Chronic Fatigue Syndrome Anthony James Cleare, Guy’s, King’s and St Thomas’ School of Medicine, London, UK Simon Wessely, Guy’s, King’s and St Thomas’ School of Medicine, London, UK Chronic fatigue syndrome represents an operationally defined condition with substantial, disabling and prolonged fatigue as its main symptom. It has a prevalence of about 1% and makes a substantial public health impact. Introduction The term chronic fatigue syndrome (CFS) is a new arrival on the medical scene, but it is not a new illness. The condition known to the Victorians as neurasthenia was clearly its forerunner, not just in terms of symptoms, but presumed aetiologies, treatments and much else. As neurasthenia gradually shifted from a physical to a psychological aetiology, its popularity declined, and the diagnosis had effectively vanished by the Second World War,exceptinpartsofAsia.CFSappearedinthe1980sin responsetoavarietyofevents,includingrenewedclaimsto havefoundaphysical,infectivecauseforillhealth,aseries of well publicized epidemic outbreaks, and the general change in doctor–patient relationships during this period. The term CFS and its variants are now widely used in the English-speaking and Scandinavian world, but not elsewhere. Pathophysiology of the Disease Biological factors Genetics Recent studies suggest that there is a genetic propensity to suffer from chronic fatigue: the concordance between monozygotic twins is more than twice that of dizygotic twins. Multivariate modelling suggests that part of this vulnerability is conferred through the genetic tendency to suffer from anxiety or depression, but that part is independent of psychiatric disorder. Viruses MostpatientsinwhomCFSisdiagnoseddatetheonsetof their symptoms to a viral infection, such as an upper respiratory tract infection or influenza. This led initially to greateffortstofindthevirusresponsibleforCFS,withthe assumption that CFS was due to a persistent viral infection. The history of that search has become clear: notwithstanding the many methodological problems in many of the studies, each new finding of an association with a particular virus has not been replicated in different populations or by different research groups. Researchers then returned to the original question: is CFS really associated with viral infections? This question was answered by a controlled prospective study involving 2000 subjects, half of whom had presented to their general practitioner with a symptomatic viral infection, and half for another reason (Wessely etal.,1995).Sixmonthslater, there was no difference in the rates of idiopathic chronic fatigue or CFS. On the other hand, those who ended up with chronic fatigue or CFS were more likely to have suffered previous fatigue or psychological distress before the viral infection. Thus, it seemed that the link between commonviralinfectionsandCFSwasmediatedbychance (the average person suffers four viral infections per year), selectiverecallandanattemptbypatientstomakesenseof their illness. However, other researchers thought that not all viral infections were the same. Different groups of researchers followed patients diagnosed with specific severe viral infections. There is now no doubt that some viruses are more likely to result in chronic fatigue than others. Table 1 shows the viruses identified to date. It is now clear that these are postviral effects, continuing after the acute viral infection has ceased, and that they affect a minority of subjectswhohavethevirus.Furtherstudyhasclarifiedthat thereareseveralsignificantfactorsincreasingtheriskofan individual suffering prolonged postviral fatigue. Thus, both previous psychiatric disorder and a prolonged Article Contents Secondary article . Introduction . Pathophysiology of the Disease . Frequency and Clinical Importance . Major Clinical Features and Complications . Approaches to Management . Summary Table 1 Fatigue following severe infections Rate of persistent fatigue 6months after diagnosis (%) Viral meningitis 25 Epstein–Barr virus glandular fever 16 Viral hepatitis 20 Q fever 42 a Common viruses 1 Baseline risk 1 a Controls also had a very high rate (26%) in this study. 1 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net