NIH Brings Scientists Together to Evaluate Research on CFIDS in Adolescents

Report by Vicki C. Walker

April 28, 1998 was an historic day in the political and scientific recognition of young people with chronic fatigue syndrome (CFS).

On this date, dozens of CFS researchers, CFS advocates and government employees met to hear scientists discuss current research on CFS in adolescents. The meeting, which lasted from 8:30 am until 4:00 pm, was defined by the acknowledgment (by people in the room, at least) that adolescents get CFS and that it is a very serious and complex problem.

Opening Remarks
Dr. George Curlin from the National Institutes of Health (NIH) outlined the meeting's ultimate goal: to generate scientific interest in the study of CFS in children and adolescents, and to significantly boost government funding of this type of research. The NIH was a cosponsor of the meeting, along with the U.S. Department of Health and Human Service's Chronic Fatigue Syndrome Coordinating Committee (CFSCC).

Dr. Anthony Komaroff of Harvard University served as the meeting's moderator, which meant that he introduced the various presenters and topics and kept the meeting on track. In his opening remarks, Dr. Komaroff said that in any illness it is essential to consider a child's social and family environment when evaluating symptoms. Because of young people's different experiences and activities, illness is perceived and described differently by the patient and his or her family, he said.

These comments were reinforced by Dr. Gary Marshall from the University of Louisville. Dr. Marshall reviewed the history of research into chronic fatigue syndrome and related illnesses (such as the Epstein-Barr virus). He said that there has been no firm evidence that any single agent causes CFS, although many have been investigated, and that fatigue is a very common problem in the U.S. among people of all ages.

Dr. Marshall also announced that he would be writing a report about the meeting and submitting it for publication in a major peer-reviewed medical journal. He hoped that this would give CFS in adolescents more attention and correct many common misinterpretations about the disease.

The Five "Ws" (and Two "Hs")
Epidemiology is the study of a medical problem's "Who, What, When, Where, Why, How and How Many." There has not been much research into these questions in young people with CFS (YPWCs), so no one claimed to have the final answers. Even so, the preliminary findings were pretty interesting.

Dr. William Reeves from the U.S. Centers for Disease Control and Prevention (CDC) discussed four CDC studies which have tried to answer the "how many" question. Three of the studies have been completed, and one is about half-way finished.

The three completed studies found that the prevalence of CFS in adolescents varies between three and 116 cases of CFS per 100,000 teens. The wide range between these estimates is a reflection of the way the studies were done, said Dr. Reeves, and all of them used the very restrictive definition of adult CFS, which possibly produced estimates that are too low.

The CDC is now in the middle of a study in Wichita, Kan., in which people were randomly selected to be called and asked if anyone in their household had symptoms from the current definition of adult CFS. So far, they have determined that CFS is clearly present in adolescents about half as often as it is in adults.

Dr. Karen Jordan, a DePaul University psychologist, manages a large NIH-funded CFS epidemiology project in Chicago. Part of the study focuses on CFS in children and adolescents.

This study was very carefully designed, said Dr. Jordan, to weed out people with underlying medical or psychological illnesses that may be causing their symptoms. Another unique aspect of this study is that the initial screening questions don't just ask about fatigue and medical symptoms, but also ask about problems with school, learning or memory. Because these questions better reflect the way CFS is experienced by young people, Dr. Jordan hopes that this study will more accurately estimate the number of young people with CFS.

Close to the Source
Although no YPWCs spoke at the workshop, the next segment focused on the next-best thing: their personal physicians.

Dr. David Bell was a physician in tiny Lyndonville, N.Y., in the early 1980s when 47 children and 167 adults got CFS. After 14 or 15 years, he sent surveys to each of the 47 children to find out what had happened to them; 35 of them returned the questionnaires.

At follow up, 13 (37.1%) reported their CFS had "completely resolved," 15 (42.9%) were "well, but not resolved," four (11.4%) Aremain ill," and three (8.6%) said they were still Avery ill." None of the 35 reported having other medical diagnoses which could explain their symptoms. Although several reported that they had been diagnosed with depression, none of them had been hospitalized as a result.

