The baffling case of chronic fatigue.

The baffling case of chronic fatigue

The cause of chronic fatigue syndrome has eluded scientists. Past research suggested a link to the Epstein-Barr virus (EBV), but a number of scientists now question that connection. A report in the Dec. 29 NEW ENGLAND JOURNAL OF MEDICINE casts more doubt on the Epstein-Barr theory.

"Our findings suggest that active EBV infection is not a primary cause of [chronic fatigue syndrome] symptoms," says Stephen E. Straus of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "However, EBV as well as other viruses may still act to trigger the illness," he adds, referring to the theory that chronic fatigue may represent an abnormal response to an infection. Scientists think some patients never completely recover from a flu-like illness, but instead develop long-standing symptoms of chronic fatigue. The disorder has been dubbed the "Yuppie plague" because it is often diagnosed in professional women in their 20s and 30s.

Straus and a multicenter group of colleagues studied 24 patients with persisting EBV antibodies who had suffered debilitating fatigue for an average of 6.8 years. Half the study participants got acyclovir, a drug known to halt EBV replication. The other half received a placebo. Patients got intravenous injections of the drug or of a placebo every 8 hours for seven days; then they received oral administration for another 30 days.

The research team found virtually no difference between the placebo and the treatment group: At the end of the study, 11 acyclovir patients reported they felt better, but so did 10 placebo patients. "We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either a spontaneous remission of the syndrome or a placebo effect," the researchers say.

Acyclovir's failure has renewed researchers' skepticism regarding the role of EBV. "The results of this study add further weight to the doubts that have been expressed about active replication of the Epstein-Barr virus as the basis of the chronic fatigue syndrome," writes Morton N. Swartz of the Massachusetts General Hospital in an editorial accompanying the report. Robert T. Schooley at the Harvard Medical School in Boston echoes that sentiment. "The symptoms may be due to a variety of things," Schooley said in an interview. "It's unlikely that one thing is causing this disease."

Yet some researchers remain bullish on EBV's role in chronic fatigue. "The comment in the paper that EBV can't be causing this [syndrome] is really premature," says James Jones of the National Jewish Center for Immunology and Respiratory Medicine in Denver. Researchers need to learn more about acyclovir and its effect on EBV, he says. Jones notes that acyclovir also fails to help patients with infectious mononucleosis, a disease frequently caused by EBV.

But the new study adds to the mounting evidence against EBV. A March 1988 report by a Centers for Disease Control (CDC) working group found the link between EBV and chronic fatigue to be less than solid (SN: 3/12/88, p.167). That group rejected the name "chronic Epstein-Barr syndrome," noting that most people in the United States have EBV antibodies but show no evidence of disease. The CDC group renamed the disorder chronic fatigue syndrome and outlined strict criteria for its diagnosis. To meet the CDC's definition, a patient must have debilitating tiredness for more than six months and must exhibit at least eight of 11 symptoms, including sore throat, mild fever and muscular aches.

Straus and other researchers see a possible link between mood and chronic fatigue syndrome. "I don't know how big the psychological component is," Straus says. "It is possible that the physical features of chronic fatigue are intimately linked to brain chemistry and mood."