Patient professional reference
Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use. You may find the Chronic Fatigue Syndrome (Myalgic Encephalomyelitis) article more useful, or one of our other health articles.
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a complex, chronic medical condition characterised by symptom clusters that include pathological fatigue and malaise that is worse after exertion, cognitive dysfunction, immune dysfunction, unrefreshing sleep, pain, autonomic dysfunction and also neuroendocrine and immune symptoms. The condition is common and is often severely disabling.
ME (or CFS) is a complex disorder of unknown aetiology with persistence of symptoms of at least six months. However the National Institute for Health and Care Excellence (NICE) recommends that the diagnosis be made when other possible diagnoses have been excluded and symptoms have persisted for four months in an adult, or three months in a child (this should be made by a paediatrician).
There remains a great deal of controversy about every aspect of the condition, including aetiology, definition, clinical features and management. While often having been considered as a psychological problem, many authorities believe that it represents a whole variety of underlying illnesses, some psychological or due to anxiety-related exercise intolerance, but many others caused by neurological impairment, energy-production impairment or autoimmune dysfunction.
Diagnosing the disease remains a challenge. Patients often struggle with their illness for years before an identification is made. Once diagnosed, patients often complain of receiving hostility from their healthcare provider as well as being subjected to treatment strategies that exacerbate their symptoms.
- ME is not uncommon but the true prevalence is unknown and depends on the criteria used for diagnosis.
- NICE suggests a prevalence of 4 per 1,000 in the UK.
- Women appear to be affected more than men, with the ratio reported as being female:male 2:1.
- ME can affect children and research has shown a higher incidence in socially deprived families.
- Numerous factors, including previous psychiatric disorder, stressful events, high academic achievement, infections and many others, have been suggested as having a role to play in the aetiology of the disease. However, there is little firm evidence available.
- Epidemics of ME have been reported in several areas but no causative organism has been found. There is some debate as to whether the chronic fatigue associated with these outbreaks may be a different form of the disorder.
Sometimes reaching a diagnosis can be problematic for a number of reasons:
- The onset may be relatively sudden or gradual, following a physical illness or stressful event, or apparently out of the blue.
- The range of presenting symptoms is wide; fatigue and pain may not always be the prominent disabling features at initial presentation.
- Patients may have been investigated extensively, without positive findings, for varied physical symptoms and may feel frustrated by the lack of help received from the medical profession by the time the diagnosis is made.
- Cognitive difficulties represent a common and debilitating feature of ME. These difficulties manifest as self-reported problems with attention, memory and concentration, presenting objectively as slowed information processing speed particularly on complex tasks requiring sustained attention.
- Symptoms tend to vary in intensity and type over a period of weeks or months (and evolve into what is more clearly ME with time), leading to uncertainty for both the patient and clinician about the course and nature of the underlying problem.
- None of the current diagnostic methods has been adequately tested to identify patients with ME when diagnostic uncertainty exists.
- ME cannot be diagnosed by any test currently available.
- The lack of consensus on how recovery should be defined or interpreted has also generated controversy and confusion.
- Headache of new type, pattern, or severity.
- Multi-joint pain without swelling or erythema.
- Muscle pain.
- Post-exertional malaise for longer than 24 hours.
- Significant impairment in short-term memory or concentration.
- Sore throat.
- Tender lymph nodes.
- Unrefreshing sleep.
Myalgic encephalomyelitis (ME) has been described in the medical literature since 1938. It is characterised by distinctive muscular symptoms, neurological symptoms and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, was chronic fatigue, which should be accompanied by at least four or more out of eight 'additional' symptoms. The criteria of CFS define a heterogeneous patient population.
An International Consensus in 2011 considered that the label 'chronic fatigue syndrome' had persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly pointed to widespread inflammation and multisystemic neuropathology, it was considered to be more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because this indicates an underlying pathophysiology. This term will be used throughout this article. The criteria used for ME in adults included:
- Post-exertional neuroimmune exhaustion.
- Neurocognitive impairments.
- Neurosensory, perceptual and motor disturbances.
- Immune, gastrointestinal and genitourinary impairments.
- Energy production/transportation impairments.
The US Institute of Medicine has proposed that a new clinical entity - systemic exercise intolerance disease (SEID) - should replace the clinical entities ME and CFS. Until consensus is finally reached on terminology, we have chosen to use ME throughout our articles where appropriate.
In addition to the symptoms used to define the disorder, several other symptoms have been described:
- General: night sweats, weight loss, alcohol intolerance.
- Gastrointestinal: abdominal pain, bloating, diarrhoea.
- Respiratory/cardiovascular: chronic cough, chest pain, neurally mediated hypotension, shortness of breath.
- Psychological: anxiety, panic attacks, depression, irritability.
- Mild: the patient is mobile and can care for themself and do light housework with difficulty.
