Review Prevalence of Chronic Fatigue Syndrome (CFS) in Korea and Japan: A Meta-Analysis, 2021, Lim and Son

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness accompanied by fatigue unsolved by rest. However, ME/CFS is a poorly understood illness that lacks a universally accepted pathophysiology and treatment. A lack of CFS-related studies have been conducted in Asian countries. This study aimed to estimate and compare the prevalence of ME/CFS in Korea and Japan and conducted a meta-analysis.

Methods: We searched PubMed, EMBASE, Cochrane, and KMBASE for population-based prevalence studies of the two countries and synthesized the data according to the Fukuda case definition.

Results: Of the eight studies (five in Korea, three in Japan) included, the total prevalence rate of Korean studies was 0.77% (95% CI 0.34–1.76), and 0.76% (95% CI 0.46–1.25) for the Japanese studies. The prevalence rate in females was approximately two-fold higher than males in Korean studies (1.31% female vs. 0.60% male), while the gender difference was less obvious in Japanese studies (0.76% female vs. 0.65% male).

Conclusions: Further epidemiology studies on the female ME/CFS prevalence rate between countries may be required.

Open access, https://www.mdpi.com/2077-0383/10/15/3204/htm

 

I wish researchers would stop using the Fukuda case definition.

 

Of course that would require wholly new large scale epidemiological studies - involving of course substantial costs. Studies such as this one are using existing data and cost little.

I think the larger problem is not the case definition but the reliance on self report via questionnaire, what is really needed is assurance of diagnosis that identifies the source of the diagnosis so that potential biases are explicit and can be interrogated.

 

Agreed. Self report by questionnaire may include people without ME, or in this case CFS.

However, large scale epidemiological studies need to be done.
They're done for other diseases: e.g. LH COVID etc.
ME has been ignored for various purposes.
Lack of data allows governments etc. to dismiss the scope, severity and impact this very debilitating disease has on populations, and the economy.

Fukuda is a simplified version of the Holmes defintion:https://me-pedia.org/wiki/Holmes_criteria
and the Canadian Consensus Criteria for ME/CFS: https://www.mefmaction.com/images/stories/Overviews/ME-Overview.pdf

The Holmes definition (1988) had more signs and symptoms.

Fukuda (1994) excludes many ME symptoms, which plays into the desires of some to dismiss this disease as of less consequence, relatively easy to recover from, despite info that advises only about 5% recover.

This of course touches on the whole CFS vs. ME topic, which is another complicated, unclear issue, partly perpetuated by overly general, simplified definitions.

 

I think epidemiology is by far and away the number one research priority for ME/CFS however we need to understand what can be achieved, what needs to be achieved and at what cost.

Large scale random sampling of whole populations which involves detailed medical examination of individuals, is both massively expensive and difficult to achieve.

A bit like the apocryphal tourist who stops to ask the way to Dublin and receives the reply "it'd be better not to start from here" we can wish to have epidemiology based solely on our preferred criteria but the reality is that 10s, maybe 100s of 1,000s of patients have a diagnosis that uses older/different criteria. Not only is it impractical to work wholly from 'as new', it is important to understand what those past criteria represent, what patient population is captured by them and how that patient population relates to a that exclusively captured by a preferred criteria.

At present we know very little about the patient population that has been diagnosed with criteria that are likely to capture those who we might agree are 'genuine' ME/CFS patients. Age, age at onset, pattern of illness, level of disability, socioeconomic background and situation, geographic spread - even the much touted gender imbalance is uncertain. Irrespective of criteria fit, all these people who have a diagnosis are in need of responsive health and social services, and at the very least commissioners of those services need good data in order to provide for that need.

If we take the UK as a basis for what might be a way forward -it has largely integrated health system with extensive data - it is possible to describe a potentially useful epidemiological study. The aim would be to enumerate the number of people who have been given formal or informal (GP only) diagnosis of PVS, ME, CFS etc by whatever criteria, and to describe that population by demographics, diagnostic criteria applied, service use etc.

Once this global population had been properly described it would be possible to test, by sampling across demographics, how a preferred diagnosed criteria matched or mismatched historical diagnoses. This would then usefully inform biomedical research as to the significance, or otherwise, of individual patient characteristics. It maybe that the pathology of ME/CFS can be distinguished from other similarly presenting pathologies by the use of symptom based criteria alone, but it might also be the case that age, or gender or ethnicity or environmental exposure or something else, are of equal or even greater significance.

PEM, for example may be the great divide it currently appears to be, or PEM may pale into statistical insignificance when compared to some wholly unexpected characteristic. Without pathophysisiological findings we need to remain sceptical of the usefulness of case criteria to precisely circumscribe the commonality of underlying disease in the patient population. For now the epidemiology of ME/CFS needs to be fairly broadly cast.

Edit to add missing words

 

Research is always going to require a standardised protocol, so to actually get to a lab test CPET or some other measurable provocation is needed to investigate the phenomenon.

Post exertional malaise has always been an accurate description of my experience - 24 to 48 hours after investment of effort I feel utterly crap for a variable number of days. But it's clear that is not a universal experience among patients, and the wide variation would seem to make PEM a somewhat nebulous target: https://www.frontiersin.org/articles/10.3389/fneur.2020.01025/full

If for example PEM is just an unusual response to a normal process, and the chemistry of the response itself is not easily distinguished from other normal processes there may not be anyway to make a meaningful measure from a blood draw. And with the indications that PEM is not a single disease entity but something which has obscure/complex subtypes that add orders of uncertainty to any investigation.

