CFS in Adolescents -Follow-up Study

J.VAN.ROIJEN@CHELLO.NL (JAN VAN ROIJEN) 2004-03-03 17:05:40

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4 March 2004
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From: Fred Springfield
Via: CO-CURE@LISTSERV.NODAK.EDU

Chronic Fatigue Syndrome in Adolescents
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A Follow-up Study

Journal: Arch Pediatr Adolesc Med. 2004 Mar;158(3):225-9.

Authors: Gill AC, Dosen A, Ziegler JB.

Affiliations: Departments of General Pediatrics and Immunology,
Allergy, and Infectious Diseases, Sydney Children's Hospital,
Sydney, Australia.

NLM Citation: PMID: 14993080

OBJECTIVES:
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To compare the frequency of persistent symptoms up to 8 years
after illness onset in adolescents diagnosed as having chronic
fatigue syndrome, idiopathic chronic fatigue, and unexplained
fatigue for less than 6 months, and to determine if hospital
admission is associated with outcome.

DESIGN:
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A cohort study using questionnaire follow-up.

SETTING:
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A tertiary referral hospital.Patients Consecutive adolescents
referred for assessment of persistent fatigue were identified and
retrospectively divided into 3 groups according to the diagnostic
criteria for chronic fatigue syndrome and idiopathic chronic
fatigue.Intervention A questionnaire was designed and
administered by telephone at a mean of 4.57 years after the
initial examination.Main Outcome Measure The persistence of
self-reported symptoms was compared with respect to patient
group and admission.

RESULTS:
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Outcome data were obtained for 34 (69%) of the 49 eligible
subjects. Twenty-five percent of the chronic fatigue syndrome
group showed near to complete improvement, 31% showed
partial improvement, and 44% showed no improvement. The
idiopathic chronic fatigue group had near to complete recovery
in 50%, partial in 10%, and no improvement in 40%. Those with
unexplained fatigue for less than 6 months had all recovered.
There was no difference between the outcome of the subjects
admitted to the hospital and those managed as outpatients.

CONCLUSIONS:
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Adolescents with less than 6 months of fatigue have a good
outcome. Unexplained fatigue lasting more than 6 months has a
similar outcome regardless of the presence of minor criteria for
chronic fatigue syndrome.

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Editorial
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Functionally disabling chronic fatigue is a familiar complaint in
adult primary care settings, infrequent among adolescents, and
very rare in children. For more than a century, a syndrome of
chronic fatigue associated with various physical and cognitive
symptoms has been described with terms including
neurasthenia, Akureyri disease, Royal Free disease, myalgic
encephalomyelitis, postviral syndrome, and chronic fatigue
syndrome (CFS). Scant data estimate that pediatric CFS has a
prevalence ranging from 23 to 116 of 100 000 children and
adolescents with an approximate 2.5:1 female to male ratio.1
Various diagnostic criteria have been proposed, but most
researchers today use the 1994 Centers for Disease Control
and Prevention (Atlanta, Ga) revised CFS criteria2 that require
the presence of medically unexplained, profound, persistent or
intermittent fatigue associated with significant functional
disability for greater than 6 months and the presence of 4
additional symptoms (eg, headache, polyarthralgia, tender
adenopathy, impaired memory). Those with at least 6 months of
disabling fatigue but an insufficient number of symptoms to meet
the Centers for Disease Control and Prevention CFS criteria
have been labeled as having idiopathic chronic fatigue. While
excluding most major psychiatric disorders, the Centers for
Disease Control and Prevention criteria do allow some
comorbid psychiatric symptoms, including anxiety and
nonmelancholic depression, which may be problematic since
both anxiety and depression have a well-established,
independent relationship with fatigue.3

Because there are no specific signs, symptoms, or diagnostic
studies that define a case of CFS, this diagnosis has evoked
significant controversy among researchers and physicians. On
one end of the spectrum are those who are convinced that CFS
has a primary organic cause, such as a latent viral infection,
immunological dysfunction, endocrine imbalance, or autonomic
dysregulation. At the other extreme are those who view most of
the minor physiological perturbations that have been associated
with CFS as epiphenomena to a primary psychological process.
It is not established that all adolescents meeting CFS criteria
have the same condition, nor that adolescent and adult cases
represent the same disorder. It is also important to recognize
that most populations evaluated for proposed etiologic factors
are composed of adult patients with CFS. While frequently
indicating minor abnormalities, a review of the current CFS
literature provides no definitive evidence for a major etiologic
role of a specific infectious agent, immune dysfunction, disorder
of the hypothalamic-pituitary-adrenal axis, primary sleep
disorder, or neuromuscular dysfunction.4 Current evidence
suggests that adolescent CFS is not a homogenous disorder, a
single causative factor is unlikely to be found, and its etiology
involves multiple factors with variable expression in any
individual case.

