PHOENIX RISING

CFS Prevalence The CDC then applied these criteria to a new kind of intensive random telephone sampling scheme of people in urban, metropolitan and rural Georgia. Instead of asking whether someone in the household was fatigued they asked if there was someone who was ‘unwell’. Dr. Reeves explained, ‘as we have learned more, we understood that fatigue is not the only thing that bothers people with CFS. People also report, “I hurt, can’t think clearly, feel crappy when I wake up”. So we changed the screening algorithm to get people who are ‘unwell’. It turns out that a substantial number of those with cognition problems have CFS. We cast a bigger and more sensitive net and got a larger number’ (CFSAC Meeting July ’06) They called almost 11,000 numbers and did detailed interviews with people who had a variety of types of unwellness.

At the end they got 292 CFS patients (according to the old definition), 268 chronically unwell patients, 60 people with short-term unwellness and 163 well people to come to the clinic for an examination. At the clinic they examined them more closely, did laboratory tests to determine if they had any diseases that precluded them from being in a CFS research study and then recategorized them using the empirical definition. They analyzed them and came up with new estimates of CFS prevalence.

A New Kind of CFS Patient: It’s been clear for quite some time that this new definition would uncover a new kind of CFS patient. Two years ago CDC researchers found the Empirical Definition increased the number of CFS patients almost three-fold. But it doesn’t simply add patients to the mix it also appears to kick a substantial number of ‘CFS patients’ out of it. According to table two of the present paper about 45% of people formerly classified during a telephone interview as having CFS under the old definition would not have ‘CFS’ under this new definition. Indeed the 2005 Empirical Definition study found ‘little agreement’ between the groups of patients identified by the Fukuda and ED criteria.

A Sicker Group! The patients singled out by the empirical definition were clearly quite ill. The Reeves group noted that this group had “lower scores on all scales except physical function and general health than patients with congestive heart failure.”

Surprisingly (given the increased prevalence figures) the new definition defines a sicker group of people than does the old Fukuda (International) definition. Statistical tests using all eight SF-36, 5 MFI tests and 19 symptom test scores indicated that in general that the most ill patients usually ended up being placed in the CFS category, the next most ill were in the CFS-like category and so on. This was a distinct improvement over the International definition.

Defining CFS or Something Else? But were they CFS patients? Despite the Reeves group success at identifying a sicker group that displays more consistency over time with regards to their illness than the old definition, several researchers have raised substantial questions regarding the new definition.

Dr.Jason, a well-known CFS researcher noted that “It is very possible that this new empirical classification does identify a group of individuals with high levels of fatigue, impairment and symptoms but” and here’s the rub ‘ it might also be identifying a group with high chronic distress and illness rather than CFS as a unique disorder”.   

FOUR QUESTIONS. Four main questions have been raised:

1. Should emotional disability be given the same weight as physical or social disability in a CFS definition?

2. Should low activity levels (apart from fatigue) be used to define CFS?

3.  Is a low (median) cutoff point for fatigue/activity suitable?

4. Are the symptom criteria set high enough? 

Along with Dr. Jason, two reviewers, Dr. White and Dr. Lloyd, raised these questions in their prepublication comments. 

1. The Emotional Subscale Used is Inappropriate. This definition allows people who believe their distress to be primarily due to  emotional causes to qualify for one of the three major  criteria for CFS. Both White and Jason argue that the emotional subscale should not have been included. Historically, emotional components have not played a major role in defining CFS.

Dr. Jason pointed out that CFS patients typically rate themselves very poorly in ‘physical functioning’ but under this  scheme someone could score fine in ‘physical functioning’ but qualify for CFS by scoring poorly in the emotional category. Dr White, a psychiatrist, pointed out that the CDC’s own studies indicate that ‘role emotional’ does not appear to play a prominent role in CFS. Several other studies have failed to find a strong emotional component to CFS.

Dr. Jason and Dr. White also noted how similar the prevalence figures under the new definition are to the prevalence figures found in the UK using a definition (Oxford) that appears to select for patients with increased rates of psychological disorders. Oxford study patients also have  decreased rates of post-exertional fatigue (63%) and sleep problems (64%). Since these are core components of the Canadian Consensus definition at least a third of these patients would not qualify for CFS under its criteria. It would be difficult to uncover the cause of post-exertional malaise in a study group with the Oxford makeup.

Rationale: Why include the emotional subscale when your own tests do not suggest it is central in CFS? When prodded by Dr. White, Dr. Reeves said ‘we included the emotional subscale to capture the relation between the functional emotional impairment and reduced social and personal activities”. This suggests Dr. Reeves wants to capture that set of unwell people whose emotional problems impair them from partaking in social and personal activities.

