This is always a contentious condition which invariably inspires heated debate. Here we can look at the evidence to try to achieve a balanced appraisal. This chapter will contain the following sections.
- Abuse and Intimidation of Researchers
- Further Resources
- Site Index
In 1955, the Royal Free Hospital Teaching Group in London, which had a staff of about 3,500 people, experienced an obscure epidemic which affected more than 300 staff.1Epidemiological aspects of an outbreak of encephalomyelitis at the Royal Free Hospital More than half of the cases occurred in July and August that year. The condition was called encephalomyelitis and there was evidence of infection with enlargement of lymph glands, liver and spleen, although I see no evidence of encephalitis, other than the lethargy that accompanied it. The term myalgic encephalitis was coined.
This condition has been variously known as myalgic encephalitis or ME, post viral fatigue syndrome, chronic fatigue and immune dysfunction, and “yuppie flu”. It may occur simultaneously with fibromyalgia. The term myalgic encephalitis is commonly used but is inappropriate. Myalgic suggests a disease of muscle and encephalitis means inflammation of the brain. Muscles are weak and possibly wasted from lack of use but there is no evidence of inflammation of the brain. Therefore, the term ME should be avoided. The term chronic fatigue syndrome (CFS) is currently preferred in the medical world as it is neither pejorative, nor does it imply spurious cause.
It is classified as Post Viral Fatigue Syndrome (PVFS) in the World Health Organisation (WHO) International Classification of Diseases (ICD) and listed as sub-category at G93.3 under chapter G93, other disorders of the brain.
The aetiology or cause of this condition remains unknown although there are a number of lines of inquiry. It may follow a viral infection, especially with a group called enteroviruses.2Aetiology and pathogenesis of chronic fatigue syndrome These tend to be viruses that infect the gut. The concept of post-viral fatigue after influenza and infectious mononucleosis (glandular fever) is well recognised but it usually lasts for weeks rather than months or years. Long COVID may have a certain amount in common. More about this can be found at COVID-19. What You Need to Know. Raised levels of antibodies to certain viruses have been found but this does not prove a cause.
There is no evidence of dysfunction of the immune system although there are some interesting features.3Immunological aspects of chronic fatigue syndrome Do not assume too much from this. Care should be taken in interpretation.4Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome They seem to be more marked in more severe cases.5Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. However, there is nowhere near enough evidence of an immune aetiology to justify trials of modulators of the immune system in treatment.
Potential risk factors are uncertain. A sedentary childhood may increase risk compared to an active one. Emotional and behavioural problems in adolescents may also be weakly predictive. It would be unwise to read too much into this but it would seem that the personality of most sufferers before they have the disease is not unusually neurotic. Therefore it would be unwise to dismiss the disease as purely hysterical. However, those with the condition do seem to have certain traits.
Many will empathise with the late Dr Michael O’Donnell’s definition in his Sceptic’s Medical Dictionary. He says that it is a condition in which the sufferer is far too tired and lethargic to do anything except to argue most vehemently with anyone who suggests that the condition may have a psychological component. The self-diagnosed “ME” is dreaded by doctors and difficult to manage.
The true prevalence is difficult to assess as criteria for diagnosis are not evenly applied. According to a review from 2010, the estimated worldwide prevalence of CFS is between 0.4% and 1%.6Chronic fatigue syndrome/myalgic encephalomyelitis: an update The disease predominantly affects young adults, with a peak age of onset of between 20 and 40 years. The female to male ratio is 6:1. The duration of illness usually ranges from 3 to 9 years although recovery is often incomplete. It affects all racial-ethnic groups and is seen in all socioeconomic strata. It rarely starts in children or after 65 years old, although the disease in children is well described.
Epidemics have been reported at times and this has provoked much debate as to whether it represents an infectious aetiology or an outbreak of hysteria. Both are possible interpretations.6Chronic fatigue syndrome/myalgic encephalomyelitis: an update
A prevalence of 0.4% to 1% would mean that an average general practice of 10,000 patients would expect to have between 40 and 100 sufferers, which I think seems rather high. My personal experience with a list size of over 15,000 was 2 or 3 cases, not 60 to 150. There are thought to be around 2.5 million suffers in the USA and 250,000 in Great Britain. This would suggest roughly twice the prevalence in the USA. A total of 250,000 suffers in the UK would suggest a prevalence closer to 0.4% than 1%.
Specific criteria should be used to make the diagnosis and the ones most often used are those of the American Centers for Control and Prevention.7Institute of Medicine (USA) diagnostic criteria for CFS 2015 The major diagnostic feature is unexplained, persistent fatigue that is not due to ongoing exertion. It is not substantially relieved by rest. It is of new onset (not lifelong) and results in a significant reduction in previous levels of activity. In addition, four or more of eight other symptoms are present for six months or more. There are a number of other conditions that should be considered and again they will not be discussed although they do include psychiatric illness as a cause of depression and anxiety. To a considerable extent, this is a diagnosis based on exclusion of other conditions.
