Our disease is plagued by too many case definitions, with the Institute of Medicine’s Systemic Exertion Intolerance Disease (SEID) being the most recent. Our federal agencies are thus far continuing the agnostic position of accepting whatever case definitions are proposed by researchers or drug sponsors. Communication from the IOM panel members has seemed contradictory at times regarding whether SEID replaces ME, or what to do with patients who do not meet SEID criteria. And advocates are arguing with each other over which definition is “right” and whether to support SEID. This includes some advocates claiming ME is not SEID, and that these two diseases should be kept separate.
This controversy gets to the heart of the IOM report, and the heart of its use and dissemination. It’s not possible to cover all aspects of this controversy in one blog post. Instead, I would like to come at it a different way. Rather than talk about the differences among these criteria, let’s consider the flip side problem of patients who meet more than one case definition. I’ll use myself as an example, and apply the major definitions. Then I’ll talk about a way to think about the muddle we’re in. For a nice overview of the definitions, see chapter 3 of the IOM report. Dr. Cindy Bateman also gave a great talk about SEID that explains some of the IOM Panel’s thinking behind the definition.
Ha! Just kidding! You know what I think of the Oxford definition. Let’s move on.
- Prolonged or chronic fatigue that persists or relapses for ≥ 6 months
- Four or more of the following concurrently present for ≥ 6 months: impaired memory or concentration; sore throat; tender cervical or axillary lymph nodes; muscle pain; multi-joint pain; new headaches; unrefreshing sleep; post-exertion malaise
When I was diagnosed in 1995, I met these criteria including having all eight of the ancillary symptoms (plus a number of others like dizziness, fevers, etc). Today, I have the fatigue plus impaired concentration, muscle pain, joint pain, unrefreshing sleep and PEM every day. I still occasionally get sore throats, headaches and tender lymph nodes (and dizziness, orthostatic intolerance, etc). So I meet the Fukuda definition.
One thing to keep in mind is that Fukuda draws a really big circle. At the P2P Workshop in December 2014, Dr. Luis Nacul presented data that show 163 different symptom combinations are possible under Fukuda. When PEM is required, that number drops to 35 combinations (still very high). There is no question that there are people who will meet Fukuda but will not meet IOM SEID or the ME definitions. Therefore, I am not arguing that Fukuda CFS is equivalent to CCC or ICC or SEID.
Canadian Consensus Criteria ME/CFS
- Post-exertional malaise and/or fatigue
- Sleep dysfunction
- Two or more neurological/cognitive manifestations
- At least one symptom from two of the following categories: Autonomic; Neuroendocrine; Immune
- Illness lasting ≥ 6 months
Yes to fatigue, PEM, sleep dysfunction, pain, neurocognitive (such as confusion, concentration/memory, disorientation, info processing, word retrieval, overload phenomena), autonomic (such as POTS, lightheadedness nausea, IBS), neuroendocrine (such as feverishness, temperature intolerance, loss of adaptability), immune (such as sore throat, flu like symptoms, tender lymph nodes), and obviously I meet the 6 month requirement (with an extra 20 years to boot). So I easily meet the Canadian Criteria.
International Consensus Criteria ME
- Post-exertional neuroimmune exhaustion (PENE)
- At least one symptom from three of the following four neurological impairment categories: Neurocognitive impairments; Pain; Sleep disturbance; Neurosensory, perceptual and motor disturbances
- Immune, gastro-intestinal and genitourinary impairments. At least one symptom from three of the following five categories: Flu-like symptoms; Susceptibility to viral infections with prolonged recovery periods; Gastro-intestinal tract; Genitourinary; Sensitivities to food, medications, odors or chemicals
- At least one symptom from energy production/transportation impairments: Cardiovascular; Respiratory; Loss of thermostatic stability; Intolerance of extremes of
I clearly have PENE according to the definition in the ICC paper, at the moderate (mostly housebound) level with occasional severe (bedbound) episodes. For the neurological impairments, I have difficulty processing information and short-term memory loss, headaches and significant widespread pain, unrefreshing sleep and disturbed sleep patterns, and I have the sensory and motor disturbances.
For the immune impairments category, I have flu-like symptoms, nausea/IBS, and sensitivity to medications and odors. In energy production, I have orthostatic intolerance, dizziness, air hunger, recurring feverishness, and temperature intolerance. So I easily meet the ICC definition.
- 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,
- Post-exertional malaise, and
- Unrefreshing sleep
- At least one of the two following manifestations is also required: Cognitive impairment or Orthostatic intolerance
Importantly, these symptoms must be present at least half the time, and with at least moderate intensity. This is not a bad night’s sleep or minor forgetfulness. Not surprisingly, my doctor confirmed at my last office visit that I clearly meet the IOM SEID criteria, too.
So, Do I Get Bingo?
Where does that leave me? I meet criteria for Fukuda CFS, CCC ME/CFS, ICC ME and IOM SEID. You tell me: do I have one disease or four diseases?
This is the problem confronting all the advocates who are claiming that SEID is not ME. Many patients, like me, will meet the criteria for both. And when this point is raised in discussion, some people have suggested that there are two separate diseases. But if you follow that idea to its logical conclusion, two diseases means two different revenue streams for NIH funding. It also means a drug approved for one disease will need to be approved for the second disease.
If we are talking purely about case definitions, as opposed to real people, then yes ME is absolutely not SEID because the ICC and IOM SEID are different criteria. ICC requires more symptom categories, and specifies the symptom manifestations in each category. And neither ICC ME nor IOM SEID are Fukuda CFS. Dr. Lenny Jason’s most recent paper is just one illustration of that. So if we are purely talking about the definitions – the separate descriptions of requirements for diagnosis – then I think it is logical and clear that ME is not SEID is not CFS.
But that’s not the only context for discussion. Case definitions are hypothetical until they are applied to real people. And when you apply those four definitions to me, I meet them all. This does not mean I have four diseases. It means that these four definitions each describe the disease that I have. Do you see the distinction?
That is the crux of the matter. This thing, this disease that we have, the disease we described to FDA, the disease we can recognize in each other in about five minutes – this thing has been described (with varying degrees of success) by all four criteria. Fukuda CFS is clearly the broadest and least useful definition. Fukuda allows too many combinations of symptoms, and only a fraction of those include PEM. Therefore, it is possible to meet Fukuda and not meet IOM SEID, and what to do with those patients is a quandary for another discussion.
But to claim that IOM SEID is not ICC ME is not CCC ME/CFS is true only in the literal sense that these criteria do not use the same words to describe the disease state that I have, and that many of my readers have. It may be possible to meet one of these descriptions and not another, but that does not automatically mean we all have different diseases, especially when the overlaps among those descriptions seem so large.
I have one disease. That disease has been described in different ways by different groups. The intersection of those descriptions and our experiences as patients must be studied. We need data to understand the characteristics of the patient populations identified by each definition. There will likely be substantial overlap – but is there a biomarker that unites us? Are there subtypes that distinguish us? Is one description demonstrably more sensitive and specific than the others? Did IOM SEID successfully pare down to the most essential elements of the disease, or did they strip out too much?
I have one disease. That disease has been described in different ways. I want my disease to be researched so that the less accurate and less useful descriptions can be retired.