05 May 2015
Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome:
Not Just Tired All The Time!
Dr Alastair Miller
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex and controversial condition that is thought to affect between 0.2 and 0.4% of the UK population (a quarter to half a million).
In the US, the estimated prevalence is between 1 and 2.5 million and its human, economic and social impact is enormous. Despite decades of research that has accelerated rapidly in recent years, the fundamental mechanisms that produce its well defined pattern of symptoms remain elusive.
Symptoms are adverse experiences or feelings described by a patient. They are therefore subjective and the process of eliciting a pattern of symptoms from a patient is known as “taking a history”. Examples of symptoms would be headache, nausea or breathlessness.
Signs (sometimes known as physical signs) are objective abnormalities identified when a doctor (or other clinician) performs a physical examination of a patient. Examples of physical signs would be a rapid pulse rate, a rash or a mass in the abdomen.
Symptoms and signs taken together are often referred to as the clinical features of a patient’s condition. “Clinical” comes from the Greek for bed and therefore clinical features refer to those that can be identified “at the bedside” without recourse to the laboratory or x-ray department. A characteristic pattern of symptoms and signs is referred to as a syndrome (sometimes a clinical syndrome).
Diagnosis is defining exactly what is wrong with the patient. Recognising a syndrome allows the attending clinician to suspect a diagnosis and they will then usually attempt to confirm the diagnosis by performing a number of investigations. “Investigations” is a blanket term used to describe the evaluation of patients that takes place in the laboratory by tests on blood and other body fluids or tissue and in the imaging departments by x-rays or scans.
Diagnosis can be at varying levels of sophistication. For example, a patient presenting to a clinician with a combination of headache, fever, vomiting and neck stiffness has a syndrome that suggests meningitis (inflammation of the covering of the brain- the meninges- usually caused by infection). This would be called a clinical diagnosis of meningitis. The condition should then be confirmed by performing a lumbar puncture and if that shows inflammation in the cerebro-spinal fluid obtained then the diagnosis is confirmed.
Later, a specific organism in the cerebro-spinal fluid may be identified, refining the diagnosis to one of, for example, meningococcal meningitis. Once the mechanism producing the symptoms has been demonstrated then a syndrome tends to be called a disease.
Much effort of clinicians is directed towards establishing a diagnosis because once we know what is going on, then the management (treatment) of the condition may become more apparent.
History of CFS/ME
There are historical descriptions of those who almost certainly had CFS/ME going back well into the 19th century. It is likely that Florence Nightingale was an early sufferer. After her return from the Crimean War she spent several years housebound and was unable to see more than one visitor at a time. Many patients were described after the First World War and the condition was often referred to as neurasthenia or effort syndrome.
The term Myalgic Encephalomyelitis was first used in 1955 following an outbreak of an apparent viral illness at the Royal Free Hospital in London. The main clinical features were fever, headache, swollen glands, cognitive disturbance, muscle pain (myalgia) and numbness (tingling – parasthesiae) in the extremities.
There was a total of 292 cases including 72 clinical staff and the hospital was closed between July and October. No specific virus was ever implicated and the condition was known as Myalgic because of the profound muscle pain and Encephalomyelitis because the combination of the cognitive difficulty and the parasthesiae suggested some inflammatory condition of the brain and spinal cord.
Various other outbreaks of similar conditions were described in the 1960s and perhaps the early controversy around the condition was triggered in the 1970s when two British psychiatrists suggested that the conditions had been caused by mass hysteria.
In the US there was a similar outbreak of a viral illness amongst an affluent skiing community in Lake Tahoe in the mid 1980s and this again was followed by a protracted illness that was colloquially known as “yuppie flu”. There was a feeling at the time that it may have been caused by a chronic viral infection similar to infectious mononucleosis (glandular fever) caused by Epstein Barr virus but it soon became clear that this was not the case.
In 1988 the term Chronic Fatigue Syndrome (CFS) was coined for the first time.
The definition of CFS was refined by the Centers for Disease Control (in Atlanta, Georgia, US) in 1994. The diagnostic criteria were laid down in a paper where the first author was Fukuda and these have become widely known as the Fukuda criteria for the diagnosis of CFS.
