Criteria

A complicating factor in ME/CFS is the presence of 9 sets of subjective clinical criteria.

Key sets of criteria are listed here; see the Differences in diagnostic criteria section in Diagnostic approach.

UK National Institute for Health and Care Excellence (NICE)[8]

The 2021 NICE guideline on the diagnosis and management of ME/CFS addresses the continuing debate surrounding the best approach for the diagnosis and management of ME/CFS. The guideline suggests that a diagnosis of ME/CFS should be suspected if a person has all the following symptoms present:

  • Debilitating fatigue that is worsened by activity; is not caused by excessive cognitive, physical, emotional, or social exertion; and is not significantly relieved by rest.

  • Post-exertional malaise (PEM) in which the worsening of symptoms is often delayed in onset by hours or days; is disproportionate to the activity; and has a prolonged recovery time that may last hours, days, weeks, or longer.

  • Unrefreshing sleep or sleep disturbances (or both), which may include feeling exhausted; feeling flu-like and stiff on waking; and broken or shallow sleep, altered sleep patterns, or hypersomnia.

  • Cognitive difficulties, which may include problems finding words or numbers, difficulty in speaking, slowed responsiveness, short-term memory problems, and difficulty concentrating or multitasking.

It is necessary that the above symptoms are present for a minimum of 6 weeks in adults and 4 weeks in children and young people.[8]

US Institute of Medicine (IOM; now the National Academy of Medicine) 2015 diagnostic criteria for ME/CFS[6]

In 2013, the IOM performed a comprehensive analysis of the literature with expert consultation and proposed the term "systemic exertion intolerance disease" (SEID) together with new diagnostic criteria.

A diagnosis of ME/CFS/SEID is made if patients have the following 3 symptoms:

  • Substantial reduction/impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities that persists for more than 6 months; is accompanied by fatigue that is often profound; is of new or definite onset; is not the result of ongoing excessive exertion; and is not substantially alleviated by rest

  • PEM

  • Unrefreshing sleep

Patients are also required to have at least 1 of the following symptoms:

  • Cognitive impairment

  • Orthostatic intolerance

Symptoms must be present at least half of the time and have moderate, substantial, or severe intensity.

Pain symptoms and systemic hyperalgesia were not included in the IOM criteria due to insufficient published data in ME/CFS. However, it was noted that pain is a common symptom of ME/CFS along with headaches of a new type and pattern; swollen or tender lymph nodes; sore throat; visual disturbances; nausea; and allergies or sensitivities to foods, odors, chemicals, or medications.

International Consensus Criteria (ICC; 2011)[93]

According to the ICC criteria, published in 2011, ME/CFS is an acquired neurologic disease with multisystemic dysfunctions. Diagnosis requires:

  • Post-exertional neuroimmune exhaustion (PENE; compulsory feature) characterized by marked, rapid physical and/or cognitive fatigability in response to exertion; post-exertional symptom exacerbation; post-exertional exhaustion; prolonged recovery period; and/or low threshold of physical and mental fatigability resulting in a substantial reduction in pre-illness activity levels.

  • Neurologic impairments (at least 1 symptom from 3 of the following symptom categories): (a) neurocognitive impairments (difficulty processing information; short-term memory loss); (b) pain (headaches; noninflammatory somatic pain); (c) sleep disturbance (disturbed sleep patterns; unrefreshing sleep); and (d) neurosensory, perceptual, and motor disturbances (inability to focus; sensory defensiveness; muscle weakness).

  • Immune, gastrointestinal, and genitourinary impairments (at least 1 symptom from the following 5 symptom categories): (a) recurrent or chronic flu-like symptoms that worsen with exertion; (b) susceptibility to viral infections with prolonged recovery periods; (c) gastrointestinal tract difficulties; (d) genitourinary problems; and (e) sensitivities to food, medications, odors, or chemicals.

  • Energy production/transportation symptoms (at least 1 symptom from the following): (a) cardiovascular intolerance; (b) respiratory difficulties; (c) loss of thermostatic stability; and (d) intolerance of extreme temperature.

Canadian Consensus Criteria (CCC) for myalgic encephalomyelitis (ME/CFS) (2003, revised 2010)[4][5]

These criteria define persistent or recurring chronic fatigue as lasting for over 6 months, but not a lifetime. Impairment includes substantial reductions in occupational, educational, social, and personal activities compared with before the fatigue started. Classic ME/CFS symptoms listed below persist or recur during the prior 6 months of illness. Symptoms may predate the reported onset of fatigue.

