Heterogeneity of ‘CFS/ME’

The Dangers of Failure to Subgroup

 

 

January 2002: Quotations from

 ‘A Report of the CFS/ME Working Group to the Chief Medical Officer’[1]

The CMO assembled the Working Group to report on CFS/ME. Many correspondents with the Group noted that the term CFS/ME covered subgroups of patients who might have different aetiology, symptom complexes, or response to various treatments. The members of the Key Group, the Children’s Group, and the Reference Group also reflected this perspective to varying degrees. 1.4.1 Definitions and Terminology, page 5

The Working Group accepts that some patients’ presentation and symptoms align more closely to the original clinical description of ME[2] than to the current definition of CFS by the US Centers for Disease Control and Prevention[3].                          3.4.1 Subgroups, page 25

Some patients with CFS/ME might not respond, or might even respond adversely, to certain treatments found effective in other patients. …  In view of concerns raised over patients’ experience, the question of whether differential treatment response represents some distinct difference in disease merits carefully planned research.

                                                                               4.4.1.1 Response to treatment, pages 44-45

 

 

The CMO’s Report thus highlights the heterogeneous nature of ‘CFS/ME’ at a number of points, whilst highlighting the need for resolution of this issue as a “key message”:

 “One highly heterogeneous disease might exist that encompasses CFS/ME or several related pathophysiological entities may exist; these distinct hypotheses should be studied.[4]

The Report also acknowledges:

“These possibilities complicate the consideration of aetiology and pathogenesis, as they do other aspects of the condition.”[5]

It is therefore unsurprising to find varied needs, degrees of disability and confounding conditions among patients subsumed under the broad diagnostic banner of ‘chronic fatigue syndrome’ (CFS) as currently defined in the UK. However, at present, a ‘one size fits all’ approach to management and treatment has been adopted. Broad fatigue criteria have also confounded the conduct of research.

Problems caused by the use of broad ‘fatigue’ definitions – the Danger to Patients

A focus on ‘fatigue’ and the failure to distinguish between chronic fatigue and strictly defined chronic fatigue syndrome have resulted in a mixed cohort of patients being viewed collectively as ‘chronic fatigue’ sufferers. Furthermore, the assumption is that this ‘fatigue’ does not have a medical root. This broad approach must be reassessed, as it may place a considerable number of patients at increased risk of iatrogenic harm.

________________________

Coupled with a tendency to disregard other symptoms, the use of the somewhat inaccurate term ‘fatigue’[6] and the adoption of broad ‘fatigue’ definitions have contributed to a fundamental misunderstanding about the nature of the condition. One U.S. doctor, with over a decade’s experience of seeing patients and following the relevant literature closely, has summed up the problem. Referring to those who conflate ‘chronic fatigue’ and ‘chronic fatigue syndrome’, he observes:

“They often fail to distinguish between ‘chronic fatigue’ and ‘chronic fatigue syndrome’. The former is a fairly common symptom in medical clinics that does have a high linkage to already-present psychological problems. The latter, as we know, is a fairly specific medical condition with an unfortunate name. Their sloppiness has led to all kinds of trouble and misunderstanding.” [7]

To quote an example, this conflation is explicit in the following piece on ‘Epidemiology of CFS’. Referring to the findings of a survey concerning the incidence of fatigue among population at large, it is reported that:

“18% had experienced substantial fatigue for six months or longer. Fatigue, however, was ‘normally’ distributed - i.e. the world could not be divided into those with chronic fatigue (the ill group) and those without (the well). What we were looking at was more like blood pressure: we all have it, some have higher levels than others, and a few have such high levels that something has to be done about it, but the division between normal and high blood pressure is arbitrary”. [8]

This author – in common with many - clearly fails to distinguish the experience of ‘chronic fatigue’ alone, and the condition which has come to be known as ‘chronic fatigue syndrome’. This is not a matter of semantics. It is explicitly stated here that the only difference between ‘CFS’ patients and other people lies in the amount of fatigue experienced. This is profoundly inappropriate - not least because, while everyone experiences fatigue at some time, no normal healthy person experiences the sort of malaise which this illness produces. Yet these misguided perspectives underpin much official policy on management and treatment.

In this context, it is noteworthy that the World Health Organisation classifies ME and CFS as neurological in the International Classification of Diseases. Chronic fatigue, on the other hand, is listed as a mental and behavioural disorder alongside ‘neurasthenia’.

