Etiology

Although no one simple cause is responsible for ME/CFS, there is emerging evidence that a number of infections can trigger and possibly perpetuate the symptoms of CFS. The initial infection can create an imbalance of the immune system, which allows the persistence of the offending virus and also may reactivate pre-existing DNA viruses such as Varicella-Zoster virus (the cause of shingles). Chemical agents and vaccinations have been reported to trigger the disease process as well.

Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human herpes virus 6 (HHV-6), Chlamydia pneumoniae, Parvovirus B19, Q fever, Brucella species, Toxoplasma and Borrelia burgdorferi (the cause of Lyme’s disease) have all been reported to cause CFS in a small number of patients.

Based on the research done in the United Kingdom, Enterovirus (EV, Coxsackievirus B and Echoviruses) are clearly important trigger/causes of the disorder. Viral genome (RNA) was found in the blood and in the muscles of ME/CFS patients by several researchers, although the NIH investigator could not reproduce the same results. The discrepancy in results led to a shift of the paradigm in ME/CFS in the mid-1990s.

During and after initial infection, viruses often hide in our body by manipulating our finely orchestrated immune system and vulnerable cells. Animal research has demonstrated the presence of stable viral genome in cells long after the initial infection, but the “true viral particle” is difficult to isolate. Once viral persistence is established and protected by our own cells, the immune response can only react to these viral parasites with futility, causing continuous or cyclical symptoms of CFS. Virus “hide and seek” may be the reason why different researchers could not consistently demonstrate the infectious agents.

By carefully evaluating 600 ME/CFS patients over the last 6 years, our center demonstrated that various infectious agents could cause the common symptoms of ME/CFS. Similar to the European studies, our recent data suggests that Enterovirus (EV) could be a major trigger/cause among the diverse etiologies for ME/CFS. Our studies confirmed EV RNA sequence in the peripheral white blood cells taken from CFS/ME patients, and the relative frequency of RNA detection correlated with the severity of symptoms. In addition, administration of α-interferon and ribavirin or the combination of α-and γ-interferon to CFS/ME patients with persistent EV infection resulted in significant improvement of clinical symptoms and suppression of EV RNA. Symptomatic relapses and reappearance of EV RNA in white blood cells after drug discontinuation lend support to the pathogenic role of EV in these patients. Demonstration of EV capsid protein 1 in 82% of stomach biopsies taken from more than 300 CFS/ME patients, and the finding of EV RNA and the growth of non-cytopathic EV (viruses chronically living inside the cells) in the same tissues provided compelling evidence for persistent EV infection.

A number of physiological, endocrine and neurological phenomena (i.e. neuro-cardiogenic hypotension, brain-pituitary-adrenal axis dysfunction sleep disorder and depression) have been described. These may only be different manifestation of the disease rather than the root of the problem. Dysfunctions of different components of the immune systems have been well documented in CFS patients, but the cause-effect relationship is still not established.