13 Year Follow-Up of Children & Adolescents with CFS/ME

[Guest guest]

Thirteen-Year Follow-Up of Children and Adolescents With Chronic Fatigue

Syndrome.

By S. Bell (Pediatrics. May, 2001)

ABBREVIATIONS. CFS, chronic fatigue syndrome; SF-36, Medical Outcomes

Study Short Form Health Survey; CDC, Centers for Disease Control and

Prevention; VAS, visual analog scale.

Chronic fatigue syndrome (CFS) is an illness of unknown cause characterized

by unexplained, debilitating fatigue usually worsened by exertion and not

resolving with rest, occurring in both children and adults. In addition to

fatigue,

patients experience an associated symptom pattern that includes headache,

sore throat, lymph node tenderness, muscle pain and subjective weakness,

joint pain, sleep disturbance, cognitive dysfunction, and neurologic

symptoms,[1-6] Although diagnostic criteria are available for adults,[7]

criteria

specific for children have not been developed.

Hypotheses concerning the cause of CFS have ranged from persistent

infection with viral or other agents to a primary psychiatric disturbance.

However, no specific infectious agents have been consistently linked to the

illness, and many adolescents with CFS have no demonstrable emotional

illness. More recent studies point toward abnormalities in autonomic nervous

system function.[8-10] Issues concerning epidemiology, immunology, and the

role of infectious disease have been hampered by lack of a diagnostic marker

and reliance on subjective symptoms. Because current adult diagnostic

criteria are relatively recent, few studies of the natural history of CFS have

been conducted.

Between January 1984 and December 1987, 214 persons experienced an

illness suggestive of CFS in an isolated rural community in upstate New York.

Of these persons, 46 (21.5%) were under age 18 years at illness onset. Some

of these children were reported earlier in a study showing no correlation with

Epstein-Barr virus antibody levels[11] and in a case-control, risk factor

study.[12] Because this apparent illness cluster occurred before the

publication of present diagnostic criteria for CFS,[7] criteria for diagnosis of

these patients were developed.[13]

For the pediatrician, the difficulty is more acute because of lack of specific

diagnostic criteria. Yet the pediatrician is often faced with the clinical

management of children and adolescents with numerous, medically

unexplained, somatic symptoms and activity-limiting fatigue. The present

study seeks to address the prognosis of CFS in a defined group of children

and adolescents over a 13-year span.

Participants

Forty-six children and adolescents who became ill between January 1984

and December 1987 had been interviewed and examined by one of us

(D.S.B.), often within days or months of symptom onset, although the

diagnosis of CFS was not made until at least 6 months of persisting

symptoms. All participants had unexplained, activity-limiting fatigue and

numerous somatic complaints. This study was conducted in a rural private

practice setting, and verbal consent was obtained from participants.

METHODS

The records of participants were reviewed for symptom pattern and type of

illness onset an average of 13 years after illness onset by the diagnosing

clinician and compared with the present adult criteria for CFS.[7] A

questionnaire was mailed to all participants inquiring about present health

status. The questionnaire included the following:

1. Current health assessment with 4 answer options: " I have recovered

completely and feel entirely well, " " I have never recovered completely but feel

pretty well, " " I recovered somewhat but remain ill, " and " I am more ill than I

was 10 years ago. "

2. Subsequent medical and emotional diagnoses.

3. Subjective effect of the illness on social and educational life.

4. Amount of time out of school because of illness.

5. Subjective assessment of illness severity during worst month of illness.

6. Visual analog score (0 = none; 10 = very severe) indicating present severity

of 12 symptoms seen in CFS (fatigue, sore throat, lymph node tenderness,

eye pain and/or light sensitivity, abdominal discomfort, headache, depression,

muscle pain, memory and/or attention problems, sleep disturbance, dizziness

and/or lightheadedness, and joint pain).

7. Medical Outcomes Study Short Form Health Survey (SF-36). This 36-item

instrument is self-administered and is designed to assess functional status

and quality of life. The 8 subscales in the SF-36 are physical, emotional,

social, role functioning, body pain, mental health, vitality, and general

health.

Higher scores indicate better health and less discomfort. This instrument has

been documented to have high reliability and validity in numerous patient

populations[14,15] and has been used in the assessment of CFS.[16,17]

RESULTS

Of the 46 participants, 35 (76.1%) completed and returned questionnaires. Of

the remaining 11 participants, present location was unknown for 5, and the

questionnaires were not returned by the remaining 6. Telephone discussion

with these latter 6 participants suggested a similar overall pattern of response

to those participants returning questionnaire, but their data were not included

in study results.

