Although diseases similar to chronic fatigue syndrome (CFS) have been recognized for centuries under various rubrics, strict diagnostic criteria for conditions dominated by medically unexplained chronic fatigue were first proposed in 1988. Current diagnostic criteria were crafted in 1994 by an International Chronic Fatigue Syndrome Study Group as an attempt to standardize patient populations included in research studies. The International CFS Re search Case Definition requires the presence of at least 6 months of persistent, unexplained fatigue that interferes with multiple domains of daily life, is not relieved by rest, and is accompanied by at least four of the following symptoms: cognitive impairment, sore throat, tender neck or lymph nodes, muscle pain, joint pain, headaches, unre-freshing sleep, and more than 24 hours of post-exertional malaise. Importantly, the research case definition precludes classification as CFS if a patient has an identifiable medical cause to be fatigued. Similarly, subjects with certain psychiatric conditions cannot be classified as CFS in research studies. Exclusionary psychiatric conditions include Schizophrenia, bipolar disorder, or melancholic major depression. It is important to realize that the CFS case definition was devised for research purposes, and the concept of exclusionary conditions is critical to avoid confounding CFS with other medical disorders. In clinical settings the list of exclusionary conditions is most useful as a list of differential diagnoses. In clinical practice, patients with various exclusionary conditions may also be diagnosed and managed as having CFS based on the physician's medical opinion.
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