There is no specific diagnostic test, either laboratory or imaging, and so investigations are to exclude other causes. One possibility is multiple sclerosis which may present with fatigue. I once had a patient who was diagnosed as having ME and MS, but I suspect that the chronic fatigue was really the first sign of multiple sclerosis before the other neurological features appeared.
NICE says that features that suggest the diagnosis include:8NICE Guidance CG53 August 2007
- Fatigue gets worse after even mild exercise such as a short walk
- Sleep problems
- Pain in the muscles or joints
- Sore throat or sore glands that although they are not swollen
- Problems thinking, remembering, concentrating or planning
- Flu-like symptoms
- Feeling dizzy or sick or having palpitations with an irregular or fast heartbeat
- Exercising or concentrating on something makes symptoms worse.
NICE says that if no alternative explanation can be found, the diagnosis should be considered after four months in adults or three months in children or young people.
There is evidence-based management of the condition, but it is often difficult to get the patient to accept this. They often prefer injections or CAM treatments that have not been proved to be of any benefit.9Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States This seems to be part of the “ME personality” but perhaps they are just desperate for something with more to promise than the evidence-based treatment seems to offer. The evidence base is for a slow and steady behavioural approach rather than high technology interventions.
A systematic review from the York Centre for Reviews and Dissemination found 70 studies that met the inclusion criteria.10Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis Studies on behavioural, immunological, pharmacological and complementary therapies, nutritional supplements and miscellaneous other interventions were identified. Graded exercise therapy and cognitive behaviour therapy appeared to reduce symptoms and improve function based on evidence from randomised controlled trials. For most other interventions, evidence of effectiveness was inconclusive and some interventions were associated with significant adverse effects. The authors noted that the quality of research in recent years appears to be much better than before.
The basis of treatment has to be graded exercise, both mental and physical. If a fit and healthy person is put to bed for a fortnight, there will be loss of muscle power and muscle mass. There will be loss of joint position sense and balance. Bone is lost. Blood pressure drops on standing. There is loss of the natural daily rhythm of life including waking and sleeping and there will be depression. This makes me wonder if the condition is just a post-viral fatigue that has become chronic (that means prolonged, not severe) as the person has not had the drive to push back to fitness. However, there is no evidence to support this. Anyone who has been ill and inactive for a while has to build up physical fitness slowly but surely. There is mental fatigue too. The principle of “use it or lose it” applies just as much to the mind and mental stamina has to be built up on similar principles. It is important to break the vicious cycle of exercise avoidance and further deterioration.11A brief review of functional disturbances and potential therapy Exercise per se does not appear to improve mental function. Cognitive and behavioural therapy (CBT) is also of proven value.
Graded exercise means gradual building up. If a person who has been inactive for years decides to do a 5 miles run the following day, this is doomed to failure. Start with a short, leisurely walk. Then build up distance and pace. If attempts at exercise seem to leave the person too exhausted over the next few days so that they have been counterproductive, the answer is to step back to a less ambitious target and to build up slowly again. Do not give up. Mental exercise may start with some light reading, perhaps followed by crossword or other puzzles and games. Again, it is graded exercise. In November 2020, NICE brought out new guidelines to be updated in 2021.12Guideline 5 Myalgic encephalomyelitis (or 6 encephalopathy)/chronic fatigue syndrome: 7 diagnosis and management. They suggested that graded exercise therapy should not be followed too rigorously and that it can be counterproductive. I think it is necessary to tailor the management to the patient.
It is not uncommon to find that sufferers from CFS have had major depression in the past and there may well be features of depression in the illness. If there is depression, it is important to treat it. In the absence of depression the value of antidepressants is dubious.13Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome
The Cochrane organisation has reviewed several aspect of management. An updated review in 2011 gave affirmation of the value of graded exercise.14Exercise therapy for chronic fatigue syndrome Cognitive and behavioural therapy has received approval.15Cognitive behaviour therapy for chronic fatigue syndrome in adults A review of Chinese herbal medicine for the condition found that the quality of studies was too poor to draw a conclusion but this review has been withdrawn whilst it is updated.
If the person is in employment, a positive return to work is to be encouraged. Becoming an invalid is to be avoided. The prognosis in children and adolescents appears to be as good as in adults if not better. The prognosis is poor when there is resistance to accepting the active management programme, poor motivation for adherence to treatment or secondary gains from illness.16Predictors of response to treatment for chronic fatigue syndrome. For those who accept multidisciplinary treatment, the gains are much better than in those who are, in effect, untreated. For those who accept therapy the outcome is good but there is not usually a full and complete recovery.
- Chronic fatigue syndrome is a real and debilitating condition although the patient usually looks remarkably well.
- It is essential to use objective criteria such as the ones given by NICE to make the diagnosis. There are no classic symptoms or signs.
- Investigations aim at excluding other causes, and there are many. There is no laboratory test for CFS.
- A firm and positive approach is essential to engage the patient in a programme for recovery. This should be evidence-based, not allowing the patient to meander into the world or unproven and useless remedies.
- The basis of management is graded physical and mental exercise.
- Cognitive and behavioural therapy is of proven value and helps the patient to understand the disease and work appropriately to overcome it.
- Drug therapy is of limited value although there may be associated depression and this does require treatment.
- A positive approach to work or education is required to improve prognosis.
