Causes of Chronic Fatigue Syndrome

The cause of chronic fatigue syndrome (CFS) remains unknown. While a single cause may yet be identified, there is growing consensus in the medical community that CFS is most likely a common endpoint of many differing etiologic agents including a multitude of potential causes that range from infectious agents to various toxic exposures and to trauma both physical or emotional.

Historically, the conditions that were described in the past that most resemble CFS have seemingly followed a variety of known and unknown epidemics due to infectious diseases. Indeed, protracted mononucleosis would easily fit the CDC case definition as would what is called chronic Lyme disease.

However, patients with post-traumatic stress disorder and Gulf War Syndrome which may be due in part to toxic exposure and prolonged stress also can fit the case definition of CFS.

If CFS is a final common pathway then what exactly is that pathway? Consensus has begun to develop around dysregulated neurohormonal pathways and disturbances in immune regulation. The immune system appears to be chronically activated and there appears to be a disorder of one or more neuroendocrine pathways within the hypothalamus that may be either the cause of disordered immunity or a reflection of it.

A possible synthesis of these observations could come from the realization that herpes-group viruses, which can activate at any time and under a variety of different stressors, might allow for the appearance of a post-infectious syndrome that seems to erupt following trauma, stress or even a toxic exposure.

Regardless of etiology and perhaps the primary mediators of this illness which include immune activation related cytokines and their downstream effects as well as a disorder of hypothalamic function, there remains the mystery of why the system cannot recover and why chronic illness is so profoundly expressed in these patients.

In other words, beyond etiology and the mediators of illness, why is the system stalled for no discernible reason? While there is no final answer, there is at least the framing of a question.

There is also near certainty that there is a profound change in the normal phenotypic expression of genes in CFS. Perhaps that is where leverage on reversing this disturbed process lies.