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 neurologic 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 individualized 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.  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 characterized by a sudden or gradual onset of persistent disabling fatigue, postexertional 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.  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 Centers for Disease Control (CDC) criteria,  to PEM/exertional exhaustion in ME/CFS as defined by the Canadian Consensus Criteria,   and systemic exertion intolerance disease (SEID) introduced in 2015 by the 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 emphasize that dysfunction involves the entire body, and that it is aggravated by physical or cognitive exertion and other stressors.   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.  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.  
PEM is the most characteristic feature of CFS/ME according to the National Academy of Medicine/IOM criteria.   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.  Patients are often limited to a few hours per day of productive endeavors, with the remainder of the time spent resting with slow and partial recovery from the disorganized 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. 
The World Health Organization classifies CFS/ME as a neurologic illness. 
Division of Rheumatology, Immunology, and Allergy
JNB declares that he has no competing interests.
Dr James N. Baraniuk would like to gratefully acknowledge Dr Craig N. Sawchuk and Dr Dedra Buchwald, previous contributors to this topic. CNS declares that he has no competing interests. DB is an author of a number of references cited in this topic. This topic was reviewed in 2018 by a patient with CFS/ME, and their feedback was considered as part of the topic update. The patient peer reviewer does not wish to be named.
Consultant Psychiatrist in Psychological Medicine
South London and Maudsley NHS Foundation Trust
AS declares that he was a guideline development group member for NICE CFS/ME 2007 guidelines CG53.
Professor of Pediatrics
Division of Infectious Diseases
Northwestern University Feinberg School of Medicine
Ann & Robert H. Lurie Children’s Hospital of Chicago
BZK declares that he has no competing interests.
Associated Professor in Rehabilitation Medicine
Department of Clinical Sciences
Danderyd University Hospital
IB-L declares that he has no competing interests.
Consultant Physician in Rehabilitation Medicine
Wrightington, Wigan and Leigh NHS Trust
TG declares that he has no competing interests.
ME patient advocate
Emeritus Professor of Medicinal Chemistry
University of Sunderland
MH has lectured on ME and made national and international presentations to groups concerned with ME in Denmark, Sweden, Australia, US, and UK. He has acted as a witness for the GMC (UK) and received payment for this (travel and subsistence). He has also received payment from a family he supported in legal proceedings relating to vaccine damage, after the case was settled in their favor. He is a founder member of the Academy Of Nutritional Medicine, which has a special interest in Lyme disease. Their guidelines mention ME/CFS several times. He has given their keynote address for 3 years. He is the author of the paper Hooper M. Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research. J Clin Pathol. 2007;60:466-71. He is a member of the trustees for the John Richardson Research Group and the ME research group. He is also a trustee of European Services for People with Autism (ESPA) and a member of ESPA-Research, which is developing techniques to help with this condition. All of this work is voluntary.
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