Etiology of ME/CFS Model of Pathogenesis

The etiology of ME/CFS remains poorly defined, different - not necessarily consistent - case definitions for ME/CFS have been proposed and overlapping syndromes, such as fibromyalgia, myofascial pain syndrome, multiple chemical sensitivities, irritable bowel syndrome and interstitial cystitis, may pose a diagnostic challenge to patients and their health care providers. Considerable heterogeneity in the clinical presentation of ME/CFS does exist from one patient to the next and no single model will describe every individual case of ME/CFS. There have, however, been significant advances in our understanding of the pathogenesis of ME/CFS in recent years.

Accordingly, the following model of pathogenesis applies to a majority of patients accurately diagnosed as having chronic fatigue syndrome:

  1. ME/CFS is an immune-mediated illness with immune activation or dysfunction resulting from a number of possible root causes, including triggers by infectious agents, environmental sensitivities, genetic factors and/or physical stressors. The initiating cause of the immune activation or dysfunction in ME/CFS is often quite difficult to determine and remains unknown.
  2. The symptoms of ME/CFS result largely from involvement of the central nervous system, including the neuro-endocrine and autonomic nervous systems, and alterations in cognition, sleep physiology, pain sensing pathways and neurotransmitter functions.
  3. The cause of fatigue in ME/CFS is poorly understood, but probably results from a combination of dysfunction of the central nervous system, the immune system, the neuroendocrine system and abnormalities of metabolic regulation.
  4. ME/CFS is not primarily a psychological illness. However, many patients and their families may benefit from general, supportive psychological interventions to help them cope with the emotional effects of such a devastating, poorly understood chronic illness and to guide them through their efforts at rehabilitation and adaptation.