- Moderate: the patient has reduced mobility and is restricted in all activities of daily living. They have usually stopped work or education. There is poor sleep quality and duration.
- Severe: the patient is unable to do anything for themself. They have severe cognitive difficulties and depend on a wheelchair. They spend most of their time in bed and are sensitive to light and noise.
The differential diagnoses are many and varied. They will vary from patient to patient, depending on the initial presentation. See also the separate Fatigue and TATT article.
- Hypothyroidism, diabetes and anaemia should be considered as causes of fatigue.
- Systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease should be considered as causes of arthralgia.
- Underlying neoplasia should be considered as a cause of lymphadenopathy.
- Metabolic muscle disorders and myopathies should be considered as a cause of muscle pain and weakness.
- Psychiatric illness should be considered as a cause of depression and anxiety.
- Cardiological or respiratory causes should be considered for shortness of breath and chest pain, and many other illnesses, depending on the specific symptoms
- Localising/focal neurological signs.
- Signs of inflammatory arthritis or connective tissue disease.
- Signs of cardiorespiratory disease.
- Significant weight loss.
- Sleep apnoea.
- Significant lymphadenopathy.
There is no currently available biomedical test which can be used to diagnose ME and it remains a diagnosis of exclusion. A full medical and psychosocial history and a thorough physical and mental state examination are essential.
In a patient in whom the diagnosis is suspected, the laboratory investigations performed are those required to rule out other causes of illnesses which may mimic ME:
- Renal function and electrolytes, LFTs, TFTs.
- FBC, serum ferritin, ESR or plasma viscosity.
- Blood glucose.
- Test for gluten sensitivity.
- Antinuclear antibodies, rheumatoid factor.
- Creatine kinase.
- Urinalysis for protein, blood and glucose.
NICE recommends that the 'tilt table test' (laying the patient horizontally on a table, then tilting the table upright to 70° for 45 mins while measuring pulse and blood pressure) should NOT be routinely performed. Patients with ME have been found to have disordered autonomic regulation and develop hypotension during this procedure.
NICE also advises that auditory brainstem response and electrodermal conductivity tests should NOT be routinely performed.
Reconsider the diagnosis if the patient does not have:
- Post-exercise fatigue
- Cognitive problems
- Sleep disturbance
- Chronic pain
There is considerable controversy with regard to appropriate treatments for people with ME. Treatments that are effective for some people may be ineffective or even detrimental for others. This is consistent with our current lack of understanding of ME and the likelihood that the term is an umbrella for a range of different conditions.
The main points from the NICE guidance are:
- Shared decision making with the patient and their carer/s.
- Identifying and managing symptoms early on, in ways that are suitable for that particular patient.
- Making an accurate diagnosis and considering differential diagnoses and co-existing morbidity.
Treatment options include cognitive behavioral therapy (CBT) and graded exercise therapy, both of which have been shown to moderately improve fatigue levels, work and social adjustment, anxiety, and post-exertional malaise. People with ME should be evaluated for concurrent depression, for pain and for sleep disturbances.
A major randomised trial comparing adaptive pacing therapy (APT), CBT, graded exercise therapy (GET) and specialised medical care for ME (the 'PACE' trial) found that CBT and GET can safely be added to specialised medical care to moderately improve outcomes for ME but that APT was not an effective addition.
Long-term follow-up of the PACE trial found that the initially reported beneficial effects of CBT and GET, seen at one year, were maintained at long-term follow-up at a median of 2·5 years after randomisation. Outcomes with specialised medical care alone or APT improved from the one-year outcome and were similar to CBT and GET at long-term follow-up; however, these data should be interpreted in the context of additional therapies having being given according to physician choice and patient preference after the one-year trial final assessment. It was recommended that future research should identify predictors of response to CBT and GET and also develop better treatments for those who respond to neither.
Other studies have reported that CBT and GET are effective treatments for ME. However, one study found that there may be similar or poorer outcomes when used in routine clinical practice.
People with ME may generally benefit and feel less fatigued following exercise therapy. There is currently no evidence suggesting that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been seen but no conclusive evidence for the outcomes of pain, quality of life, anxiety or depression. The effectiveness of exercise therapy seems greater than that of APT but similar to that of CBT.
However, some studies have shown that, although CBT may bring about changes in self-reported fatigue for some patients in the short term, there is a lack of evidence for long-term benefit or for improving physical function, indicating that CBT may cause distress if used inappropriately.
The management of ME is controversial and it is considered by some that CBT and GET may not only be ineffective and not evidence-based but also potentially harmful for many people with ME.
Pharmacological and complementary treatments
No pharmacological or complementary therapy has yet been proven to be effective[10, 14]. However, one large review found that trials of rintatolimod (an immune modulator), counselling therapies and graded exercise therapy suggested benefit for some patients meeting case definitions for ME, whereas evidence for other treatments and harms was insufficient.
