Introduction Myalgic encephalomyelitis (ME)
Chronic fatigue syndrome-the CDC definition
CFS-the Australian definition
CFS-the British definition
CFS-the international definition (also known as the Fukuda or research definition)
Myalgic encephalomyelitis/CFS-the Canadian definition
The international definition revisited
- New onset of persistent or relapsing, debilitating fatigue or easy fatigability in a person who has no previous history of similar symptoms, that does not resolve with bed rest, and that is severe enough to reduce or impair average daily activity below 50 percent of the patient’s premorbid activity level for a period of at least 6 months
- Exclusion of other clinical conditions that may produce similar symptoms (e.g., malignancy, autoimmune disease, chronic psychiatric disease, and chronic inflammatory disease, among others)
- Mild fever
- Sore throat
- Painful lymph nodes in the anterior or posterior cervical or axillary distribution
- Unexplained generalized muscle weakness
- Muscle discomfort or myalgia
- Prolonged ( ≥ 24 hours) generalized fatigue after exercise
- Generalized headaches
- Migratory arthralgia without joint swelling or redness
- Neuropsychologic complaints
- Sleep disturbance
- Low-grade fever
- Nonexudative pharyngitis
- Chronic persisting or relapsing fatigue of a generalized nature, exacerbated by minor exercise, causing significant disruption of usual daily activities, and present for more than 6 months
- Neuropsychiatric dysfunction including impairment of concentration evidenced by difficulty in completing mental tasks which were easily accomplished before the onset of the syndrome; new onset of short term memory impairment
- No alternative diagnosis reached by history, physical examination, or investigations over a 6-month period
Source: Lloyd, A.R., Hickie, I., Boughton, D.R., Spencer, O., & Wakefield, D. (1990). Prevalence of chronic fatigue syndrome in an Australian population. The Medical Journal of Australia, 153, 522-528.
The "Oxford criteria" defined two broad syndromes: chronic fatigue syndrome and post-infectious fatigue syndrome (PIFS). CFS was defined by the following characteristics:
- Fatigue is the principal symptom.
- It is a syndrome of definite onset that is not lifelong.
- Fatigue is severe, disabling, and affects physical and mental functioning.
- Fatigue has been present for a minimum of 6 months, during which it was present for more than 50 percent of the time.
- Other symptoms may be present, particularly myalgia, mood, and sleep disturbance.
- Exclusion criteria included patients with established medical conditions known to produce chronic fatigue and those with certain psychiatric disorders (substance abuse, eating disorders, organic brain disease).
PIFS was considered a subtype of CFS that either follows an infection or is associated with a current infection. PIFS fulfills all the criteria for CFS as well as the following:
- Definite evidence of infection at onset or presentation
- Present for a minimum of 6 months after onset of infection
- Infection corroborated by laboratory evidence
Source: Sharpe, M.C., Archard, L.C., Banatvala, J.E., Borysiewica, L.K., Clare, A.W., David, A., et al. (1991). A report—chronic fatigue syndrome: Guidelines for research. Journal of the Royal Society of Medicine,84, 118-121.
This revision of the 1988 CDC case definition remains the currently the accepted research definition, also known as the Fukuda definition, and was based on the presence of the following:
- Clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is of new or definite onset (has not been lifelong); is not the result of ongoing exertion; is not substantially alleviated by rest; and results in substantial reduction in previous levels of occupational, educational, social, or personal activities
- The concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or more
consecutive months of illness and must not have predated the fatigue:
- Self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities
- Tender cervical or axillary lymph nodes
- Muscle pain, multijoint pain without joint swelling or redness
- Headaches of a new type, pattern, or severity
- Unrefreshing sleep
- Postexertional malaise lasting more than 24 hours
Source: Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., & Komaroff, A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of Internal Medicine, 121 (12):953-959.
- Fatigue: Significant degree of new-onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level.
- Post-exertional malaise and/or fatigue: Loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional fatigue, malaise and/or pain, and a tendency for other symptoms to worsen. A pathologically slow recovery period (more than 24 hours).