Of course none of those concerns mean PEM shouldn't be researched but we desperately need solid basic data of the type epidemiology can provide. Certainly within the UK context it is exactly what the NIHR should be funding because the lack of the data on the ME/CFS patient population inhibits NHS planning for meeting patient need, an argument that should be made forcefully once the NICE guidelines come out.

 

The original symptom in ME was stated as an abnormal response to exercise. PEM as a concept was introduced by the CDC definitions of CFS which were thought up by people who did not have the patient's interest at heart. One of them was Michael Sharpe and Stephen Strauss was in charge at the CDC and he hated us.

What I mean is that it is not something that was decided after looking at patients it was a way of saying an abnormal response to exercise but leaving it open for a psychological explanation. (Strauss said that patients were B rated people who wanted an A rated lifestyle)

People with ME accepted PEM because it fit with our abnormal response to exercise but now it is being used to describe any increase of symptoms with exercise but that is a normal response in disease.

The things which are unique to us, the immune problems which cause glands to swell or the delay in experiencing symptom increase and the curious way that mental exertion can affect us physically and vice versa are being ignored.

My own personal view is that it is being looked at the wrong way. PEM is something that happens as a result of our disease causing a problem with cellular respiration so we do not have enough available rather than the fatigue with a properly functioning respiration system in other diseases.

Looking at a disease a different way is not unusual in medicine.

 

Given that (it appears ?) that the patient voice is now informing research to a degree that has some significance, it is perhaps more important that priorities sought by patients reflect our expectations.

The point I was trying to make in contrasting epidemiology with (as an example) PEM, is that a properly conducted epidemiological study should produce hard data which would inform service provision, biomedical research and be supportive of advocacy. In contrast, as with much current ME/CFS research investigating PEM would be speculative - it may produce something remarkable, it may produce something useful or it may produce nothing at all. That of course is the nature of scientific inquiry but we need to be clear what our expectations are. If as patients we are prioritising speculative research then we have to own that if the results show a dead end, or just the usual rabbit hole where one study, demands another study, demands a follow up that leads to some interesting but unspectacular answers.

PEM is interesting, yes it looks to be distinctive, but investigating further may show that what looks distinctive is a cloud of interacting phenomena that can't be tied down to any specific biologic process. Of course because it looks to be distinctive it needs be investigated but when it comes to priorities my sense is that what both ME/CFS research and ME/CFS advocacy need right now is some very definitive data on which to build, right now epidemiology seems the best/fastest route to get that.

 

I take your points. However, in my view, we are not starting from 0 with our understanding of this disease. We have good definitions of ME/CFS in the Canadian Consensus Criteria, and the International Consensus Criteria.

The Canadian Consensus Criteria (CCC) with 11 world experts, is superior to the Fukuda definition. The Fukuda definition allows more psychiatric signs and symptoms, and PEM is optional, whereas with the CCC, PEM is required, and this criteria emphasizes more physical disability.

I also note that the 2015 Institute of Medicine, now the National Academy of Medicine criteria requires PEM. This body recognized PEM as the hallmark of ME/CFS: https://www.nap.edu/resource/19012/MECFS_ProposedDiagnosticCriteria.jpg

(The International Consensus Criteria is also superior to Fukuda; I will not comment further here on that criteria:https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2011.02428.x)

The Canadian Consensus Criteria, pages 9 and 10 advises: " Based on the consensus panels' collective extensive clinical experience diagnosing and/or treating more than twenty thousand (20,000) ME/CFS patients, a working clinical case definition, that encompassed the pattern of positive signs and symptoms of ME/CFS was developed."https://www.mefmaction.com/images/stories/Medical/ME-CFS-Consensus-Document.pdf

From the study in large bold print below:

"The findings suggest that both the Canadian and Fukuda et al. case definitions select individuals who are statistically significantly different from psychiatric controls with chronic fatigue, with the Canadian criteria selecting cases with less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurological symptoms."
Comparing the Fukuda et al. Criteria and the Canadian Case Definition for Chronic Fatigue Syndrome
Leonard A. Jason
,
Susan R. Torres-Harding
,
Amber Jurgens
&
Jena Helgerson
Pages 37-52 | Received 07 Jun 2003, Accepted 25 Sep 2003, Published online: 04 Dec 2011

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https://www.tandfonline.com/doi/abs/10.1300/J092v12n01_03


Authors, Mary Dimmock, and Matthew Lazall-Fairman's document Thirty Years of Disdain, page 154 contains a summary comparison of the various ME/CFS criteria:

https://www.dropbox.com/s/bycueauxmh49z4l/Thirty Years of Disdain - Background.pdf?dl=0

One can see from the chart in the above Dimmock, and Lazall-Fairman document that over time, signs and symptoms have been excluded or included in various criteria. The Holmes criteria in 1988, has more signs of infection than the Fukuda definition which was published in 1994.

For decades our community has been saddled with overly broad criteria, which has blurred the outlines of this illness to such an extent it has become indistinct from burn out, depression, and just everyday fatigue etc. In my opinion we must not accept the continued reliance on case definitions that assign pwME to such diagnoses, nor accept token amounts of research funding.