Twenty-four participants were female (68.6%), 11 were male (31.4%). The

average age of illness onset was 12.1 years (male: 11.1 years; female: 12.8

years). All participants retrospectively met current Centers for Disease Control

and Prevention (CDC) diagnostic criteria for CFS defined as a new onset of

unexplained, activity-limiting fatigue, not relieved by rest, not caused by

excessive exertion, and lasting at least 6 months. All participants had at least

4 of the 8 symptoms of the CDC criteria (cognitive dysfunction, sore throat,

tender lymph nodes, muscle pain, multijoint pain, headaches, unrefreshing

sleep, and postexertional malaise).[7] Eight participants (22.9%) had an acute

flu-like onset with symptom pattern occurring suddenly within a 1-week

period. The remaining 27 participants (77.1%) had a gradual onset of

symptom pattern over weeks to months. The majority of participants were

adolescents, and only 8 (22.9%) were [is less than] 10 years old at illness

onset. No participant had illness onset below age 5 years. See Table 1 for

demographic data.

TABLE 1. Demographic Data of Children and Adolescents

With Unexplained Chronic Fatigue With Illness Onset

Between January 1984 and December 1987

Sex (n = 35)

Male, 11 (31.4%)

Female, 24 (68.6%)

Type of onset (n = 35)

Acute, 8 (22.9%; 2 male, 6 female)

Gradual, 27 (77.1%; 9 male, 18 female)

Age at illness onset (n = 35)

5-9 y 8 (22.9%)

10-14 y 16 (45.7%)

15-18 y 11 (31.4%)

Onset symptoms

Unexplained fatigue 35 (100%)

Recurrent sore throat 32 (91.4%)

Myalgia 32 (91.4%)

Headache 30 (85.7%)

Lymph node tenderness 29 (82.9%)

Cognitive difficulties 27 (77.1%)

Multijoint pain 26 (74.3%)

As part of the entry criteria, no participant was clinically believed to have a

primary psychiatric disorder, substance abuse, or eating disorder to account

for the symptom complex. In addition to fatigue, the symptoms documented at

illness onset included sore throat (91.4%), myalgia (91.4%), headache

(85.7%), lymph node tenderness (82.9%), memory and attention difficulties

(77.1%), and joint pain (74.3%). Post-exertional malaise and sleep

disturbance were not systematically inquired about at illness onset. There

was a high frequency of abdominal pain, photophobia, sensation of fever, and

flushing, symptoms not presently included in adult diagnostic criteria.

At follow-up, no participant reported an alternative or subsequent medical

diagnosis that could have retrospectively explained the symptom complex.

Fibromyalgia was listed but not included in this analysis because of its

overlap with CFS.[18] Other diagnoses listed included endometriosis (2),

depression (2), posttraumatic stress disorder (1), migraine (1), in situ cancer

of the cervix (1), and mitral valve prolapse (1). No psychiatric

hospitalizations

were recorded.

In terms of outcome, 13 (37.1%) reported, " recovered completely and feel

entirely well. " Fifteen participants (42.9%) listed, " I have never recovered

completely but feel pretty well. " Four participants (11.4%) listed, " I recovered

somewhat but remain ill, " and 3 participants (8.6%) listed, " I am more ill than

I

was 10 years ago. " Thus, an overall favorable outcome was reported by 80%

of participants an average of 13 years after illness onset (Table 2).

TABLE 2. Subjective Assessment of Health at Follow-Up

Chosen Assessment

" I have recovered completely and feel 13 (37.1%)

entirely well. "

" I have never recovered completely but 15 (42.9%)

feel pretty well. "

" I have recovered somewhat, but remain ill. " 4 (11.4%)

" I am more ill than I was 10 years ago. " 3 (8.6%)

Of the 13 participants " completely recovered, " only 9 could date the length of

time from illness onset to recovery. In these participants, none recovered

within 1 year, 2 between 1 and 2 years, 1 between 2 and 3 years, 3 between

3 and 4 years, and 3 recovered after 4 years of illness. The longest recovery

occurred 9 1/2 years after onset. There was no correlation between degree of

recovery and the age at illness onset, gender, type of onset, or family

clustering. An attempt was made to assess severity during the " worst month of

illness " by estimating average daily activity, and no correlation was found to

outcome.

