• Peter Denton White.
• Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
• J Eval Clin Pract. 2019 Dec 1; 25 (6): 991-996.

The causes of chronic fatigue syndrome (CFS) remain unknown, with many failures to replicate new findings. This may be because the condition is hard to diagnose, difficult to classify, or because of its heterogeneous nature. Authors have problems in differentiating CFS from myalgic encephalomyelitis (ME), which leads many to label it as a hybrid CFS/ME or ME/CFS. Attempts to validate the many published criterion-based definitions have ended in failure. The International Classification of Diseases provide several different descriptions to choose from, although the latest 11th edition has narrowed this down. This paper describes conventional attempts to define and classify the illness, suggesting that this may be what leads to a failure to replicate putative causes. The approach to CFS/ME may require a shift in the assumption that the illness is homogeneous. An alternative approach is provided by studies suggesting that the condition is heterogeneous. ConclusionThe way forward may be to be over-inclusive regarding the diagnosis as a first step, while subdividing the condition into likely subgroups as a means of finding valid and reliable associations with potential causes. Studies of aetiology must involve prospective designs since cross-sectional studies cannot inform either aetiology or pathophysiology.© 2019 John Wiley & Sons, Ltd.

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