Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) 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 (ME/CFS) as a neurologic illness.
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 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.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is more than fatigue. Up to 30.5% of the population have chronic fatigue that may be part of another disease or idiopathic in nature. Therefore, it is essential to carefully apply appropriate, modern diagnostic criteria and search for exclusionary conditions when evaluating a patient with prolonged, unremitting, and disabling fatigue.
There are several diagnostic criteria for ME/CFS 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, as well as pejorative. The term "myalgic encephalomyelitis" is also problematic, given the limited evidence for brain inflammation.
ME/CFS 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. PEM may be better explained as exertional exhaustion or a general increase in the patients' spectrum of symptoms after minimal effort above their usual. Prevalence in Europe is estimated at 0.2% to 2%.
Definitions of ME/CFS 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 (CCC), 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 ME/CFS 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 ME/CFS, and so was not included in the SEID criteria. Use of the term SEID is not currently widespread, and within this topic the nomenclature ME/CFS is used. The UK National Institute for Health and Care Excellence guidance does not attempt to redefine ME/CFS, but does include a strong statement for the requirement of PEM during diagnosis, and concern about postexertional symptoms during treatment. These three definitions (CDC, CCC, 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 ME/CFS 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 ME/CFS 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 ME/CFS, 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 ME/CFS.
The World Health Organization classifies ME/CFS as a neurologic illness.
History and exam
Key diagnostic factors
- persistent disabling fatigue
- postexertional malaise/fatigue (PEM), exertional exhaustion
- short-term memory and/or concentration impairment
- sore throat
- generalized arthralgia without inflammation
- headache/migraine with onset after the fatigue
- unrefreshing sleep
- orthostatic intolerance
- diffuse muscular, tendon, fascial, and other pain
- tender lymph nodes
Other diagnostic factors
- age of onset (adolescence and 30 to 50 years)
- flu-like symptoms (malaise, myalgia, feverishness)
- anxiety, affective disorder, atypical depression
- sensations of altered temperature
- exertion-induced cognitive dysfunction (affecting working memory, not persistent)
- irritant sensitivities
- female sex
- Epstein-Barr infection in adolescents
- coronavirus disease 2019 (COVID-19)
- positive family history of ME/CFS
- genetic factors
- specific infectious diseases in adults
- gut microbiome
- psychological factors
- major depressive disorder
- joint hypermobility/laxity
1st investigations to order
- DePaul symptom questionnaire
- CBC with WBC differential
- erythrocyte sedimentation rate
- comprehensive metabolic panel
- thyroid-stimulating hormone
- antinuclear antibody (ANA), rheumatoid factor
- HIV antibody test
Investigations to consider
- heads-up tilt-table test if symptomatic orthostatic intolerance
- serum ferritin
- urine toxicology screen
- antibody tests for gluten sensitivity/coeliac disease
- 2-day cardiopulmonary exercise testing
- Coronavirus disease (COVID-19)
- Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management
- Myalgic encephalomyelitis/chronic fatigue syndrome: symptoms and diagnosis of ME/CFS
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