From a look at Table 1 you can see a significant change in the definitions from Holmes and Fukuda to the CCC 2003. This was the first definition to incorporate CFS with the Myalgic Encephalomyelitis (ME) definition by Dr Ramsay several decades earlier. This definition requires post-exertional malaise (PEM), fatigue, pain, sleep disturbance, a couple neurocognitive issues and symptoms from the immune, endocrine and autonomic systems.

This diagnosis emphasized the multi-system component of the illness and attempted to homogenize the cohort diagnosed by requiring several specific symptoms. One of those specific symptoms, PEM, is clearly the most distinguishing feature of ME / CFS.