In 1996 a report was commissioned by three of the UK Medical Royal Colleges (London Royal College of Physicians, the Royal College of Psychiatrists and the Royal College of General Practitioners). This was followed by a further report of the UK Chief Medical Officer (Liam Donaldson) in 2002.
In 2007 the National Institute for Health and Care Excellence (NICE) produced a guideline (CG53) that remains the current evidence base for the management of CFS/ME.
2011 saw the publication of the Medical Research Council (MRC) sponsored PACE trial that gave further support to the NICE guidelines.
In 2013 a major impetus to research in CFS/ME was achieved with the formation of the UK CFS/ME Research Collaborative (CMRC) that brought together the MRC, research institutes, CFS/ME charities and the British Association for CFS/ME (BACME) – the professional and specialist society for healthcare professionals and prominent individual researchers to provide cross pollination and collaborative research.
Who cares for CFS/ME?
There is no such thing as an accredited specialist in purely CFS/ME. Therefore the clinical care for patients will come from a variety of different specialists. Because the initial presenting symptoms may vary quite widely, patients may come to a variety of clinicians including GPs, hospital physicians in a variety of specialties (including neurology, endocrinology, infectious disease, rheumatology, immunology) psychiatrists and clinical psychologists.
After the 2002 CMO report a network of NHS specialist referral centres was established and most of them still exist but many are under threat in the current era of NHS austerity. These brought together multi-disciplinary teams (medical, nursing, therapists and psychologists) to provide evidence-based care for patients and in general produced good outcomes recorded and reported in the National Outcomes Database (Crawley et al. QJM. 2013; 106(6): 555–565).
Regrettably the condition has a relatively low profile in many undergraduate and postgraduate medical curricula.
Definition and diagnosis
There are several different criteria for the diagnosis and definition of CFS/ME and like most components of this condition they arouse strong feelings and controversy. The most commonly used criteria probably remain the Fukuda criteria (Fukuda et al. Ann Int Med 1994; 121:953) published by CDC in 1994. These require fatigue that isclinically evaluated, unexplained and
- lasting more than six months, not lifelong
- not result of exertion
- not relieved by rest
- causing significant functional disability.
Additionally, patients must have at least four of the following accompanying features
- sore throat
- tender swollen glands
- cognitive dysfunction
- new headaches
- unrefreshing sleep
- post exertion malaise.
Numerous other definitions exist including the Oxford criteria, the International Consensus Criteria and the Canadian criteria. In practice these are all too cumbersome for day to day clinical use and their main utility is as research tools for recruitment into clinical trials.
In CFS/ME there are no characteristic abnormalities on physical examination (ie. no “signs”) and no characteristic laboratory abnormalities so the diagnosis is made entirely on the history (ie. the pattern and evolution of the symptoms).
Many people say that it is a “diagnosis of exclusion” ie. one excludes all other possible causes of fatigue by laboratory tests and then concludes it must be CFS/ME.
In practice most clinicians experienced in this area feel that the pattern of symptomatology is so characteristic that a positive clinical diagnosis can be made.
Notwithstanding the criteria above (which as noted are probably more relevant to research trials than clinical practice), most clinicians would feel that the absolutely critical features are cognitive problems (often referred to by patients as “brain fog”), worsening of all symptoms by any form of mental or physical exertion (often referred to as “pay-back”), disturbed sleep and pain.
If any of these features is missing then the diagnosis must be seriously questioned.
This point is emphasized in the recent US Institute of Medicine report (2015. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, DC: The National Academies Press)
It is clearly important to consider other causes of fatigue and the NICE guideline suggests that a certain number of routine investigations are undertaken:
- Full blood count
- U&Es, LFTs, Thyroid function, Calcium, Creatinine, CPK, glucose
- CRP and ESR or plasma viscosity
- Test for gluten sensitivity (coeliac).
In practice, though, the symptoms of CFS/ME are very different from those of someone with an undiagnosed cancer, chronic infection or chronic inflammatory condition (such as rheumatoid arthritis).
