Chronic Fatigue Syndrome
Abstract & Commentary
By Joseph F. John, MD, FACP, FIDSA, FSHEA, Associate Chief of Staff for Education, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, is Associate Editor for Infectious Disease Alert.
Dr. John is a consultant for Cubist, Genzyme, and bioMerieux, and is on the speaker's bureau for Cubist, GSK, Merck, Bayer, and Wyeth.
Synopsis: A group of investigators reports the detection of enteroviral antigen in gastric antral parietal cells of 82% of patients with chronic fatigue syndrome and 20% of controls, but the virus was not recovered in culture.
Sources: Chia JKS, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008;61:43-48; Klimas NG, Koneru AO. Chronic fatigue syndrome: Inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep. 2007;9:482-487.
The etiology of chronic fatigue syndrome (CFS) remains conjectural. There are broad-based immune deficiencies in some patients with CFS. There is still skepticism about the existence of the entity, but recent genomic studies of patients diagnosed with CFS suggest there is a predisposition to the disease. There are relatively firm criteria of the illness, as determined by the CDC.
Many patients with CFS have persisting gastrointestinal complaints, from persistent diarrhea, obstipation, to frank constipation. Motility problems seem to plague these patients. Now workers from EV Medical Research in Lomita, California, have published data that there is an association with an enterovirus infection of the stomach in patients with CFS. The authors took 165 patients with CFS and did antral biopsies, and stained these biopsies with specific monoclonal antibody for an enterovirus-specific viral capsid protein (VP1). Further testing was performed to show that the antibody uptake was specific. RT-PCR was also performed on RNA extracted from gastric samples. Viral cultures for enterovirus were also performed.
The study reported that 82% of biopsies were positive for VP1 within parietal cells, whereas only 20% of control biopsies were positive. These workers even kept biopsies form six CFS patients at the onset of their disease two to eight years previously, and showed that there was persistent staining for VP1. RNA was detected in 37% of 24 samples. Viral cultures were problematic, but did reveal growth of enterovirus in cells treated with 5-idu and dexamethasone, but growth at four weeks often disappeared at eight weeks.
Commentary
This paper is from the pathology literature, and we do not learn much about the patients nor their severity of disease, except to know that they all had gastrointestinal symptoms associated with their CFS. In the Results section, we also learn that the more (2+) staining of the gastric mucosa was associated with greater ability to perform sedentary work than patients with less staining. (P = 0.016 by Fisher exact test). Many of these patients had evidence of chronic inflammation on endoscopic biopsy. Only a few had H. pylori colonization. In six patients, enteroviral protein was detected in stomach biopsy before CFS began. The authors emphasize that since there are many 70 serotypes of enteroviruses, reinfection may also be common in these patients.
It is troubling that more culture positivity was not seen in this series, but enteroviruses can be fussy about growing in some standard cell lines, thus the perturbing of the cultures with 5-idu and steroid encouraged growth. Optimal conditions for growth certainly need to be established. Indeed, after the authors obtained enteroviral growth on some early samples, they state that they obtained no growth on the next 62 samples. If such gastrointestinal virus could induce the protean symptoms of CFS, or only the local G-I symptoms, will take a lot more work. The authors quote their earlier work which suggested that antiviral therapy (ribavirin and alpha-interferon) may reduce the G-I symptoms, but much more work needs done on this subject.
The authors' participation in clinical trials focused on the use of interferon stimulants begun almost a decade ago, but the work has yet to be published. Not only is this disease chronic, but solid scientific work has appeared at the same chronic rate. What has always been difficult to tease out in CFS is whether there underlying immune defects predispose to chronic microbial infection or if there is a true, initial microbial trigger (the stealth hypothesis) that results in wide spread immunosuppression. Dr. Nancy Klimas at the VA Medical Center in Miami has summarized elegantly in a recent paper the scope of the immune defects uncovered in CFS. Hopefully, soon there will be specific pharmacologic manipulations that can reduce the symptoms in our DFS patients who continue to suffer from this devastating disease.
The etiology of chronic fatigue syndrome (CFS) remains conjectural. There are broad-based immune deficiencies in some patients with CFS.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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