The educational impact of the illness most closely correlated with illness

outcome. Fourteen participants (40%) missed " little or no school, " 8 (22.9%)

missed from 1 to 6 months, 3 (8.6%) missed 6 to 12 months, 2 (5.7%) missed

1 to 2 years of school, and 8 (22.9%) missed [is greater than] 2 years of

school. Of these latter 8 participants, none reported complete recovery, 3

were " never recovered completely but feel pretty well, " 3 were " recovered

somewhat but remain ill, " and 2 were " more ill. " Of 14 participants who missed

" little or no school, " 10 (71.4%) " recovered completely, " and the remaining 4

(28.6%) were " never recovered completely but feel pretty well. "

Correlation of illness outcome by questionnaire and SF-36 was good

because participants reporting better recovery had higher scores in all 8

domains. Symptom analysis did not show correlation between specific

symptoms most prominent at onset and symptoms most prominent at follow-

up with exception of photophobia (data not shown). However, it should be

noted that visual analog scales (VASs) for symptom severity were not used at

illness onset.

The VAS scores used in data analysis were the sum of 12 symptom-specific

scores graded from 0 (no symptom) to 10 (very severe symptom). In general

the VAS sums correlated to degree of recovery in those participants who had

" completely recovered, " and those who were " more ill than at onset, " with

average scores being 15.4 for the former group and 74.7 for the latter. The 2

middle groups displayed considerable overlap with scores for " never

recovered completely but feel pretty well " ranging from 17 to 87, and

" recovered somewhat but remain ill, " ranging from 45 to 93.

Twelve participants (34.3%) believed that their illness did not have an overall

social effect on their life, 10 of whom reported they had recovered completely.

Sixteen participants (45.7%) believed that their illness affected their life to

a

mild degree, 3 (8.6%) believed that there was a moderate social effect, and 4

(11.4%) believed that their illness had a severe effect on their life. In

general,

the social effect paralleled the perceived illness outcome.

DISCUSSION

In this study, 35 children and adolescents were diagnosed with unexplained

chronic fatigue between 1984 and 1987 and followed for an average of 13

years. The criteria used in diagnosing this group of patients was described

previously,[13] and all participants would retrospectively fit CDC criteria for

CFS. Clinically, none had prominent emotional or behavioral symptoms or

were believed to have a primary emotional disorder.

The existence of cluster outbreaks of CFS has been one of the central

questions in current research. Although the medical literature describes over

50 CFS-like outbreaks,[19] the publication of these reports before 1988 has

left uncertainty that these illnesses would have met current criteria for CFS.

The children described in this study were part of a larger group of 213

patients, adults and children, in an isolated rural area containing no cities of

[is greater than] 15 000 population, thus implying a cluster outbreak. As

described in this study, there have been no subsequent medical explanations

for the original symptom complex or the persisting illness present in 20% of

the sample. Moreover, the clinical similarity of patients meeting CFS criteria

diagnosed after 1988 leave the authors with the conclusion that the

participants of this study had, and some continue to have, CFS. Whether

symptom resolution or persistence would be the same in sporadic cases of

CFS, as opposed to cluster cases, was not addressed in this study.

The adult literature on prognosis of CFS has been contradictory because of

differing diagnostic criteria before 1988 and variations in the definition of

improvement. Because CFS has no objective markers to validate symptom

severity, subjective impressions are relied on to assess outcome and are

subject to both exaggeration and denial, dependent on the coping style of

participants. The pediatric literature concerning the natural history of

unexplained chronic fatigue has been even more scant.

In a recent article, Krilov et al[4] conducted a follow-up telephone survey of

the families of 42 children with chronic fatigue from 1 to 4 years after medical

evaluation. At follow-up, 43% considered their child " cured, " 52% considered

their child " improved, " and 5% considered their child unchanged. et

al[5] described 15 adolescents followed for 13 to 32 months with 4 well

(26.7%), 4 improved (26.7%), and 8 unchanged or worse (53.3%). Marshall et

al[6] followed 17 children and adolescents over 16 months with 76%

demonstrating improvement, although 38% had occasional symptoms. A

minority were " persistently and severely affected. " In a case--control study,

et al[3] compared 31 children with chronic fatigue to both healthy

children and those with depression. Half of the participants with chronic

fatigue were reevaluated at 17 months with 3 being cured and the remainder

improved.