Could Dr. Reeves be right in his sense that the emotional component has been underemphasized in CFS? One can hardly argue that CFS does not have an emotional effect; rates of mood disorder do, after all, soar as people come down with CFS and few with CFS would probably argue that they are, physical problems aside, the same person emotionally they were prior to coming down with CFS. The early ME studies again and again emphasize the emotional turmoil inherent in that disease; a turmoil that appears to go far beyond that associated simply with being ill. While the Canadian Consensus Definition does not make emotional problems a major criterion it does include ‘emotional overload’ in one category and notes the panic, anxiety and emotional problems that can occur in CFS.

An emotional component to CFS would not be surprising given what we are learning about the central nervous system abnormalities in CFS. They appear to be centered in areas of the brain involved in both mood regulation and cognition (as well as autonomic nervous system functioning, metabolism, fatigue and pain). Given that, it might be surprising if, along with cognitive and physical problems, CFS wasn’t also associated with emotional difficulties. Throw in the increasing evidence that infection may be at the heart of some cases of mood disorder and one can easily visualize a scenario that satisfies everyone sitting at the CFS table. In the end it may be that every one, the psychiatrists, the immunologists, the neurologists, etc., will be at least partially right about CFS.

The question, of course, is where do you draw the line? Simply including an emotional component should, of itself, not dramatically alter the makeup of CFS patients.

Giving emotional distress the ability to fulfill one of the three legs of the new CFS definition does, however, elevate the role ‘emotion’ potentially plays to a new level. There has been a physicality inherent in CFS that has lead CFS patients (in contrast to depressed patients) to tenaciously assert an organic cause to their disease.

2. Fatigue is not a necessary component of the definition. In the end Dr. White did not believe the emotional subscale question was the major issue. Both he and Dr. Lloyd, the other prepublication reviewer, felt a more important issue involved the fatigue ratings.

Because CFS patients must either report general fatigue or reduced activity this is the first definition of CFS that does not explicitly require that severe fatigue be present. In his review White states “this means it would be possible to meet the fatigue criterion without significant fatigue”. Jason reports this opens the door for people with reduced activity levels not due to fatigue but to emotional problems (depression) to meet the criteria for CFS.

3. The cutoff points for fatigue and activity were not low enough – In order to qualify for being highly fatigued or very inactive a patient simply had to score at or below the median. (The median point is the middle point in a gradient of numbers)

Why define a disease that has historically been characterized, rightly or wrongly, by fatigue, using a median cutoff point?. The Reeves group stated they based their conception of fatigue on the 1994 International definition but it’s hard to believe the authors of that document had in mind a median level of fatigue when they stated “in our conception of the chronic fatigue syndrome, the symptom of fatigue refers to severe mental and physical exhaustion”.

When the editors of the Journal of Population Health Metrics questioned this cutoff point, Dr. Reeves noted that CFS-like patients had to report that they were “were fatigued, had been fatigued for at least six months and that rest did not relieve their fatigue” and that “Fatigue was mandatory for the diagnosis of CFS in this study.”

Yet it’s hard to understand how this could be so. The interview process asked about unwellness not fatigue. Once the different groups (including the non-fatigued group) were brought together and re-classified according to the Empirical Definition criteria, fatigue was no longer a necessary component. According to one table approximately 15% of the ‘new’ CFS patients reported they did not have problems with fatigue during the telephone interview.

4. The cutoff points for the symptom severity are not high enough – Dr. Jason pointed out that someone could meet the criteria for CFS who reported that only two of eight symptoms (fatigue, muscle/joint pain, headache, sore throat,  unrefreshing sleep, swollen lymph nodes, problems concentrating), one of moderate and the other of severe severity, were present all the time.

Counterpoint: Several aspects of the definition suggest that the projected flood of very emotionally distressed people into CFS studies may not materialize. The exclusion criteria that exclude patients who have had major depression in the past five years from participating in CFS research studies should filter out some of these patients.  (The CDC has not been consistent in this matter; the Wichita CDC studies included them, the Empirical definition and this latest paper excluded them altogether.)

(Although major melancholic depression is excluded, 'ordinary' depression, anxiety disorders and somatoform disorders are not.)

THE FUTURE

A Depressing Future? At the 2007 IACFS conference Dr. Jason reported that a preliminary study found that 40% of patients with major depression qualified for CFS under the new definition. This, of course, suggests that future CFS studies by the CDC could have a greatly increased component of emotionally distressed patients. Dr. Jason suggested that this has already occurred; the recent Heim study that employed the empirical definition found that 62% of the CFS patients had evidence of early childhood abuse of one type or another. This contrasted with a study employing the Fukuda criteria that did not find such high levels of childhood abuse.

This is, of course, the crux of the matter; if the new definition allows a significant number of people who don’t have CFS but do have emotional or other problems into research studies, then CFS research could be set back for decades. One can argue that the vagueness of the 1994 definition probably allowed a subset of people with mood disorders or other diseases but not CFS into research studies and that this is one reason for the inconsistent findings that have plagued some aspects of the CFS research for the past 13 years.

*Check Out an Interview with Dr. Leonard Jason on the Empirical Definition