Neither a specific cause(s) nor any specific diagnostic test(s) have been identified for this illness. The range of symptoms, however, suggests there may be subtle perturbations in multiple physiological pathways that are triggered by diverse causes such as infection, stress, brain structure abnormalities, hormone levels, proinflammatory cytokines, etc. Epidemiological evidence is also limited and requires further study. Existing data suggest, however, that CFS occurs three to four times more frequently among women than among men and 10 times more often in white Americans than in Americans of other racial/ethnic groups. A more recent study disputes these numbers and would narrow the gap between the sexes, as well as among racial/ethnic population subgroups.
The cluster of symptoms we know as CFS has been described over the years under many names with varying definitions and suspected causes. But it was not until 1988 that a formal case definition emerged. A brief historical account follows.
Epstein-Barr virus syndrome
In the early 1980s, patients with symptoms including fatigue, muscle pain, and depression were often diagnosed with chronic Epstein-Barr virus syndrome or chronic mononucleosis syndrome. [ 1 ]
These patients had symptoms that suggested infection, such as low-grade fever, recurrent sore throat, and tender lymph nodes. Epstein-Barr virus (EBV), which causes acute mononucleosis, was considered a likely source. But researchers could not isolate EBV as the cause of the syndrome and, as yet, have not definitively identified any other infectious agents. Chronic fatigue syndromea formal case definition from the United States
In 1988, in an effort to standardize research definitions, a group of experts led by the Centers for Disease Control and Prevention (CDC) proposed a new name for Epstein-Barr virus syndrome that more accurately described it: chronic fatigue syndrome. [ 2 ]
The new definition outlined two major criteria:
- Persistent or relapsing, debilitating fatigue, lasting at least 6 months, in a person who has no previous history of similar symptoms; and
- Exclusion of other clinical conditions that may produce similar symptoms (e.g., malignancy, autoimmune disease, chronic psychiatric disease, and chronic inflammatory disease, among others).
The definition also included the occurrence of at least eight symptoms including mild fever, sore throat, painful lymph nodes, prolonged fatigue after exercise, joint or muscle pain, unexplained muscle weakness, headaches, and sleep disturbance.
CFSthe Australian definition
At the same time as CDC's effort, researchers in Australia
developed their own case definition of CFS. [ 3 ]
The Australian definition captured CDCs major criteria, and added the symptom of neuropsychiatric dysfunction, which included impairment of concentration and short term memory.
CFSthe British definition
A 1990 consensus meeting of researchers in Great Britain
found neither of these definitions satisfactory in practice. [ 4 ]
The resulting guidelines included a glossary describing in detail the principal symptoms of fatigue, disability, mood disturbance, myalgia (muscle pain), and sleep disturbance. The Oxford criteria, as they came to be known, also defined post-infectious fatigue syndrome (PIFS), a subtype of CFS that either follows an infection or is associated with a current infection. CFSthe International definition
In response to criticisms of the original CDC definition of CFS as too ambiguous and over-exclusive, and to facilitate a more systematic collection of data internationally, the International Chronic Fatigue Syndrome Study Group,
headed by CDC and including representatives from Australia and Great Britain, proposed a revised CFS case definition in 1994. [ 5 ]
Known as the Fukuda or research definition, it was based on the presence of the following:
Myalgic Encephalomyelitis (ME)/CFSthe Canadian definition
- 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
An expert consensus panel convened in Canada in 2001 and developed a case definition of ME/CFS designed for clinical diagnoses, rather than for research purposes as was the 1994 definition of CFS.[ 6 ]
The panel outlined criteria for the symptom categories of fatigue; post-exertional malaise or fatigue; sleep dysfunction; pain; and body system manifestations including neurological/cognitive (e.g., difficulties with memory or concentration), autonomic (e.g., vertigo), neuroendocrine (e.g., heat or cold intolerance), and immune (e.g., sore throat). The international CFS definition revisited
In 2003, the international study group revisited the 1994 case definition of CFS to identify and address ambiguities, with the goal of facilitating future research. [ 7 ]
The original definition offered examples of conditions that would preclude a diagnoses of CFS. The study group elaborated on these exclusionary criteria, and recommended the use of several specific standardized instruments in assessing fatigue and accompanying symptoms.