- If the patient complies, the prognosis is good although full and complete recovery is unusual.
Abuse and Intimidation of Researchers
It has been reported that the Cochrane Collaboration has, at least temporarily, withdrawn a review of the management of CFS due to pressure from “activists”.17Science journal to withdraw chronic fatigue review amid patient activist complaints This has caused considerable concern from scientists who see it as a great setback for science that it should defer to the “politically correct.” I also see it as a blow to mental health if it is seen as pejorative and inappropriate to suggest that a person has mental health issues. The review was keen on the promotion of graded exercise.
According to the news agency Reuter’s, dozens of researchers in the field of CFS worldwide suffer a campaign to discredit their work and this discourages them from working in the field and improving the care that they have to offer.18Online Activists Are Silencing Us, Scientists Say The article says, “Reuters spoke to three specialists in CFS/ME in Britain, Denmark and the Netherlands who have reported receiving online abuse but continue to work in the field. The specialist in the Netherlands, a psychologist who works at a chronic fatigue treatment centre, said that a few years ago, research teams there had five treatment studies looking at cognitive behavioural therapies for CFS/ME patients. Now, they have no treatment studies at all. Junior researchers are wary of entering the field because of the abuse they have seen others suffer, said the specialist in Britain, a doctor who spoke on condition of anonymity.”
This is an appalling state of affairs but for many scientists, this is a new normal. As we have seen before, science is about evidence, not wishful thinking or political correctness. Attempts to bend science to the will of others is reminiscent of the age when the Inquisition would insist on “corrections”. From climate change to vaccines, activism and science are fighting it out online with lies and abuse rather than evidence and reason. Social media platforms are enhancing the battle. Doctors and scientists are people who want to do well for others. They do not want their daily life to be a battle against hurtful abuse. When an organisation as illustrious and independent as Cochrane succumbs to intimidation, it is a very sad day. If they opt out in the face of this abuse, the patients will suffer. The online trolls are hurting those whom they claim to champion.
Dr Michael O’Donnell’s words from his famous Sceptic’s Medical Dictionary ring true. Sufferers are too fatigued to do graded exercise but not too fatigued to be vicious online trolls.
- Centers for Disease Control and Prevention (USA) Chronic Fatigue Syndrome.
An American resource of good and reliable evidence-based advice
- Craig T, Kakumanu S. Chronic fatigue syndrome: evaluation and treatment. Am Fam Physician. 2002 Mar 15;65(6):1083-90. [full text]
Again American and designed for doctors but may be interesting
- Department of Health. Occupational aspects of the management of chronic fatigue syndrome: evidence based guidance.
Good advice from the NHS.
- Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management.
As always, sound, evidence-based advice from NICE
- Crowley N, Nelson M, Stovin S. Epidemiological aspects of an outbreak of encephalomyelitis at the Royal Free Hospital, London, in the summer of 1955. J Hyg (Lond). 1957 Mar; 55(1): 102–122.
- Mihrshahi R, Beirman R. Aetiology and pathogenesis of chronic fatigue syndrome: a review. N Z Med J. 2005 Dec 16;118(1227):U1780
- Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev. 2009 Feb;8(4):287-91.
- Cliff JM, King EC, Lee JS, Sepúlveda N, Wolf AS, Kingdon C et al Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) J Transl Med. 2015; 13: 299. [full text]
- Hardcastle SL, Brenu EW, Johnston S, Nguyen T, Huth T, Ramos S. et al. Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. J Transl Med. 2015 Sep 14;13:299. [full text]
- Capelli E, Zola R, Lorusso L, Venturini L, Sardi F, Ricevuti G. Chronic fatigue syndrome/myalgic encephalomyelitis: an update. Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):981-9.
- Institute of Medicine (USA) diagnostic criteria for CFS 2015
- NICE Guidance CG53 August 2007.
- Jones JF, Maloney EM, Boneva RS, Jones AB, Reeves WC. Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States. BMC Complement Altern Med. 2007 Apr 25;7:12. [full text]
- Chambers D, Bagnall AM, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med. 2007 Jan;100(1):7.[full text]
- Shephard RJ. Chronic fatigue syndrome. A brief review of functional disturbances and potential therapy. J Sports Med Phys Fitness. 2005 Sep;45(3):381-92
- NICE. Guideline 5 Myalgic encephalomyelitis (or 6 encephalopathy)/chronic fatigue syndrome: 7 diagnosis and management. November 2020.
- Wearden AJ, Morriss RK, Mullis R, et al. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry. 1998 Jun;172:485-90.
- Larun L, Brurberg K, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2017
- Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001027.
- Bentall RP, Powell P, Nye FJ, Edwards RH. Predictors of response to treatment for chronic fatigue syndrome. Br J Psychiatry. 2002 Sep;181:248-52. [full text]
- Exclusive: Science journal to withdraw chronic fatigue review amid patient activist complaints. Reuters 17th October 2018
- Online Activists Are Silencing Us, Scientists Say. Reuters 13th March 2019
This website is now completed, although I shall continue to do updates. The following list shows the sections or chapters. Just click on the topic in blue to go to that part of the site.