Myalgic encephalomyelitis (Chronic fatigue syndrome)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, multisystemic, and disabling condition.

A history of post-exertional malaise (PEM), also known as post-exertional neuroimmune exhaustion (PENE), for a minimum of 6 months is considered a defining key symptom. PEM occurs when exertion and other stressors lead to symptom exacerbations with immediate or delayed onset. Although many of the symptoms commonly reported in ME/CFS may occur in several other diseases, the presence of PEM should always prompt consideration of ME/CFS.

Although diagnostic criteria stipulate that diagnosis in adults should not be made until after 6 months of symptoms (3 months for children) and negative medical evaluation, the 2021 UK National Institute for Health and Care Excellence (NICE) guidance discusses the negative impact of a 6-month delay in starting management. NICE therefore recommends that observation in adults be reduced to 3 months before initiating therapy.

There are no objective diagnostic tests, verified biomarkers, curative medications, or treatments for ME/CFS. The primary goals of treatment are to manage symptoms and improve functional capacity. Initial treatment should be individualised based on the patient’s most severe complaints.

The chronic but fluctuating debilitating symptoms require substantial lifestyle changes to carefully plan each day's activities, conserve energy resources for the most important tasks, schedule rest periods to avoid individuals overtaxing themselves, and to improve the quality of sleep.

Primary care clinicians play a key role in management of patients with ME/CFS, typically retaining responsibility for long-term care and monitoring, in partnership with the ME/CFS specialist team in secondary care.

There is substantial overlap between ME/CFS and long-term post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (long COVID), which will be a continuing issue for evaluation.

ME/CFS is characterised by a sudden or gradual onset of persistent disabling fatigue, post-exertional malaise (PEM), unrefreshing sleep, cognitive and autonomic dysfunction, and pain, with symptoms lasting at least 6 months.[1]Komaroff AL. Myalgic encephalomyelitis/chronic fatigue syndrome: a real illness. Ann Intern Med. 2015 Jun 16;162(12):871-2. https://www.acpjournals.org/doi/10.7326/M15-0647 http://www.ncbi.nlm.nih.gov/pubmed/26075760?tool=bestpractice.com  These symptoms are otherwise unexplainable and persist for at least 6 months, are not alleviated by rest, and significantly impair quality of life. The World Health Organization (WHO) International Classification of Diseases (ICD) classifies ME/CFS as a disease of the nervous system.[2]World Health Organization. International classification of diseases 11th revision for mortality and morbidity statistics (ICD-11 MMS). Jan 2023 [internet publication]. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/569175314  

There exist several diagnostic criteria for ME/CFS for which there is variation in the use of the terms ME, CFS, and ME/CFS (often, but not always, used interchangeably by clinicians). The term 'myalgic encephalomyelitis' was first introduced to differentiate chronic fatigue from other illnesses and to characterise the prevalence of muscle pain and inflammation of the brain; however, this is problematic, given the limited evidence for brain inflammation. Subsequently, the US Centers for Disease Control and Prevention (CDC) published a criteria in 1988 proposing the name 'chronic fatigue syndrome'. Many patients consider the name 'chronic fatigue syndrome' overly simplistic given the heterogeneity of symptoms, and some may regard the term as derogatory. ME/CFS is often incorrectly confused with or considered to be equivalent to chronic fatigue.

Diagnosis is complicated by the presence of 9 sets of subjective clinical criteria. Definitions of ME/CFS have evolved from a focus on fatigue and impairment as described in the CDC criteria, to PEM/exertional exhaustion in ME/CFS as defined by the Canadian Consensus Criteria (CCC). Systemic exertion intolerance disease (SEID) was introduced as an alternative term in 2015 by the Institute of Medicine (IOM; now the National Academy of Medicine).[3]Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9. http://www.ncbi.nlm.nih.gov/pubmed/7978722?tool=bestpractice.com [4]Carruthers BM, Jain AK, De Meirleir KL, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J Chron Fatigue S. 2003 Dec;11(1):7-115. https://www.mefmaction.com/images/stories/Medical/ME-CFS-Consensus-Document.pdf [5]Jason LA, Evans M, Porter N, et al. The development of a revised Canadian myalgic encephalomyelitis chronic fatigue syndrome case definition. Am J Biochem Biotechnol. 2010;6(2):120-35. http://thescipub.com/pdf/10.3844/ajbbsp.2010.120.135 ​​ SEID was defined based on an extensive review of the literature, and was proposed to emphasise that dysfunction involves the entire body, and that it is aggravated by physical or cognitive exertion and other stressors.[6]Institute of Medicine of the National Academies. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Feb 2015 [internet publication]. https://www.nap.edu/catalog/19012/beyond-myalgic-encephalomyelitischronic-fatigue-syndrome-redefining-an-illness [7]Jason LA, Brown A, Evans M, et al. Contrasting chronic fatigue syndrome versus myalgic encephalomyelitis/chronic fatigue syndrome. Fatigue. 2013 Jun 1;1(3):168-83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728084 http://www.ncbi.nlm.nih.gov/pubmed/23914329?tool=bestpractice.com ​ Use of the term SEID is not currently widespread, and within this topic the nomenclature ME/CFS is used. 

Newer diagnostic criteria emphasise the importance of PEM as a key, defining feature of ME/CFS.[6]Institute of Medicine of the National Academies. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Feb 2015 [internet publication]. https://www.nap.edu/catalog/19012/beyond-myalgic-encephalomyelitischronic-fatigue-syndrome-redefining-an-illness [7]Jason LA, Brown A, Evans M, et al. Contrasting chronic fatigue syndrome versus myalgic encephalomyelitis/chronic fatigue syndrome. Fatigue. 2013 Jun 1;1(3):168-83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728084 http://www.ncbi.nlm.nih.gov/pubmed/23914329?tool=bestpractice.com PEM has been described as a group of symptoms following mental or physical exertion, lasting 24 hours or more. The exertion, or other stressors, lead to symptom exacerbations with onset immediately or delayed by several hours or overnight.[8]National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. Oct 2021 [internet publication]. https://www.nice.org.uk/guidance/ng206  Symptoms of PEM include fatigue, headaches, muscle aches, cognitive deficits, and insomnia. It can occur after even simple tasks (e.g., walking, or holding a conversation) and requires people to make significant lifestyle changes to conserve their physical resources and mental concentration to stay competent in normal occupational, educational, and social settings.[9]Jason LA, Evans M, So S, et al. Problems in defining post-exertional malaise. J Prev Interv Community. 2015;43(1):20-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295644 http://www.ncbi.nlm.nih.gov/pubmed/25584525?tool=bestpractice.com  Patients are often limited to a few hours per day of productive endeavours, with the remainder of the time spent resting with slow and partial recovery of their debilitating symptoms.

Although diagnostic criteria stipulate that diagnosis in adults should not be made until after 6 months of symptoms (3 months for children) and negative medical evaluation, the 2021 UK National Institute for Health and Care Excellence (NICE) guidance discusses the negative impact of a 6-month delay in starting management. NICE therefore recommends that observation in adults be reduced to 3 months before initiating therapy.[8]National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. Oct 2021 [internet publication]. https://www.nice.org.uk/guidance/ng206 ​

In the evaluation of a patient with prolonged, unremitting, and disabling fatigue, it is essential that clinicians carefully apply appropriate modern terminology, and classify ME/CFS according to more recent criteria. See Diagnostic approach.