The conflation of ME and strictly defined CFS with ‘chronic fatigue’ has led to the endorsement of behavioural interventions such as exercise as appropriate to all patients presently diagnosed with CFS, despite strong indications that exercise is harmful to some. This endorsement of exercise is based on a fatigue perspective, coupled with speculation regarding the possible role of de-conditioning. This is misguided, in two respects. Firstly, this perspective fails to take account of the distinctive clinical presentation of ME/strictly defined CFS. Furthermore, the speculation that patients are de-conditioned as a result of prolonged inactivity lacks an evidence base: indeed, evidence exists which would challenge this.[9]

It should be noted that research studies on behavioural interventions - i.e. graded exercise and cognitive behavioural therapy aimed at encouraging such exercise - which report beneficial outcomes have selected participants using broad fatigue criteria. Most commonly the so-called ‘Oxford criteria’[10] are used. These are even more broadly inclusive of a heterogeneous population than the definition of CFS by the US Centers for Disease Control and Prevention previously referred to.[11] Indeed, one of the co-authors of the ‘Oxford’ criteria has described them as follows:

 “British investigators have put forward an alternative, less strict, operational definition which is essentially chronic fatigue in the absence of neurological signs [but] with psychiatric symptoms as common associated features.” [12]

At the same time, a considerable body of evidence exists which challenges the wisdom of exercise for patients with ME/strictly defined CFS. For example, a substantial number of research studies indicate an abnormal response to exercise, including some which demonstrate the presence of physiological characteristics which would contra-indicate exercise – and in particular aerobic exercise.[13]

As they stand, current perspectives and practice may place a considerable number of patients at increased risk of iatrogenic harm by not affording due care and attention to:

§                The internationally documented contra-indications to exercise applicable to some patients presently subsumed under the umbrella diagnosis ‘chronic fatigue syndrome’.

§                 Detailed assessment of the clinical presentation of individual patients in order to make a distinction between (i) patients whose fundamental problem is chronic fatigue without a medical root and (ii) ME/strictly defined CFS  patients.

§                The clearly articulated voice of patients concerning what does and what does not help, as contained in evidence from patient surveys carried out by several ME Charities.[14]

 

Furthermore, it should be noted that research suggests that even within more a more clearly defined patient population there are subgroups.  Identifying these subsets is vital if appropriate treatments are to be developed and properly targeted. For example, the research work conducted by Dr A. Martin Lerner - summaries of which are included as part of this submission[15] - shows clearly that some patients respond well to anti-viral therapy, but that this must be specifically directed depending on the type of virus present.[16] So, the lack of appropriate investigation to identify specific abnormalities means that subsets of patients who are likely to benefit from specific immunological therapies are not identified, and patients are denied the chance to improve.

The Urgent Need for Improvements in Diagnostic Practice

These flaws and omissions arise from the fact that current diagnostic procedures for CFS in the UK - whether for research purposes or in clinical practice – not only lack specificity but also hold the potential for danger for certain patients.  This is unacceptable.

Published early in 2002, the CMO’s Report acknowledges that appropriate diagnostic criteria were then lacking:

 “Current diagnostic criteria (sic.) are useful only for research purposes, and no clinically recognised set of diagnostic criteria exists.”[17]

However, a paper entitled Clinical Working Case Definition, Diagnostic and Treatment Protocols”[18] was published a year later, in February 2003. Arising from a Canadian initiative, this publication reflects the expertise of an international panel of clinicians and researchers. 

“Based on the consensus panel’s collective extensive clinical experience diagnosing and/or treating more than twenty thousand (20,000) ME/CFS[19] patients, a working clinical case definition, that encompassed the pattern of positive signs and symptoms of ME/CFS, was developed.” [20]    

In accordance with its aim, this protocol aids the selection of a much more homogeneous group:

 “The objective was to provide a flexible conceptual framework for clinical diagnoses that would be inclusive enough to be useful to clinicians who are dealing with the unique symptomatic expression of individual patients and the unique context within which their illness arises. The panel felt there was a need for the criteria to encompass more symptoms in order to reflect ME/CFS as a distinct entity and distinguish it from other clinical entities that have overlapping symptoms. As fatigue is an integral part of many illnesses, the panel concurred that more of the prominent symptoms should be compulsory.”[21]

Adoption of these diagnostic criteria in the UK would clarify the nature of ‘ME/CFS’ amongst health professionals. With clear diagnostic criteria and treatment protocols now published, medical practitioners are placed in a precarious legal and ethical position if they choose not to take account of this guidance when prescribing treatments and management strategies for patients with ME.  This is particularly relevant in relation to graded exercise, currently being prescribed across the UK, which may well result in avoidable (and possibly irreversible) harm to some patients subsumed under the unnecessarily broad diagnostic label presently in use.

The implementation of the published clinical criteria within health care and social policy would establish a means for the clear diagnosis of ‘ME/CFS’ – a benefit for both patients and clinicians. It would also have a significant impact on the progress of research, many of whose problems so far have emanated from some researchers’ use of very broad selection criteria. The adoption of an agreed set of diagnostic criteria would ensure that researchers refine their selection criteria from among a clearly defined group of patients, a practice which is surely standard in other medical conditions.

