Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME), is a challenge to physicians. CFS prevalence is below 1 % in a general population. There are no convincing models that might explain etiology and pathogenesis of CFS as an independent, unique disease. No consistent diagnostic criteria are available. In the differential diagnosis of chronic fatigue, a variety of somatic (e. g. chronic infectious diseases, multiple sclerosis, endocrinological disorders) and psychiatric/psychosomatic diseases should be considered. After exclusion of somatic causes, there is a significant overlap with major depression and somatoform disorders. Exercise therapy, antidepressants and psychotherapy are useful treatment options. Unless there is enough evidence for neuroinflammation, aggressive immunotherapies like rituximab should not be considered. In sum, there is not enough evidence to assume that CFS is an independent, unique disease.
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