(Dr. Klimas is Professor of Medicine, Psychology, Microbiology, and Immunology, and director of the Allergy and Immunology Clinic at Leonard M. Miller School of Medicine)
Sick and Tired
By Jeanne Antol Krull
In 1984 a woman suffering from severe fatigue, body aches, and difficulty concentrating walked into the office of clinical immunologist Nancy Klimas, MD, with a medical file several inches thick -- the result of visits to more than a dozen doctors. One piece of treatment advice she was given: "Change your hair color and get a manicure. You'll feel better." But the patient knew better, telling Klimas simply, "I think there''s something wrong with my immune system." Klimas sent the patient''s blood sample to colleague Mary Ann Fletcher, Ph.D., professor of medicine, microbiology/immunology, and psychology, and asked her to "look at this any way you know how." Fletcher's lab was already doing groundbreaking work on the role of the body's natural killer cells, which kill tumor cells or any pathogens in the blood. Mary Ann reports back, ''There is something very odd about her blood work. She has less natural killer cell function than we see in end-stage AIDS patients, and her immune activation markers are very high," Klimas recalls. "I called the patient and told her, ''I can't tell you what's wrong, but your labs are very abnormal.'' She burst into tears, she was so happy to hear something was wrong with her."
[CFS] is characterized by profound fatigue that is not improved by bed rest and may be worsened by physical or even mental activity. No matter what the name or how debilitating the symptoms, those who suffered from it -- mainly women -- were called everything from hypochondriacs to just plain crackpots.
Klimas said "After treating more than 2,000 chronic fatigue syndrome patients over more than 20 years, I''ve seen patients who were angry and frustrated at trying to convince their physicians and loved ones that this is a real illness. They experience a level of disability equal to that of patients with late-stage AIDS and patients undergoing chemotherapy"
"A recent prospective study found the one single predictor of who is going to stay sick after a viral infection is the severity of the initial viral infection," says Klimas.
When it comes to treating patients, Klimas says you don't have to be a chronic fatigue expert -- it comes down to basic clinical principles. Patients tend to have three main problems in addition to fatigue: sleep disruption, autonomic dysfunction (delayed drops in blood pressure after standing), and pain."In particular, the patient takes a big step forward the day you get their sleep better. Sleep is a huge part of helping patients feel better right from the beginning."
Even though discovery of a cause is still elusive after more than two decades of searching, scientists have zeroed in on several key areas: infectious agents such as viruses, problems with hormone regulation in the body's endocrine system, disturbances in the autonomic regulation of blood pressure and pulse, and immunologic dysfunction.
As director of AIDS research at the Miami Veterans Affairs Medical Center, Klimas was already working with an existing team of UM and VA researchers on HIV, and she tapped into their expertise for this new battle. "We were this big, diverse, multidisciplinary team in HIV, and I said, ''Why can't we do the same thing in chronic fatigue?'' "In looking at what generally happens to someone with this disease, it's easy to see how everything can go haywire. ... Whatever has stirred up your immune system in the first place can end up disturbing your sleep. When you don't sleep properly, never going into stage three and stage four sleep, your body doesn't release the nighttime hormones such as cortisol. A stress hormone, cortisol is a big part of why we quiet our immune system. It peaks in the morning when we wake up and resets the immune system for the day." When that doesn't happen, the immune system that was activated yesterday gets even more activated today and the next day, and it starts releasing far too many cytokines, which are molecules that can make you ache all over and disrupt stage four sleep. These molecules can also cause adverse effects in the brain, leading to cognitive and memory problems. "What you end up with is this vicious cycle of fairly subtle dysregulation between the body's hormone system, the autonomic nervous system, and the immune system," Klimassays.
"Initially it was quite difficult to get funding," remembers Fletcher. "This was seen as a hysterical condition that middle-aged women might come down with." Fletcher recently received a new National Institutes of Health (NIH) grant to study the role of specific peptides neuropeptide Y (NPY) and dipeptidyl-peptidase (CD26) in the development of chronic fatigue. These molecules are important in the regulation of many physiological and disease processes in the immune, nervous, and endocrine systems.