- Sleep dysfunction: Unrefreshing sleep or poor sleep quality; rhythm disturbance such as reversed or chaotic diurnal sleep rhythms.
- Pain: Significant degree of myalgia experienced in muscles and/or joints; often widespread and migratory in nature. Often, significant headaches of new type, pattern, or severity.
- Neurological/cognitive manifestations: Two or more of the following: confusion; impairment of concentration and short-term memory consolidation; disorientation; difficulty with information processing, categorizing, and word retrieval; and perceptual/sensory disturbances. Possible cognitive or sensory overload (e.g., photophobia, hypersensitivity to noise) and/or emotional overload leading to relapses.
- At least one symptom from two of the following categories:
- Autonomic manifestations: Orthostatic intolerance, light-headedness, extreme pallor, nausea and irritable bowel syndrome, urinary frequency and bladder dysfunction, palpitations with or without cardiac arrhythmia, exertional dyspnea.
- Neuroendocrine manifestations: Loss of thermostatic stability, heat/cold intolerance, marked weight change, loss of adaptability and worsening of symptoms with stress.
- Immune manifestations: Tender lymph nodes; recurrent sore throat; flu-like symptoms; general malaise; new sensitivities to food, medications, and/or chemicals.
- Illness persisting for at least 6 months. Usually acute onset, but may be gradual.
Source: Carruthers, D.M., Jain, A.K., De Meirleir, K.L., Peterson, D.L., Klimas, N.G., Lerner, A.M., et al. (2003). Myalgic encephalomyelitis/chronic fatigue syndrome: Clinical working case definition, diagnostic and treatment protocols. Journal of Chronic Fatigue Syndrome, 11 (1):7-115.
The 1988 case definition offered examples of conditions that would preclude a diagnosis of CFS, such as malignancy, autoimmune disease, chronic psychiatric disease, and chronic inflammatory disease. The International Chronic Fatigue Syndrome Study Group elaborated on these exclusionary criteria to include:
- Permanent medical exclusions:
- Organ failure (e.g., emphysema, cirrhosis, cardiac failure, chronic renal failure)
- Chronic infections (e.g., AIDS, hepatitis B or C)
- Rheumatic and chronic inflammatory diseases (e.g., systemic lupus erythematosis, Sjorgren’s syndrome, rheumatoid arthritis, inflammatory bowel disease, chronic pancreatitis)
- Major neurologic diseases (e.g., multiple sclerosis, neuromuscular diseases, epilepsy or other diseases requiring ongoing medication that could cause fatigue, stroke, head injury with residual neurologic deficits)
- Diseases requiring systemic treatment (e.g., organ or bone marrow transplantation; systemic chemotherapy; radiation of brain, thorax, abdomen, or pelvis)
- Major endocrine diseases (e.g., hypopituitarism, adrenal insufficiency)
- Primary sleep disorders (e.g., sleep apnea, narcolepsy)
- Temporary medical exclusions:
- Conditions discovered at onset or initial evaluation (e.g., effects of medications, sleep deprivation, untreated hypothyroidism, untreated or unstable diabetes mellitus, active infection)
- Conditions that resolved (e.g., pregnancy until 3 months post-partum, breastfeeding, major surgery until 6 months post-operation, minor surgery until 3 months post-operation, major infections such as sepsis or pneumonia until 3 months post-resolution)
- Major conditions whose resolution may be unclear for at least 5 years (e.g., myocardial infarction, heart failure)
- Morbid obesity (body mass index > 40)
- Permanent psychiatric exclusions:
Lifetime diagnoses of bipolar affective disorders, schizophrenia of any subtype, delusional disorders of any subtype, dementias of any subtype, organic brain disorders, and alcohol or substance abuse within 2 years before onset of the fatiguing illness
Source: Reeves, W.C., Lloyd, A., Vernon, S.D., Klimas, N., Jason, L.A., Bleijenberg, G., et al. and the International Chronic Fatigue Syndrome Study Group. (2003). Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Services Research, 3 (25).