 

 

Key Messages

§   The term ME is rarely used now in medical circles, and most doctors are unaware of the unique and distinctive presentation of this illness. Instead, people presenting with the clinical features of ME are given a diagnostic label of ‘Chronic Fatigue Syndrome’ (CFS).

§   As currently practiced CFS is a broad category which has caused confusion in the medical perception of patients with ME and muddied the waters in research and clinical practice. In particular, CFS is widely misperceived as synonymous with chronic fatigue occurring in the absence of a medical basis.

§   Agreement on suitable clinical criteria is a prerequisite for the progress of scientific research. Such guidelines were published three years ago, using a strict definition of CFS, by an expert group of international clinicians and researchers. These guidelines have not yet been endorsed in theUK.

§  Clearly identifying the patient population and distinguishing subsets is vital if appropriate treatments are to be properly targeted, and if patients are to be protected from potentially harmful interventions.

 

 

Recommended Further Reading

Jason, LA et al. Chronic Fatigue Syndrome: The Need for Subtypes Neuropsychology Review, Volume 15, No.1, March 2005, pages 29-58.

Carruthers, BM and van de Sande, MI Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners (an overview of the Canadian Consensus document). ISBN 0-9739335-0-X

 

scotme@ntlworld.com

Submission to Gibson Inquiry January 2006



[1] A Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an Independent Working Group. London: Department of Health, 2002.

[2] Ramsay M. Myalgic Encephalomyelitis and Postviral Fatigue States – the saga of Royal Free disease. London: Gower Medical Publishing, for the ME Association, 1988.

[3] Fukuda K, Straus S, Hickie I, et al. The Chronic fatigue syndrome: A Comprehensive Approach to Its Definition and Study. Annals of lnternal Medicine 1994; 121: 953-59.

[4] A Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an Independent Working Group. London: Department of Health, 2002. Chapter 3: Nature and impact of CFS/ME,  page 19.

[5] ibid. 3.3 Aetiology, pathogenesis, and disease associations, page 21.

[6] Patients may act as though tired, and at times may sleep much more that would normally be expected, but the malaise experienced is not fatigue in the normal sense of the word.

[7] Dr Alan Gurwitt, a child psychiatrist in the US,  as posted on http://www.immunesupport.com 23rd January 2002.

[8] Contributed by S Wessely to ‘A Research Portfolio on Chronic Fatigue’, edited by Robin Fox for the Linbury Trust; published by the Royal Society of Medicine Press 1998. Note that the title of this publication clearly sees the phenomenon concerned as simple ‘chronic fatigue’. The survey referred to involved a canvas of 15,000 people registered at six different general practices. The above quote is from page 2.

[9] Some examples of such research are contained in the document ‘Is Graded Exercise Safe for People with ME?, which forms part of ScotME’s submission to the Inquiry. The document ‘Which Interventions are Helpful to Patients with ‘CFS/ME’? :  A Review of the Evidence’ (submitted to the inquiry by Cross Party Scottish Parliamentary Group on ME) also provides examples of evidence indicating that patients’ illness presentation cannot be explained by deconditioning.

[10] Sharpe M, Archard L, Banatvala J. A report: chronic fatigue syndrome: guidelines for research. Journal of the Royal Society of Medicine 1991; 84: 118 – 21.

[11] See the second of the opening quotations of this document,  referenced at footnote 3.

[12] David AS. Postviral syndrome and psychiatry British Medical Bulletin 1991; 47:4:966-988.

[13] Again, some examples of such research are contained in the document ‘Is Graded Exercise Safe for People with ME?, which forms part of Scot ME’s submission to the Inquiry.

[14] See, the document ‘Which Interventions are Helpful to Patients with ‘CFS/ME’? :  A Review of the Evidence’ (submitted to the inquiry by Cross Party Scottish Parliamentary Group on ME), which provides summary coverage on this issue.

[15] See ‘Human Tragedy and the Heart of the Matter’.

12 See,  for example research studies Nos.7 and 8 (pages 4-5) as featured in ‘Human Tragedy and the Heart of the Matter’.

[17] A Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an Independent Working Group. London: Department of Health, 2002. Para 4.2.1.1 Diagnostic criteria,  page 36.

[18] Carruthers B. et al. Myalgic Encephalomyelitis/ Chronic fatigue syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic fatigue syndrome, Vol. 11 (1) 2003, pages 7-115. The full paper is available to view at: http://www.mefmaction.net/documents/journal.pdf

[19] ‘ME/CFS’ is the term used throughout this protocol.

[20] ibid. p9-10.

[21] ibid. p10.