He also asked the patients about the severity of the 12 most common symptoms of CFS. Four of the 13 who reported their CFS "completely resolved" had a degree of symptoms which indicated that they weren't healthy, and two of the 15 who said they were "well" had symptoms in the range of moderate CFS. Additionally, only four of the "completely resolved" group said their health was "excellent" and only five of the "well" group said their health was Avery good." Dr. Bell attributed these conflicting reports to the confusion in health identity caused by getting seriously ill at a young age.

Dr. Bell also asked about the educational impact of CFS. Fourteen of the 35 missed little or no school, eight missed 1-6 months, three missed 6-12 months, two missed 12-24 months, and eight missed more than two years. The missed education had "little, if any" impact on 10 patients, mild impact on 13, moderate impact on eight, and severe impact on four. All of the 14 who didn't miss school were either recovered or well, while five of the eight who missed more than two years were still ill.

Dr. Mark Smith, a pediatrician from the University of Washington, talked about the YPWCs he treats at the NIH-funded CFS Center in Seattle. He echoed earlier comments when he said that he believes CFS rarely occurs before puberty.

Since his clinic is a well-known referral center, he primarily sees kids who have aggressively pursued medical care for their symptoms. In contrast to reports from other doctors, Dr. Smith finds that there is very little psychiatric distress in the families of his patients, and the proportion of CFS patients with dysfunctional families is very similar to what he sees in other groups, such as kids with migraine headache.

Most of his patients are girls. Their worst symptom is headache, followed by fatigue and other forms of pain. Dr. Smith asks about the number of school days a child has missed in the prior month, because he finds that students with CFS are often too sick to attend a full day of school. (Sixteen percent of his patients are home schooled for medical reasons.) He recommended that future epidemiology studies incorporate questions about missed school days into their initial screening questionnaires.

Dr. Hank Feder from the University of Connecticut is troubled by the tendency of doctors to give up on kids they can't help. His goal in treating YPWCs is to ease the fears they and their families have due to the sudden development of a very serious and troubling illness. It's essential to help the patients and their families learn to cope, even though he finds his patients are often resistant to seeking mental health treatment.

When he diagnoses a child with CFS, he tells the family that it is a common illness with an unknown cause and no diagnostic test. He is careful to explain that the patient is not crazy, but recommends that a mental health professional is consulted to promote positive coping skills and ease the stress associated with having a chronic illness. He also advises the student to attend school as much as possible and to do as much activity as possible C not to the point of overdoing and crashing, but enough to help the patient feel productive.

A few years after they first became sick, 32% of Dr. Feder's CFS patients reported that their illness had not improved; 19% reported some improvement (they regained 25-75% of their pre-illness activity level) and 49% said they had recovered. Most people say they can't explain why they recovered, it "just happened."

A key question that meeting participants were trying to resolve is: Is CFS the same in young people as it is in adults? According to Dr. Timothy Coy from the University of Washington, it appears to be pretty much the same. In his study of young people with CFS at the CFS center in Seattle, he found that their symptoms were essentially the same as those of adults, and that the CDC case definition was equally effective in identifying kids and adults with CFS.

Dr. Coy's associate Dr. Dedra Buchwald talked about people who take a long time to recover from mononucleosis. Six months after they got mono, 12% of people haven't recovered. Researchers tried to identify common factors about these patients to help them figure out why they didn't recover as expected. The only predictors were being female and having lymph node swelling (adenopathy) when they got mono. Things that were studied and found to be irrelevant were current or past psychiatric illness, psychosocial stress and laboratory findings during the acute mono phase.

So, What Does CFS Do?
Following lunch, four researchers discussed their efforts to discover the pathophysiology of CFS in young people. In other words, they want to find out what body systems are involved in and affected by CFS.

Dr. Richard Bruno, of Englewood Hospital in New Jersey, became interested in studying the neurological problems of young people with CFS when he realized how similar the symptoms of CFS were to those experienced by people who had polio many years previously.

