Submission on 2nd Draft of "Australian Guidelines on CFS" Jill Booth, BSc

Firstly, I would like to thank the authors for asking for further comments on the Guidelines. It seems substantial changes have been made since the first draft and this I find pleasing.

This second draft appears more practical and useful for the target audience — GPs, and other allied health professionals engaged in treating and managing CFS. It acknowledges that symptoms are "currently believed to be due to disturbed brain function" and that there is currently a lack of understanding of underlying pathophysiology. This approach I feel is much more useful for the practitioner and patient alike compared with the psychobiological models presented in the previous draft.

GENERAL COMMENTS

I am heartened to read that the reality, seriousness, suffering and disability of CFS have been well compared with the suffering of MS and RA — this should help people realise the extent of the disability of CFS, which is often not apparent at the time of consultation . An omission that I'd like to suggest is an explanation of the continuim of illness — from those who continue to be able to struggle on with working/studying to those who are more severe and who are unable to work because of the illness. This is similar to MS and RA. Also the fluctuation in symptoms, which is characteristic of CFS needs more emphasis.

I also feel that the interested GP and their patients should be directed to further information. There are many good books on the market (and many bad) and patients need to be warned off those proclaiming miracle "cures". My top 3 books are written by physicians and I would recommend to patients and GPs alike , namely:

Also GPs should be made aware that there is the Journal of Chronic Fatigue Syndrome published by the Howarth Press.

Another source of current information is to be found on the internet. Patients are going to look information up and it is best to keep abreast of reputable sites and even recommend them in order that patients aren't seduced by snake oil salesmen. Once again caution needs to emphasised. Informative well documented information can be found at

SPECIFIC COMMENTS

I now want to go into further detail about various specific problems I can still see with the Guidelines — either where ambiguity arises, where there are omissions or where information is not substantiated well.

Page 6 — Examination
It says there are no abnormal physical findings. But
- Note should be made that there is a characteristic pallor if patient is in relapse.
- Note exudative pharangitis is often present
- orthostatic intolerance can be elicited in many patients

Page 7 - Specialist referral
I agree that in most cases, a general practitioner should be able to make the diagnosis — there is little else that can cause such an abrupt change in function and combined symptom complex. Pg 19 however contradicts this by saying "While physicians working in tertiary referral centres may encounter patients with CFS quite commonly, primary care doctors will not" This is ambiguous and needs clarifying/deleting.

Page 8 — Management
I do not understand why the first sentence is included. Whilst I agree that some prolonged fatigue states do resolve spontaneously the sentence is redundant in a discussion about CFS management where 6 months has already elapsed before diagnosis. Whilst I agree that Drs should not reject patients or trivialise a patients suffering I do not see this as a possible cause of perpetuated ill health. The sentence beginning with " Conversely ä . " is best ended with a fullstop after the word " alienation."

I see the emphasis on rehabilitation as problematic because as far as I'm aware we are not at all clear about what we are rehabilitating people from. I am aware of the "vicious cycle of inactivity" and agree that this needs explaining to patients. I am also aware that at times all patients can possibly do is rest and pushing beyond their limits is very counter-productive. I would suggest patients do what they can, when they can.

Ref: Is Physical Deconditioning a perpetuating factor in Chronic Fatigue Syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychological Medicine — 2001, 31, 107-114 January 2001 Bazelmans E, Bleijenberg G et al

Whilst it seems obvious to implement strategies directed at minimising impediments to recovery I have not read anywhere in any research just what the impediments to recovery are. If we knew this we would be a lot further down the track and people would be recovering. I agree that managing sleep is very important, managing depression is very important and managing social isolation is very important, but I fail to understand how to manage loss of aerobic fitness. If patients can improve symptoms of the illness with increasing aerobic fitness , then to my mind they do not have CFS. Also I fail to understand how Drs are to impart "a clear understanding of the illness". Whilst I agree that notions of occult infection, environmental pollutants, electromagnetic fields causing the illness, do need to be dispelled I also think patients should be told the truth ie that we do not know what specifically is causing the illness . Patients with other illnesses are told this everyday. I agree that Drs should avoid attributions that are unwarranted eg "malingering" and "mere depression" . I do not think however that we can say that "immune dysfunction" is wrong.

Ref: "Chronic Fatigue Syndome: Evidence Supporting the Hypothesis of a Behaviorally-Activated Neuromodulator of Fatigue" Hurwitz, Brownley, Fletcher,Klimas. Jof CFS Vol 6 , 1999 No 2

Ref: Detection of Immunologically Significant Factors For Chronic Fatigue Syndrome Using Neural Network Classifiers. Clin Diag Lab Immunol 2001 May;8 (3):658-662. Hassan SJ, Gause W, Natelson B

Ref: Comparative Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of Patients with Chronic Fatigue Syndrome. Fletcher MA, Maher K, Patarca-Montero R, Klimas N. Jof CFS Vol 7, Part 3&4 2000 pp 65-75

Ref:Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors. Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG. Appl Neuropsychol. 2001;8(1):51-64. PMID: 11388124

Ref:A 37kDa 2-5A binding protein as a potential biochemical marker for Chronic Fatigue Syndrome. De Meirleir K, Bisbal C, Campine I et al The American Journal of Medicine , Vol 108, Issue 2 pg 99-105

Ref: Neurological Dysfunction in Chronic Fatigue Syndrome, Chaudhuri A, Behan PO, Jof CFS Vol 6 1999, No 3&4 pp51-68

I don't see any problem with telling patients that they have an immunologically mediated brain dysfunction — that is what my doctor tells me I have. An explanation such as this is perfectly adequate and is not beating about the bush. I do agree that a broad perspective of the disability needs to be recognised.