However, the potential differential diagnosis is quite wide and includes all of the conditions listed below:
Infection: TB, Endocarditis, HIV, Hepatitis, Brucella (NOT Lyme)
Cancer: both blood cancers such as Leukaemia, Lymphoma and solid organ cancer
Neurological conditions: Myaesthenia, MS, Parkinsons Disease
Endocrine: diabetes, thyroid, adrenal, pituitary, calcium disorders
Mental health problems: anxiety, depression, psychosis
Others: SLE, narcolepsy, sleep apnoea, depression, alcohol, drugs, obesity
Difficult to assess contribution of drugs (eg. beta blockers)
CFS/ME remains a “medically unexplained syndrome” in that we have no unifying theory of the basic mechanism that underlies the production of the symptoms. We cannot explain the symptoms on a physiological, immunological, structural or biochemical basis. Despite all the current research we have no specific target for drug development. We therefore have no drug that can influence the natural history or prognosis of CFS/ME.
We can use drugs to ameliorate some of the symptoms such as pain, depression, nausea etc although characteristically, patients with CFS/ME often do not derive much benefit from drug therapy and are often intolerant of drugs. BACME is just about to publish a guide aimed at GPs and other clinicians about an approach to symptom management in CFS/ME.
The only current therapeutic approach for which there is some evidence is using either cognitive behaviour therapy (CBT) or graded exercise therapy (GET). These are controversial approaches because some patients feel it incongruous that they are told that CFS/ME is not a “psychological condition” and yet we are going to use a psychological therapy for it.
However, CBT is extensively and beneficially employed in many other chronic conditions such as cancer and rheumatoid arthritis, so there is nothing illogical in using it for CFS/ME. It does not work for everyone but it is unlikely to cause any harm (White at al. Lancet 2011; vol 377; issue 9768) and is worth trying.
CFS/ME despite a huge research effort remains an ill understood and “medically unexplained syndrome”. It is capable of a positive diagnosis although there is no specific test or biomarker. It should be specifically diagnosed either in primary or secondary care and consideration should be given to referring patients for specific therapies.
About the author
Alastair Miller was a Consultant Physician in the Tropical & Infectious Disease Unit at the Royal Liverpool University Hospital and an Honorary Fellow at the Liverpool School of Tropical Medicine 2005 until May 2014. He remains an Honorary Senior Lecturer at The Institute of Infection and Global Health at Liverpool University. Prior to Liverpool he was a Consultant in the West Midlands and Honorary Senior Lecturer in Infectious Disease at Birmingham University. His main clinical interests are blood borne viruses, bone and joint infection and CFS/ME.
Alastair trained in medicine at St John’s College, Cambridge and Westminster Medical School and in infectious disease in the Royal Navy, Birmingham and London (St George’s Hospital and the London School of Hygiene & Tropical Medicine). He worked with the Royal Marines in Kurdistan after the first Gulf War and was a consultant and Professor of Medicine in the Royal Navy. He left the Navy as a Surgeon Commander in 1995.
He has been involved clinically with ME/CFS since his time as a registrar in the mid 1980s. In the Navy he was the lead clinician and in Worcestershire he established a multidisciplinary team for CFS management. Since arriving in Merseyside he became the clinical lead for CFS and ran a diagnostic clinic and a therapy service in collaboration with therapy and psychology colleagues.
He has been involved in CFS/ME research and teaching for many years. He reviewed all the adverse events for the PACE trial and is on the steering committee for the GETSET trial. He is Chair of the British Association for CFS/ME (BACME) and Principal Medical Advisor for Action for M.E. He has taught on courses and provided consultancy advice for the Department of Work & Pensions on CFS/ME.
Alastair also has a particular interest in Medical Education. He chaired the Specialist Advisory Committee on Infectious Disease and Tropical Medicine for six years. He is Deputy Medical Director of the Joint Royal Colleges of Physicians Training Board (JRCPTB) and an examiner for the MRCP(UK).
Alastair retired from Liverpool in 2014 to spend more time in the mountains but continues to work one day a week in London at JRCPTB and one day a week in acute medicine for Northumbria Acute NHS Trust
His outside interests are sailing and mountaineering. He has been a member of the Alpine Club since 1986. He has been to 8000 metres on the North Face of Everest and has climber extensively in the UK and European Alps. He has been to the summit of Mt Kilmanjairo, Mt Kenya, Mt McKinley and Mt Kinabalu. He is also a keen ski mountaineer and fell runner.
© Dr Alastair Miller, 2015