Correspondence with Doctors - Letter in responce to Lynch and Clare

The following is a response to Lynch and Clare and was published
in the "Modern Medicine of Ireland" (July/August 1999 edition).

The Editor
Modern Medicine of Ireland
Eirann Publication Ltd
3-5 Camden Place
Dublin 2
Eire
15th June 1999

Dear Madam,

A response to Lynch and Clare

As an archivist specialising in chronic fatigue syndrome (CFS), I was deeply disappointed to read the review by Lynch and Clare (Modern Medicine of Ireland, May 1999). Indeed, I have great difficulties accepting that Prof. Clare put his name to such a biased and misleading review.

Prof. Clare and I met when I was a postgraduate in London. At that time, there were several physicians, surgeons and psychologists with CFS who were openly talking or writing about their illness. They were all highly intelligent and sensible people, whose disability was certainly not due to excessive inactivity, somatisation, or irrational beliefs. They, and thousands of patients like them, have suffered needless distress because of the widespread ignorance and confusion which surrounds CFS. In this response, I wish to correct some of the errors and misinformation in the article, and to offer Irish doctors a more balanced view of the illness and the literature.

Perhaps the most important point to make is that CFS is an umbrella term for a variety of disorders all characterised by ongoing fatigue¹. For instance, it covers post-viral syndromes, atypical affective and primary sleep disorders, 'burnout', the syndrome linked to organophosphates and other toxins, and various hormonal and nutritional deficiency states. There is also a small subset of patients whose ongoing fatigue may be perpetuated by psychopathology and unhelpful beliefs². It should be noted however, that the majority of people with CFS are no more inactive than patients with multiple sclerosis or arthritis who do not go on to develop CFS. Moreover, there's no evidence supporting a direct link between inactivity and CFS, except where depression plays a significant role. In fact, virtually all the research on this subject has shown that most of these patients have perfectly realistic views of the aetiology; that they do not resort to 'excessive rest' and that after an initial period of trial and error, most cope extremely well^3-8.

It should also be pointed out that the inactivity theory cannot account for phenomena like the daily fluctuations in severity, the worsening of muscle fatigue 24-48 hours after exertion, or common symptoms such as swollen glands, low-grade fevers and intolerance to alcohol⁹. (If lack of activity really caused CFS, alcoholism would be far less common than it is!)

I accept that Lynch and Clare may not have been impressed with 'the attempts to link CFS with viruses'. However, is the evidence supporting the inactivity theory so much more persuasive? The authors cite two studies. The first involved six patients with depression as well as physical and mental fatigue. The second summarised the "observations" on 100 patients with broadly-defined CFS but described views and behaviours usually associated with depression, somatisation or stress. Neither study included an objective measure of inactivity. Conversely, all the studies on strictly defined CFS have shown that these patients report a much wider range of beliefs and coping strategies than those described by Lynch and Clare⁵⁶⁸⁹.

Again, focusing on the evidence, what was the basis for the authors' suggestion that: 'whatever triggers the onset of CFS may not actually perpetuate it'. If this is a serious hypothesis, could they specify when the virus disappears? Six weeks? Six months? And can they explain how inactivity and depression cause the exact same symptoms as the initial infection? The only reference cited is a study on broadly-defined CFS, where the presence of psychiatric disorders almost certainly confounded the results²⁵⁸.

People are entitled to their opinion. However, why did the authors not mention the studies which showed cognitive-behavioural therapy (CBT) and graded exercise to be ineffective for CFS?¹⁰¹¹. Also relevant are the latest data from the first ever trial on CBT. According to Sharpe, the differences between the treated patients and the untreated controls disappeared after several years¹². Indeed, it's worth noting that all the studies which reported a beneficial response were conducted on patients with broadly-defined CFS and all but one included people with psychiatric disorders known to respond to CBT. In the only study which excluded patients with depression, half of the subjects were taking anti-depressants at the time of testing, often at doses not usually tolerated by people with CFS¹³. This study also excluded severely affected patients, compared exercise with a treatment known to be ineffective, and despite the apparent improvements, the fatigue scores after treatment remained relatively high.