In the present study, an overall good functional outcome was reported in 80%

of participants an average of 13 years after onset. Many of the participants of

this study have been followed by the same clinician for the entire length of

illness, and our observations are in keeping with those of Krilov et al[4] that

as

improvement occurs, periods of severe debility become shorter and less

frequent. However, we also notice that in those who do not improve, coping

skills develop so that moderate symptoms are modified by a lifestyle that

includes activity restriction, flexibility of daily schedule, and avoidance of

sustained activity.

The lifestyle variation is the most difficult factor to analyze in studies

attempting to address the natural history of unexplained chronic fatigue. We

compared perceived illness outcome (by questionnaire and SF-36) with

specific symptom severity (VAS scores). CFS is characterized by somatic

symptoms that may vary in severity but persist over time. Nine participants

reported complete resolution of illness and had VAS scores below 25 as

would be expected in complete recovery. Four participants reporting illness

resolution had VAS sums ranging from 28 to 48, indicating mild

symptomatology. Of those participants considering themselves " never

recovered completely but pretty well, " 2 had low VAS sums between 10 and

19, 6 had moderate VAS sums between 25 and 49, and 5 had high VAS sums

between 50 and 87. Two participants did not record VAS scores with 1

expressing health identity confusion by writing in the margin of the

questionnaire, " The survey is hard to answer because ... I was so young when

I became ill, I do not know if I am a well person, or a person who thinks he is

well but doesn't know what well really is. " Thus, perception of complete illness

resolution and low VAS scores suggesting minimal, if any, symptoms were

reported in only 25.7% of the entire group. This wide variation in somatic

discomfort has been the cause of the difficulty in assessing overall outcome in

CFS and needs additional clarification.

The best predictor of eventual outcome was the amount of school missed

during the first years of illness. All participants in this study were managed

during the early years of their illness by one clinician (D.S.B.) and all were

encouraged to attend school as much as possible, with home tutoring

provided when school attendance was not possible. Thus, differences in

clinical approach and management is unlikely responsible for clinical

outcome. Because increasing time missed from school correlated with a

poorer outcome, it can be argued that illness severity during the first years of

illness was a predictor of outcome. It can also be argued that school

absenteeism is a psychosocial marker reflecting illness behavior, but this

trend was not observed by the treating clinician. However, this possibility

needs to be more fully explored.

In the present study, no participant was diagnosed with another medical

illness that could have retrospectively explained the chronic fatigue. Thus,

unexplained chronic fatigue is unlikely to be a precursor to another medical

illness. Although this study was not designed to explore psychiatric illness, no

participant experienced psychiatric hospitalization or listed significant

psychiatric illness, substance abuse, or eating disorders as a diagnosis in the

years following illness onset.

It has been suggested that children with CFS not be given the diagnosis

because it would encourage illness behavior.[20] In our opinion, this would

have created severe difficulties in clinical management. The use of the

diagnostic term CFS, while not implying cause, was helpful in reducing both

patient anxiety and unnecessary laboratory evaluations and in attempting

symptom control. It has also been suggested that persistence of symptoms in

illnesses without clear cause is related to encouragement by " sympathetic

physicians. " [21] Ten participants in this study (28.6%) maintained contact and/

or were clinically managed for [is greater than] 10 years by the diagnosing

physician who would be considered sympathetic to the diagnosis of CFS,

whereas 25 participants (71.4%) were not followed clinically after the early

years of illness. Results from questionnaire showed no differences in clinical

outcome between these 2 groups, implying that clinician empathy was not a

prognostic factor.

This study has several limitations. Diagnostic criteria for unexplained chronic

fatigue were not available in 1984 and the criteria developed, although

similar to the present CDC criteria, were designed for this specific group of

patients. At present, diagnostic criteria for CFS have not been developed for

children, and developing specific pediatric criteria would be helpful for the

pediatrician. VASs were not obtained for the 12 symptoms at illness onset that

would have allowed a more accurate assessment of specific symptom

persistence. Finally, the natural history seen in this study sheds little light

on

the current controversies surrounding the role of emotions in unexplained

chronic fatigue, although it remains the clinical opinion of the authors that

emotions had little to do with either illness onset or illness persistence.

*Posted by Moderators