I would like to see the multicentred , well controlled trail results where it has been shown that graded exercise has been shown to be safe and has improved aerobic capacity and functional status in CFS patients. It is my understanding that in studies of this sort, that many definitions of CFS/ME were used and until such time as I see well controlled multicentred trials all using the CDC criteria and all showing the same comparable efficacy , The literature does not suggest graded exercise as a form of treatment applicable for all patients with CFS. To state that graded exercise is safe in all this patient group is not proven, yet it is proven that some patients do have evidence of ongoing muscle degradation. I think therefore that much caution needs heeding when suggesting exercise as therapy.

Ref: Patient education to encourage graded exercise in chronic fatigue syndrome.Trial has too many shortcomings. Chaudhuri A. BMJ 2001 Jun 23;322(7301):1545-6 PMID: 11439997

Worsening of symptoms after exertion, and delayed recovery are characteristics of the illness (ie part of the definition) and Drs and patients need to understand this. This ebb and flow are what define the illness and are not under the patients control or are they any form of illness behavior. If patients can undertake regular activity then yes it needs to be encouraged, but many are far too ill to and this needs acknowledging .

Ref: Chronic fatigue syndrome: new insights and old ignorance. Evengard B, Schacterle RS, Komaroff AL. J Intern Med. 1999 Nov;246(5):455-69. Review.PMID: 10583715

Sleep
The section on sleep is good but I think it would help GPs to have more specific recommendations from experienced CFS clinicians. This is where the 3 books mentioned earlier will be of help as well as the following recent papers.

*Ref: Toward optimal health: the experts discuss chronic fatigue syndrome: interview by Jodi Godfrey Meisler.Klimas N, Wallace M. J Womens Health Gend Based Med. 2000 Jun;9(5):477-82. PMID: 10883938 To obtain the article call the publisher at 914 834 3100 (Note: USA)

Ref: The biology of chronic fatigue syndrome. Komaroff AL. Am J Med. 2000 Feb;108(2):169-71. PMID: 11126311

Ref: The symptoms of chronic fatigue syndrome are related to abnormal ion channel function. Chaudhuri A, Watson WS, Pearn J, Behan PO. Med Hypotheses. 2000 Jan;54(1):59-63. PMID: 10790725

For example — the combination of Klonopin (1mg) plus low dose Tricyclic antidepressants eg 10mg Amitriptyline, or 5-20mg Sinequan Exilir ." Klonopin puts you to sleep, Amitrip keeps you there" (Lapp) Other good sleep medications include Neurontin ,an anticonvulsant, and Ambien. [Refer * reference above for full discussion]

Symptomatic Drug Treatment
I commend the stress placed on advising Drs to begin with low doses of medications given the increased susceptibility of people with CFS. I also commend the suggestion of N=1 trial What is omitted from and is needed in this section is suggestions for the treatment of pain, cognition, and energy. Information from key clinicians once again would be of value here. The reference below is once again ideal.

Ref: Toward optimal health: the experts discuss chronic fatigue syndrome: interview by Jodi Godfrey Meisler.Klimas N, Wallace M. J Womens Health Gend Based Med. 2000 Jun;9(5):477-82. PMID: 10883938 To obtain the article call the publisher at 914 834 3100 (Note: USA)

Summary:
Pain — Neurontin, Long Acting Narcotics. Massage, Acupuncture, Stretching
Cognition —Some patients helped by Ritalin, Wellbutrin, Provigil
Energy — B12 injections up to 5,000mg/day

Page 12 - Psychological and Social Support
This section is good, perhaps more recognition of cognitive difficulties needs discussion. The discussion of the good and bad points of support groups is very sensible advice.

Page 13 - Special Considerations in Children and Adolescents
This section on the whole is good although I think it is necessary to acknowledge that not all children recover. The follow up study below by Bell et al showed 37.1% considered themselves resolved of illness, 42.9% considered themselves well but not resolved, 11.4% considered themselves chronically ill and 8.6% considered themselves more ill than during the early years of the illness. Whilst on the whole the prognosis is good it has to be of concern that 20% remained very unwell , 13 years after onset.

Ref:Thirteen-Year Follow-up of Children and Adolescents with Chronic Fatigue Syndrome . Bell D et al S Pediatrics Vol 107 No5 May 2001 pp. 994-998

Again in this section årehabilitation as treatment' is somewhat over emphasised.

Page 21 - What is the outcome of Fatigue States
One note on suicide : I think clinicians may have a different view of the rate of suicide in CFS. I have known 4. I think this is a very understudied area.
Page 22 — the last paragraph. Whenever outcome studies are analysed I wonder that maybe the patient understands the illness to be purely physical in nature because 1) it is and 2) their doctors have told them so.

Page 23 - What is known about the Pathophysiology of CFS?
Research has shown that the last 2 suggestions in the box are not correct and these need to be deleted

a neuropsychiatric disorder with clinical and neurobiological aspects suggesting a link to depressive disorders (Wessely 1993)

Ref: Psychiatric Correlates in Chronic Fatigue Syndrome, Ann Epidemiol Axe E, Satz P. 2000 Oct 1;10 (7):458- PMID: 11018367

psychologically determined response to infection or other stimuli occurring in "vulnerable" individuals (Imboden et al 1961; Abbey 1993)

Ref: Chronic fatigue syndrome: new insights and old ignorance. Evengard B, Schacterle RS, Komaroff AL. J Intern Med. 1999 Nov;246(5):455-69. Review.PMID: 10583715

Other hypotheses that require addition to the list include:

Page 24 - Natural History Box
The 3rd and 4th points need deleting based on references above.