On the basis of all the available evidence, one can conclude that CBT and graded exercise are helpful for the subgroup described by the authors, but that the effects are limited and may not last. Indeed, graded exercise is inappropriate for those who do not suffer from phobic avoidance, and could be harmful for patients with ongoing disease^14-23. Alternatives include multidisciplinary programmes featuring gentle activity as tolerated ('pacing'), and supportive counselling or CBT where required⁹²⁴^.

It goes without saying that the presence of psycho-social complications will exacerbate distress and delay recovery. However, I believe that Lynch and Clare exaggerated the influence of psychological factors and thus gave a distorted view of both the illness and the research.

Space does not permit me to challenge all the other misleading statements. However, the following information may help to provide a more accurate view of the literature. Firstly, the article claimed that hypoperfusion in the brainstem had been found by one group of researchers "but not by others". In fact, two groups have assessed brainstem perfusion in patients with strictly-defined CFS, and both reported the abnormality mentioned¹⁶. Secondly, there is evidence of persistent infection and for the involvement of viruses other than Epstein-Barr. For instance, an autopsy on a patient with myalgic encephalomyelitis (a small subgroup of CFS), recovered enteroviral RNA from the brain, heart and skeletal muscle, which was not found in depressed controls¹⁷. The viral persistence theory is also supported by the response to antiviral drugs. For example, one study reported significant improvements in patients with high antibody titers to cytomegalovirus who were treated with ganciclovir¹⁸.

There is also growing evidence of muscle pathology. For instance, researchers have found increasing muscle weakness in patients with myalgic encephalomyelitis which was greatest 24 hours following exercise¹⁵, as well as raised levels of acylcarnitine¹⁹ and other abnormalities²⁰. Moreover, it was unfair not to mention the reports of immune dysfunction²¹²², particularly the increased levels of cytokines which may be linked with the low grade fevers and flu-like malaise²³. All these findings were documented in CFS patients long after the initial illness and most are difficult to explain in terms of inactivity or maladaptive beliefs.

As for the notion that a belief in a physical cause is "one of the strongest predictors of poor outcome", this is supported by one seriously flawed study but at odds with at least three others ⁴^,²⁵²⁶.

Finally, I would like to challenge some of the authors' comments on the psychopathology in this patient population. I've reviewed all the published research and calculated that the prevalence of major depression in strictly-defined CFS is similar to the estimates documented for cancer and MS²⁴²⁷²⁸. The higher rates quoted in some articles can be attributed to the use of broad criteria known to select a more heterogeneous population⁸⁹. As for somatisation, the reliance on a list of common symptoms makes this a difficult condition to diagnose, but the prevalence in patients with CFS is still considered too low²⁹.

Incidentally, the ongoing confusion between the fatigue linked to psychiatric morbidity and the exhaustion associated with CFS has led to the search for a less ambiguous term. The American Surgeon General hopes to announce the new name next year.

Conclusion

I do not know why some mental health professionals appear to lose their objectivity when considering CFS. The publication of biased and misleading reviews essentially disempowers doctors and makes a mockery of evidence-based medicine. Interestingly, the authors of such articles often complain that their patients' unhelpful beliefs are "reinforced" by "poorly informed media discussion and coverage". That's a perfectly fair point, as long as one acknowledges that in relation to CFS, the same flaws can be found in the medical press. Indeed, it may be argued that the "abnormal illness behaviour in patients has an equal and opposite phenomenon of abnormal illness perception in doctors"³⁰.

I accept that theories about human behaviour and adherence to the scientific method encourage generalisation, a selective blindness to individual differences and oversimplification. However, reductionism has its drawbacks. The suggestion that most cases of CFS are the result of excessive inactivity, depression and irrational beliefs may seem perfectly plausible, but if doctors don't realise that this only applies to a small subgroup, they may end up giving many patients totally inappropriate advice.

Feeling misunderstood, and having failed to improve on treatments like CBT, some patients will look for help elsewhere. This is regrettable, unnecessary and potentially dangerous. Isn't it better to acknowledge the complexity of CFS, to consider all points of view, and admit to our patients that there's much we don't yet know? That wouldn't prevent us from offering treatments or from providing emotional support. However, it would allow us to operate at the same level of knowledge as our patients, and some may appreciate our honesty!

Yours faithfully,

Ellen Goudsmit (Dr.)

References

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