Mycoplasma and Chronic Fatigue Syndrome Question

In a very high percentage of my patients with chronic fatigue syndrome (CFS), I have noted a history of significant dental work (more than routine cleaning) during the 3 to 6 months before symptoms began. Because CFS may have a potentially infectious origin (or at least an infectious agent stimulating a neuroimmunologic disorder of the central nervous system), I was wondering if Mycoplasma fermentans is a common resident of the mouth, from which it might be disseminated by significant dental work?

Second, one of my patients with CFS had a sore throat that was so severe she almost seemed to have stridor. Her C1-esterase inhibitor was drawn and was low (8 mg/dL, with normal being 12-25 mg/dL). Repeat values were confirmatory. In a substantial percentage of subsequent patients with CFS, C1-esterase inhibitor levels were less than 12 mg/dL. Is there any potential relationship between a low level of a complement component inhibitor and CFS?

Steve Arthur, MD

Response from Robert I. Fox, MD, 05/08/01

Mycoplasma are present in the oral cavity and have been associated with accelerated periodontal disease in immunocompromised patients (eg, patients with HIV). It is highly likely that Mycoplasma will enter the bloodstream after dental procedures. However, the causal relationship of Mycoplasma and CFS remains controversial. In one study, certain strains of Mycoplasma were found by polymerase chain reaction (PCR) methods more frequently in CFS patients than in controls.[1] However, CFS patients did not show an antibody response to the Mycoplasma[2] and no organisms could be cultured. This suggests that Mycoplasma (or their nucleic acids) could be "innoculated" at the time of dental manipulation but that they are not immunogenic; the nucleic acids are subsequently detected by the very sensitive methods of PCR. As with other ubiquitous agents (eg, Epstein-Barr virus), the presence of the colonizing pathogen does not prove a causal relationship to a clinical syndrome.

Nevertheless, the potential role of Mycoplasma in CFS and other neurologic diseases remains unclear.[3,4]

The second question involves the potential finding of low complement levels or inhibitors of C1 esterase. There is one published study (in German) that reported low C1-esterase inhibitor levels, but this study used unusual detection methods. Because so many CFS patients have been screened for both C4- and C1-esterase inhibitor levels during the past 10 years, it seems unlikely that a high proportion of your patients would be low. I suspect that the detection assay in your laboratory is artifactually low.