Reviewed by Gail Kansky

The American College of Physicians' annual conference had one session on chronic fatigue syndrome. Unfortunately, the session was slated for early (7 a.m.) morning on the last day of the conference. Anthony Komaroff, M.D., opened the session by saying, "I think...what you'll hear is that there is a lot of evidence that there is a biological process to the illness as well, as with a lot of illnesses, in some patients a psychiatric component."

 Dedra Buchwald, M.D., who was a graduate student under Dr. Komaroff and is now at the University of Washington, explained that "CFS is not normal fatigue" and was, indeed, "a very specific disorder" that overlaps with fibromyalgia and can mimic depression and other psychiatric disorders." She said, "There are two cardinal features that are not part of the CDC (Centers for Disease Control and Prevention) criteria" and listed them as an acute onset that usually had a viral beginning and the presence of allergies.

Dr. Buchwald said CFS, "when surveyed in the community, is almost as common in men as women" and had a slightly higher number of African Americans. The common symptoms of CFS that overlap with fibromyalgia were cognitive complaints (95%), sleep (90%), headaches (almost 60%), and acute onset (57%). Patients with these problems usually could carry both diagnosis. About 20 to 40% of FMS patients can meet the CFS criteria while 20-75% can meet the FMS criteria (depending on which-study you believe!). She noted CFS also overlaps with temporal mandibular disorder (TMJ) where many patients report past domestic violence or abuse. There is also an overlap with multiple chemical disorder (MCS) especially with sensitivities to exhaust, pollutants, and perfumes. Of the 600 PWCs she sees in the Seattle area, a "cure" is rare...maybe 2%, but 40-70% report moderate to substantial improvement.

     Jay Levy, M.D., a professor of medicine at the University of California in San Francisco and one of the world's leading retrovirologists and herpesvirologists, got involved in this area because "we were under the impression, and still are, that there may be one particular virus that may elicit this syndrome." Daniel Peterson, M.D., who was involved in the Lake Tahoe cluster outbreak, has opened a "fatigue clinic" at the university.[Note: It has since closed.]

     Dr. Levy noted that there are three separate groups seen: 25% regain normal activity, 75% are almost recovered, 25% are in-between. He has not found a DNA or RNA virus that could be considered causal so far. EBV (Epstein-Barr Virus) and HHV6 (human herpesvirus 6) are known to be reactivated. Latent antibodies are abnormally reactivated but they are not causal.

     Is there any infectious agent involved? Dr. Levy feels the immune system, when looked at with flow cytometry, shows there is. CFS shows lowered 11B suppressor cells and an activated CD8 phenotype with a higher HLDR. "The numbers of cells may not be abnormal, but when you look at CD8 , especially CD8 plus 38DR, there is an abnormality in severe patients," said Levy. He has seen none of this in contacts of patients and this "is never seen in depression." The decrease on NK ( natural killer cell) activity is also "seen in people with acute viral illnesses which is, essentially, an activated immune system." But healthy people will resolve this problem and return to good health in about ten days. 

     While there is a change in 11B, a suppressor cell of CD8 ( a cytotoxic T cell), there is an increase in CD 28 which is another cytotoxic cell. It's a T cell that is also activated. While the macrophages are normal, the natural killer cell activity is down, so the PWC has a reduced ability to respond to viruses. Recovered patients resolve this problem. 

     "How active are the CD8 cells,they proliferate more in controls," said Dr. Levy. If you activate white cells, you activate CD69...CD69 is a brand new antibody...that is programmed to respond to a stimulus. In CFS, a significant increase is seen." Sending a patient's blood overnight to be tested is no good," he explained. "This must be done in the first 6 to 8 hours."

     Dr. Levy is looking at the cytokines that Nancy Klimas, M.D. reported upon. He believes "a virus attacks, does its damage, and leaves." The way to a cure, he believes, "is to suppress the hyperactive immune system." 

     Dr. Komaroff then addressed the question,"Why isn't it just depression?" He said, "It's a fair and obvious impression...but there are real differences clinically..." and that the overlap of a psychiatric illness is just seen in a small subset of PWC's. Although some features may lead some to believe it's depression, "some of the clinical features do not fit with major depression." Conversely, the objective evidence seen in depression is not seen in CFS. He added that no patient has ever been cured with antidepressants even when they have concomitant depression and no evidence of depression has ever been established.

     Dr. Komaroff spoke of "overproduction of cortisol in the hypothalamus leading to the overproduction of ACTH by the pituitary, leading to basal hypercorticolism that is different from healthy controls, different from major depression..." He also noted "ten neuroendocrine markers that were different that those found in depression."

    Althouth the majority of patients with CFS meet a criteria for a psychiatric disorder, Dr. Komaroff said, " Why isn't it all just depression? Because it's not!" He noted that exercise exacerbates the fatigue instead of relieving it , the guilt of depression is absent in CFS, anehedonia is central to depression but not in CFS, and suicidal ideation is not common in CFS. The only controlled trial of Prozac showed no improvement in depresssion in CFS (Lancet, 1996). 

Other features that differentiate CFS and depression are as follows: 

  • Romberg and tandem gait abnormalities in and some serial 7's test often failed.
  • Central nervous system problems sometimes experienced
  • Small punctate areas of high signal seen in MRI scans in greater numbers
  • Encephalopathy features are the same in CFS and in AIDS
  • SPECT scans often see " a moth-eaten pattern"
  • Autonomic nerous dysfunction that can't be fully explianed by deconditioning.
"What do we think is going on?" asked Dr. Komaroff. "A....state of immune activation...and some kind of dysfunction of the central nervous system, " he answered. He cautioned the attending physicians that patients are hypersensitive to any CNS medication or alcohol and to treat with medication " way below typical doses." He gave little helpful advice, however, on ways to treat the disabling symptoms seen with the illness..

The National CFIDS Foundation * 103 Aletha Rd, Needham Ma 02492 * (781) 449-3535 Fax (781) 449-8606