  • PEM, fatigue, or exhaustion. The activity or exertion causing problems may be relatively mild, such as walking up a flight of stairs, using a computer, or reading a book. It does not have to be strenuous exercise. There must be a loss of physical stamina, loss of mental stamina, rapid or sudden muscle fatigue, cognitive fatigue, post-exertional malaise and/or fatigue, and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. The recovery is slow, often taking 2-24 hours or longer.

  • Unrefreshing sleep is present with problems of sleep quantity (e.g., inability to fall asleep, early awakening, or prolonged sleep) and rhythm disturbance (e.g., day/night reversal or frequent naps).

  • Pain (or discomfort) that is widespread and migratory in nature, and manifests as achy and sore muscles. Myofascial pain, arthralgia, and stiffness are present in more than one joint but erythema, edema, or other signs of inflammation are absent. Visceral pain includes noncardiac chest pain (e.g., costochondritis, esophageal spasm) or epigastric, periumbilical, pelvic, or other abdominal pain. Headaches are more frequent and severe than prior to onset of the fatigue. Migraine is common, with localization behind the eyes or in the back of the head, and with associated severe photophobia, phonophobia, nausea, or emesis that is exacerbated by usual daily activities; avoidance behaviors include lying in a dark, quiet room.

Two or more of the following neurologic/cognitive manifestations are required:

  • Impaired short-term memory (self-reported, or observed difficulty recalling information or events)

  • Difficulty maintaining focused attention; disturbed concentration may impair ability to remain on task or to screen out extraneous/excessive stimuli

  • Loss of visual depth perception

  • Difficulty finding the right word

  • Frequently forget what wanted to say

  • Absentmindedness

  • Slowness of thought

  • Difficulty recalling information

  • Need to focus on one thing at a time

  • Trouble expressing thought

  • Difficulty comprehending information

  • Frequent loss of train of thought

  • Sensitivity to bright lights or noise

  • Muscle weakness/muscle twitches

At least one symptom from two of the following three categories:

  • Orthostatic and visceral manifestations: complaints of dizziness or fainting; feeling unsteady when standing up; disturbed balance; or palpitations with or without cardiac arrhythmias. Positive tilt-table test for postural orthostatic tachycardia or neurally mediated hypotension. Shortness of breath, nausea, irritable bowel syndrome, or bladder pain.

  • Thermal instability and appetite: recurrent feelings of feverishness and cold extremities; sweating episodes; intolerance of extremes of heat and cold; or documentation of subnormal body temperature. There may be marked changes in weight and/or appetite.

  • Interoceptive manifestations: recurrent flu-like symptoms; repeated feverishness and sweats; nonexudative sore or scratchy throat; lymph nodes tender to palpitation with minimal or no swelling; or chemical irritant sensitivities to food, odors, or chemicals (nonallergic rhinopathy).

Additionally, there is a severity spectrum to ME/CFS as follows:

  • Mild ME/CFS: defined by a 50% reduction in pre-illness activity level, patients are still mobile; however, report reduced work or other activities.

  • Moderate ME/CFS: defined by a reduction in mobility with significant restrictions to activities of daily living and needs very frequent rest.

  • Severe ME/CFS: defined as housebound patients with limited activities of daily living.

  • Very severe ME/CFS: defined as mostly bedridden and unable to undertake activities of daily living independently.

The CCC were revised in 2010 with added requirements regarding the severity and frequency of symptoms (e.g., under the revised criteria, a symptom must be present with at least moderate severity about half of the time in order to meet the criteria for a particular symptom category).[5]

1994 US Centers for Disease Control and Prevention (CDC; "Fukuda") criteria[3]

The 1994 CDC diagnostic criteria for chronic fatigue syndrome include the following:

Clinically evaluated, unexplained, persistent or relapsing fatigue lasting at least 6 months. The fatigue is not the result of ongoing physical exertion, with resting, sleeping, and downgrading activity being nonrestorative. The fatigue causes significant impairment in personal, social, and/or occupational domains, and represents a substantial reduction in premorbid levels of activity and functional capacity.

The concurrent presence of at least 4 of the following symptoms over a 6-month period:

  • Impaired short-term memory or concentration

  • Sore throat

  • Tender lymph nodes/glands

  • Muscular pain

  • Joint pain in multiple areas

  • New-onset headaches

  • Unrefreshing sleep

  • PEM/fatigue lasting longer than 24 hours

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