Although there is no evidence to support the use of any therapeutic regime to modify the course of the disorder, individual symptoms may be helped by appropriate therapy, including:
- The use of non-sedating antidepressive agents such as fluoxetine may be beneficial for the treatment of depression. An early assessment by the psychiatric services may also be required in severe cases.
- Non-steroidal anti-inflammatory agents such as ibuprofen may be helpful in the treatment of myalgias and arthralgias.
- Consider a low-dose tricyclic antidepressant for poor sleep or pain but NOT if the patient is already taking a selective serotonin reuptake inhibitor.
- Melatonin may be used in children with sleep difficulties, under specialised supervision.
This should be offered if:
- The patient is a child within six weeks of presentation.
- The patient has severe ME symptoms.
It may also be considered after six months in mild ME, or 3-4 months in moderate ME, depending on symptoms and comorbidity.
- The prognosis and clinical course of the disorder vary considerably. Some patients recover to the extent that they are able to continue virtually normal activities, with periodic ME symptoms.
- Lower recovery rates and higher relapse rates are associated with those who have had ME for many years.
- Children can be very severely afflicted but those whose symptoms are of mild-to-moderate severity are generally more likely than adults to go into remission.
Further reading and references
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis - A Primer for Clinical Practitioners; International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Geraghty KJ, Esmail A; Chronic fatigue syndrome: is the biopsychosocial model responsible for patient dissatisfaction and harm? Br J Gen Pract. 2016 Aug66(649):437-8. doi: 10.3399/bjgp16X686473.
Bested AC, Marshall LM; Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians. Rev Environ Health. 201530(4):223-49. doi: 10.1515/reveh-2015-0026.
Moss-Morris R, Deary V, Castell B; Chronic fatigue syndrome. Handb Clin Neurol. 2013110:303-14. doi: 10.1016/B978-0-444-52901-5.00025-3.
Chronic fatigue syndrome/Myalgic encephalomyelitis (or encephalopathy) diagnosis and management; NICE Clinical Guideline (August 2007)
Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations Institute of Medicine
Nacul LC, Lacerda EM, Pheby D, et al; Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care. BMC Med. 2011 Jul 289:91. doi: 10.1186/1741-7015-9-91.
Crawley E; The epidemiology of chronic fatigue syndrome/myalgic encephalitis in children. Arch Dis Child. 2014 Feb99(2):171-4. doi: 10.1136/archdischild-2012-302156. Epub 2013 Oct 21.
Cvejic E, Birch RC, Vollmer-Conna U; Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence. Curr Rheumatol Rep. 2016 May18(5):24. doi: 10.1007/s11926-016-0577-9.
Haney E, Smith ME, McDonagh M, et al; Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16162(12):834-40. doi: 10.7326/M15-0443.
Adamowicz JL, Caikauskaite I, Friedberg F; Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res. 2014 Nov23(9):2407-16. doi: 10.1007/s11136-014-0705-9. Epub 2014 May 3.
Yancey JR, Thomas SM; Chronic fatigue syndrome: diagnosis and treatment. Am Fam Physician. 2012 Oct 1586(8):741-6.
Carruthers BM, van de Sande MI, De Meirleir KL, et al; Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011 Oct270(4):327-38. doi: 10.1111/j.1365-2796.2011.02428.x. Epub 2011 Aug 22.
Twisk FN; Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward. Diagnostics (Basel). 2016 Feb 56(1). pii: E10. doi: 10.3390/diagnostics6010010.
Naschitz JE, Rosner I, Rozenbaum M, et al; The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. QJM. 2003 Feb96(2):133-42.
White PD, Goldsmith KA, Johnson AL, et al; Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5377(9768):823-36. Epub 2011 Feb 18.
Sharpe M, Goldsmith KA, Johnson AL, et al; Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry. 2015 Dec2(12):1067-74. doi: 10.1016/S2215-0366(15)00317-X. Epub 2015 Oct 28.
Fernie BA, Murphy G, Wells A, et al; Treatment Outcome and Metacognitive Change in CBT and GET for Chronic Fatigue Syndrome. Behav Cogn Psychother. 2016 Jul44(4):397-409. doi: 10.1017/S135246581500017X. Epub 2015 Apr 21.
Larun L, Brurberg KG, Odgaard-Jensen J, et al; Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2016 Jun 24(6):CD003200. doi: 10.1002/14651858.CD003200.pub5.
Geraghty KJ, Blease C; Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent. J Health Psychol. 2016 Sep 15. pii: 1359105316667798.
Twisk FN, Maes M; A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 200930(3):284-99.
Smith ME, Haney E, McDonagh M, et al; Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16162(12):841-50. doi: 10.7326/M15-0114.
Hi all, I’m 32 and a mum of three little boys. I have recently been diagnosed with CFS and am struggling so much with life. Most days I suffer to the point I feel I cannot cope and feel like it’s...lisa10692
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