ME/CFS. (Anyone with POTS will fit the IOM definition of SEID, and vice versa,)
Although the committee did not examine etiology, they would have greatly benefited from reading Dr. Jay Goldstein's book, The Limbic Hypothesis, in which he theorizes (with substantial evidence) that damage to the limbic system causes the symptoms of ME/CFS. The hypothalamus, which controls the autonomic nervous system, is located in the limbic system. It is a tiny organ, easily damaged by high fevers, hypoxia, and neurotoxins, It would have benefited the IOM if they had understood some of the major theories behind the symptoms that they chose to include in their definition, even if it was not part of their charge. As the experts predicted, the IOM lacked "the needed expertise to develop “clinical diagnostic criteria” for ME/CFS."
The IOM stated that "Pain is a defining characteristic of ME/CFS ... The majority of ME/CFS patients experience some type of pain" (p 141). However, it rejected pain as a core symptom because because of the "less prominent role of myalgia in these patients relative to more core symptoms" (p 11). In making this statement, the IOM is overlooking their own research review. According to the studies the IOM reviewed, pain appeared with equal frequency to core symptoms.
The ultimate reason for rejecting pain was "while pain worsens ME/CFS when present, there is no conclusive evidence that the pain experienced by ME/CFS patients can be distinguished from that experienced by healthy people or those with other illnesses. Further, pain may be experienced in many areas, and while comprehensively assessing a patient’s pain symptoms is a challenging task, it is not specific to ME/CFS" (p 147).
Rejecting pain because it is non-specific ignores the fact that fatigue, exertion intolerance, sleep disorder, and the two optional symptoms are also not specific to ME/CFS. It also exhibits a failure to understand the basic physiology of pain. All pain is processed via the same neurological pathways, regardless of whether it is experienced by healthy people, or by people who are ill. Pain is a universal, and completely subjective, indicator that something is wrong in the body. The fact that so many people with ME/CFS experience pain cannot, and should not, be overlooked. To those who cannot escape it, pain is their most devastating symptom. Dismissing it as a significant feature of the illness basically relegates pain to "it's all in your head" (which, ironically, it is).
Exclusionary diagnoses not ruled out
Another major problem with the new criteria is that exclusionary diagnoses are no longer ruled out. Dr. Clayton was correct when she stated that there is nothing that says you can't get two conditions at the same time. You can have ME and hypothyroidism, or ME and cancer. Although Dr. Clayton was right in her assertion, a problem arises when you combine a lack of exclusionary diagnoses with a definition that requires only four non-specific symptoms. When patients present with these four symptoms, one of which is common to all diseases (fatigue), and there is no requirement that illnesses that match those symptoms (leukemia, Hashimoto's, Ehlers-Danlos, MS, lupus) be ruled out, there is the danger that patients who are "zebras" will be misdiagnosed.
There is also the strong probability that patients with major depression (MD) will be simultaneously diagnosed with SEID, which will be a roadblock for researchers as well as patients. Depression is a catchall for busy physicians who are presented with patients who primarily report fatigue and sleep disturbance. (And when their doctors ask, "Do you exercise regularly?" sleep-deprived patients usually say, "No, I am too tired.") As a number of studies have shown, patients with MD do not test the same as patients with ME/CFS. Because MD is not excluded from the diagnostic criteria, and because, like ME/CFS, there is no biomarker for depression, these patients will be included in studies. Some will then be shown to improve with exercise and therapy. (But not all. Because depression is a symptom of many underlying illnesses - hypothyroidism, autoimmune disease, cancer, diabetes - patients diagnosed with depression don't necessarily improve with exercise, therapy, or antidepressants.) Meanwhile, patients with ME will mistakenly be given antidepressants, which will only make them worse.
To prevent medical mismanagement of ME any diagnostic criteria must exclude major depression. And to secure appropriate treatment for diseases that are treatable, illnesses with similar symptoms must be ruled out.
Pediatric definition same as adult definition
It is a mistake to use the same definition for children and adults.
Pediatric ME is not the same as adult ME. Hypersomnia (sleeping round the clock) is more common in children than in adults. Symptoms present in equal severity (particularly stomach and headaches). Listlessness, ADD-like symptoms, double vision and other visual disturbances. and fever are also more common than in adults. Because their immune systems are ramped up, flu-like symptoms persist for much longer in children than in the adult population. All of these symptoms are easily observed by parents.