He found that CFS patients reported the following cluster of symptoms: difficulty staying awake during the day, trouble concentrating, frequent headaches and sore lymph glands. When he compared patients with CFS with a control group, this pattern of symptoms discriminated between the two groups, but the EEG tests did not discriminate between the groups or correlate with the patients' fatigue levels.

Dr. Bruno also found that CFS patients have difficulty maintaining attention, but that their attention deficits are different from those experienced by people with psychological illnesses, such as depression.

Dr. Bryan Carter from the University of Louisville studied the psychosocial characteristics of young people with CFS. He found that they are not clinically depressed, but they have more anxiety than healthy children. Compared to depressed children, they have higher self esteem, are higher achievers in school and are less likely to think about suicide. Although YPWCs are limited in their activities and time with friends, they don't blame their friends or feel ostracized like depressed kids do.

However, Dr. Carter found that the YPWCs had more concerns about their symptoms and their health compared to kids with depression and other chronic illnesses, such as juvenile rheumatoid arthritis. He also reported that YPWCs tend to reject psychological explanations for their illness and/or recovery and said he felt that this may be due to the way the YPWCs have been treated by the medical community.

Dr. Peter Rowe from Johns Hopkins University is a member of the group which first reported that CFS seems to be associated with orthostatic intolerance (OI, the inability to maintain normal blood pressure or heart rate while standing). He briefly reviewed this research, saying that prolonged standing provokes symptoms in CFS patients, whether or not they test positive in the laboratory for neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS) or another form of OI. He also said that even for those who do test positive for OI, the standard treatment only helps a portion of persons with CFS.

In addition to his work on OI, Dr. Rowe has been studying two other conditions which seem to be associated with CFS: gastrointestinal problems and Ehlers-Danlos syndrome. Working with Dr. Kevin Kelly, he has found that many PWCs have a hypersensitivity to food proteins which is not picked up on allergy testing. Symptoms include disinterest in eating, abdominal pain, gastro-esophageal reflux, heartburn, mucous in the vomit, apthous ulcers, diarrhea, constipation, fever and asthma. Dr. Rowe has found that unless this underlying food hypersensitivity is treated, treatment for other conditions (such as OI) is ineffective.

Ehlers-Danlos syndrome is a relatively rare connective tissue disorder which seems to be more common than expected in PWCs, said Dr. Rowe. It is characterized by extreme hypermobility (stretchiness) in the skin, joints and other connective tissue, easy bruising and scarring, and fatigue. People with Ehlers-Danlos can do things like bending their wrists backward to touch their forearms or pulling the skin on their eyelids until it touches their foreheads. Dr. Rowe suspects that this elasticity in the tissues may cause the pooling of blood in the extremities associated with OI.

Dr. Rowe concluded his talk by saying that focusing on non-infectious and genetic risk factors for OI may improve understanding and treatment of CFS, tests for OI should be included in standard screening for CFS, and CFS may be a consequence of OI.

Dr. Jim Jones discussed his work with allergy testing in CFS patients. His research showed that the main difference between allergy and CFS patients was that the CFS patients have more psychiatric illness. He hypothesized that having allergy promotes "illness behavior" and results in chronic illness.

A New Definition?
The meeting concluded with a roundtable discussion of the day's reports and existing challenges. The discussion centered on the question: is there a need for a new CFS case definition for adolescents? Most felt that screening criteria that incorporates the unique activities and experiences of adolescents would be useful.

Dr. Bell and others suggested that, in addition to fatigue and symptom criteria, school attendance would be a useful screening tool, since CFS is characterized by fatigue which interferes with daily activities. Dr. Smith concurred, saying it's very unusual to see a non-CFS child with fatigue so disabling that it keeps him or her from attending school.

No one was able to answer with certainty whether young children get CFS. It seemed to be quite unusual to find a pre-pubescent child with CFS, but the group hypothesized that this could be because CFS has not been studied in younger kids. Dr. Reeves suggested that a strong research effort on adolescents with CFS might improve the understanding of CFS in children, just as the research on adults eventually illuminated the problem in adolescents.