Chronic fatigue syndrome/Myalgic encephalomyelitis

Chronic fatigue syndrome/encephalomyelitis (CFS/ME) can be distinguished from medical and psychiatric conditions in the differential diagnosis of fatigue by the presence of debilitating fatigue for more than 6 months; combinations of cognitive dysfunction, total body pain, and unrefreshing sleep that does not restore normal function; and postexertional malaise, where exertion or other stressors leads to exacerbation of these symptoms with onset immediately or delayed by several hours or overnight

The World Health Organization classifies CFS/ME as a neurological illness.

There are no objective diagnostic tests, verified biomarkers, curative medications, or treatments for CFS/ME. 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 disabilities 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.

Up to 30.5% of the population have chronic fatigue. [1] van't Leven M, Zielhuis GA, van der Meer JW, et al. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010 Jun;20(3):251-7. https://academic.oup.com/eurpub/article/20/3/251/429061 http://www.ncbi.nlm.nih.gov/pubmed/19689970?tool=bestpractice.com Therefore, it is necessary to carefully consider diagnostic criteria and exclusionary conditions in the evaluation of a patient with prolonged unremitting fatigue.

There are several diagnostic criteria for CFS/ME in common clinical usage. There is also variation and controversy in the use of the terms ME, CFS, and ME/CFS (often, but not always, used interchangeably by clinicians). Many patients consider the name 'chronic fatigue syndrome' overly simplistic, and pejorative. The term 'myalgic encephalomyelitis' is also problematic, given the limited evidence for brain inflammation.

CFS/ME is characterised by a sudden or gradual onset of persistent disabling fatigue, post-exertional malaise (PEM)/exertional exhaustion, unrefreshing sleep, cognitive and autonomic dysfunction, myalgia, arthralgia, headaches, and sore throat and tender lymph nodes (without palpable lymphadenopathy), with symptoms lasting at least 6 months. [2] Komaroff AL. Myalgic encephalomyelitis/chronic fatigue syndrome: a real illness. Ann Intern Med. 2015 Jun 16;162(12):871-2. http://annals.org/article.aspx?articleid=2322808 http://www.ncbi.nlm.nih.gov/pubmed/26075760?tool=bestpractice.com  The fatigue is not related to other medical or psychiatric conditions, and symptoms do not improve with sleep or rest.

Definitions of CFS/ME have evolved from a focus on fatigue and impairment as described in the US Centers for Disease Control (CDC) criteria, [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 to PEM/exertional exhaustion in ME/CFS as defined by the Canadian Consensus Criteria, [4] Carruthers BM, Jain AK, De Meirleir KL, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. 2003 [internet publication]. http://med.stanford.edu/content/dam/sm/chronicfatigue/documents/overview/CanadianCriteriaCFS2003.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 and systemic exertion intolerance disease (SEID) introduced in 2015 by the US National Academy of Medicine (then known as the Institute of Medicine [IOM]). SEID was defined based on an extensive review of the literature, and was introduced as an alternative term for CFS/ME 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. February 2015 [internet publication]. http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf [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 Diagnosis of SEID requires disabling fatigue, PEM, and unrefreshing sleep that are persistent, moderate or severe in severity, and present at least 50% of the time, plus either cognitive or orthostatic intolerance with the same severity and frequency. [6] Institute of Medicine of the National Academies. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. February 2015 [internet publication]. http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Pain was not considered unique to CFS/ME, and so was not included in the SEID criteria. Use of the term SEID is not currently widespread, and within this topic the nomenclature CFS/ME is used. These 3 definitions (CDC, Canadian Consensus Criteria, and National Academy of Medicine/IOM) have compatible criteria that focus on PEM, disability, sleep, pain, and cognition. [8] Jason LA, Evans M, Brown A, et al. Chronic fatigue syndrome versus sudden onset myalgic encephalomyelitis. J Prev Interv Community. 2015;43(1):62-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295655/ http://www.ncbi.nlm.nih.gov/pubmed/25584529?tool=bestpractice.com [9] Jason LA, Brown A, Clyne E, et al. Contrasting case definitions for chronic fatigue syndrome, myalgic encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis. Eval Health Prof. 2012 Sep;35(3):280-304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658447/ http://www.ncbi.nlm.nih.gov/pubmed/22158691?tool=bestpractice.com

PEM is the most characteristic feature of CFS/ME according to the National Academy of Medicine/IOM criteria. [6] Institute of Medicine of the National Academies. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. February 2015 [internet publication]. http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf [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. 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 with CFS/ME to make significant lifestyle changes to conserve their physical resources and mental concentration to stay competent in normal occupational, educational, and social settings. [10] 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 from the disorganised thoughts, total body pain, malaise, and other features of their chronic fatigue state. Consideration of 'fatigue' as mental or physical tiredness is too simplistic to encompass the scope of impairment in CFS/ME, and belies the inadequacy of the vocabulary of fatigue. There is a strong bias to the vocabulary of acute viral illness, such as influenza and poliomyelitis, because these were considered historical precedents of CFS/ME. [11] Sigurdsson B. Clinical findings six years after outbreak of Akureyri disease. Lancet. 1956 May 26;270(6926):766-7. http://www.ncbi.nlm.nih.gov/pubmed/13320872?tool=bestpractice.com

The World Health Organization classifies CFS/ME as a neurological illness. [12] World Health Organization. International classification of diseases 11th revision for mortality and morbidity statistics (ICD-11 MMS). 2018 [internet publication].  https://icd.who.int/browse11/l-m/en