Six months of undiagnosed illness in a child can be devastating. It is also devastating to children when adults accuse them of "making up" their illness. The consequences of disbelief on the part of medical professionals and officials are that children are removed from their homes, placed in psychiatric institutions or foster care, where they are forced to suffer exercise and deprivation regimes that only make their illness worse. Any definition of ME for children needs to take these factors into account.
The IOM has described ME/CFS as a "serious, chronic, complex, multisystem disease," therefore it cannot, by its own description, reduce that "serious, complex" disease to four or five symptoms. To do so is a great disservice to the patients whose lives have been, and will continue to be, ruined by doctors who do not understand the illness, in part due to vague definitions.
What the IOM Should Have Done
Rather than invent a new definition, the IOM should have operationalized the algorithm devised by Jason's group, which has been tested and can identify patients with ME/CFS with 90% accuracy. The algorithm can be easily used by physicians as an initial screening tool once treatable conditions have been ruled out.
The second step in the diagnostic process should be the Canadian Case Definition, which not only provides enough detail to assess the illness, but utilizes the DePaul Symptom Questionnaire (DSQ) for additional information on severity and frequency of symptoms.
Until such time as we have a generally accepted biomarker, researchers should employ the CCC. It has been used in research for years, and has a verifiable track record.
The Absolutely Hideous
If the IOM failed in its charge to define the illness, it crashed and burned where naming it is concerned. Systemic Exertion Intolerance Disease is a name that means nothing. It is inappropriate, not just for this illness, but for any illness, for the following reasons:
1) All diseases are systemic, therefore the inclusion of "systemic" is meaningless. (The immune system, the endocrine system, and the nervous system all share cell receptors. Anything that affects one will affect the other two.)
2) "Exertion intolerance" will inevitably be translated into the more familiar term "exercise intolerance," which is seen in a number of illnesses. "Exertion intolerance" will be interpreted as either deconditioning or an "aversion" to exercise by general medical practitioners.
In addition to being useless, "SEID" represents a complete lack of familiarity with how diseases are normally named. Illnesses can be named according to a variety of traditions:
- Place where the illness was first identified: ex. Lyme Disease, Gulf War Illness
- Person, or people, who first described the illness: ex. Guillain-Barre, Alzheimer's
- Major organs or systems affected: ex. kidney disease, heart disease
- Primary mechanism or process: ex. muscular dystrophy
- Famous person with illness: ex. Lou Gehrig's
- Historical continuity: ex. Malaria (which means "bad air")
(For those who are keeping track, this is the IOM's second fiasco in recent memory. The first was in 2012 when it re-named Gulf War Illness - another complex illness without an accepted biomarker - as "chronic multisymptom illness." Objections raised to that name ultimately culminated in a retraction.)
What the IOM Should Have Done
There were two viable options open to the IOM for naming this disease.
1) Keep the historical name myalgic encephalomyelitis. This would have lent continuity to both research and diagnosis. And, in spite of all protestations to the contrary, the name is accurate. The IOM itself stated that pain is "a defining characteristic of ME/CFS" (p 141). There is also clear evidence of CNS damage.
2) Call it Ramsay's Disease. This would have honored the first person to extensively describe, and treat, the illness, Dr. Melvin Ramsay, as well as putting to rest to all the arguments about whether there is or is not inflammation in the brain.
Other options (such as picking a few prominent symptoms out of the pile. e.g. "systemic-fatigue-sleep-disorder-exercise-intolerance-cognitive-impairment-disease") are not practical or medically accurate and should not be considered.
In sum: Be careful what you wish for
For decades patients and ME/CFS specialists have complained about the derogatory name "chronic fatigue syndrome." The discussion of what to call this disease has raged since the term CFS was first coined in the 1980s, leading many people to assume that no matter what you called this illness it had to be preferable to CFS. "Get rid of CFS," they said. "Anything is better."
Now we have a new name, and it is no better - possibly even a little worse - than CFS.
For years, physicians and researchers have said that the Fukuda definition is too broad, and captures patients with other illnesses. They devised a new definition, which they used for 10 years. But, it was "too long." Now we have a new definition that is even more non-specific than the Fukuda definition, and, because the IOM does not rule out illnesses with overlapping symptoms, it will capture even more people without ME, making it useless for both diagnosis and research.
The IOM has lived up to the phrase "A camel is a horse designed by a committee." In the attempt to reach a consensus among bureaucrats, stakeholders and physicians, it has designed an ungainly beast.
To quote Jim Binns, chair of the Research Advisory Committee on Gulf War Veterans' Illnesses, "The conclusions of the report show that it was a waste of money, The committee never had the expertise or the process to do a case definition."