Perhaps more commonly in adolescents than adults, a subset of
patients with CFS appears to have a disturbance of autonomic
nervous system control that is manifested as the postural
orthostatic tachycardia syndrome (a variant of orthostatic
hypotension); but whether this is causal, incidental, or secondary
to other factors, such as deconditioning, is still open to debate.5
Among adolescents who meet CFS criteria, more than one third
will have concurrent psychiatric diagnosespredominantly
depression and, less often, anxiety disorders.6-7 Several
studies have found that adolescent patients with CFS have more
internalizing symptoms, somatic complaints, or functional
disability than adolescents with chronic disorders such as
arthritis, cancer, or cystic fibrosis.8-10 Whether psychological
distress is primary in adolescent CFS or reactive to functional
disability imposed by fatigue and other symptoms is central to
the debate surrounding this puzzling disorder.

Adolescents with CFS and their parents, perhaps perceiving
disbelief in the eyes of their physicians, often seem guarded
regarding any possible psychological attribution of their
symptoms. Unfortunately, this may complicate obtaining an
appropriate psychosocial history and assessment for anxiety
and depression that are often comorbid with CFS. Additionally,
diagnostic uncertainty, coupled with parental concern, often
leads the primary care physician to order extensive laboratory
testing and subspecialty consultation that usually shed little
additional light on the diagnosis. What then constitutes an
appropriate primary care evaluation of the adolescent with
chronic fatigue? First, it is important to assess the degree of
disability. Healthy adolescents more often than not endorse the
symptom of fatigue when asked, but they do not miss school
because of it. Indeed, excessive school absenteeism is the
hallmark of adolescent CFS.11 Second, as indicated in the
report by Gill et al12 in this issue of the ARCHIVES, it is prudent
not to initiate an extensive workup in subacute cases because
those with less than 6 months of persistent fatigue very frequently
improve spontaneously.

The physical examination of adolescents with CFS is generally
unremarkable. Weight loss or growth delay suggests an
underlying organic disorder, depression, or an eating disorder.
Routine supine-to-standing blood pressure measurement is
unfortunately not a sensitive screen for postural orthostatic
tachycardia syndrome, and patients with symptoms such as
postural dizziness, nausea, or visual changes may warrant a
clinical diagnosis of orthostatic hypotension or referral for
tilt-table testing. A select laboratory evaluation including a
complete blood cell count, acute-phase reactant, thyroid screen,
routine chemistry panel, and urinalysis is indicated in all patients
to rule out occult presentations of organic conditions such as
hypothyroidism, inflammatory bowel disease, or renal failure.
Unless specifically suggested by history or examination, other
studies such as viral titers, immunological or endocrine tests,
and neuroimaging are rarely useful in establishing the diagnosis
of adolescent CFS. Because stress, anxiety, and depressive
disorders are common in CFS, a careful psychosocial
evaluation including separate confidential interviews with the
adolescents and their parents is imperative in all cases.

Cognitive behavior therapy and a graduated exercise program
are the only treatments that have been shown to be effective in
controlled studies of adult CFS.13 In the current study by Gill et
al,12 no significant difference in outcome was noted between
adolescents who were hospitalized briefly for physical therapy,
graduated exercise, and psychiatric evaluation compared with
those without this intervention.12 There are no published
controlled treatment trials of adolescent CFS, but the following
empirical management seems reasonable. Individual target
symptoms often are improved with specific therapy such as
nonsteroidal anti-inflammatory agents for headache and
musculoskeletal pain or selective serotonin reuptake inhibitors
for anxiety or depressive symptoms. Careful attention should be
given to sleep habits because many adolescents with CFS have
sleep latency, late awakening, unrefreshing sleep, prolonged
daytime naps, and the risk of developing sleep-phase
abnormalities. A balanced nutrition plan with adequate fluid
intake should be promoted. If orthostatic intolerance is
suspected, increased salt and water intake is an appropriate
initial step that may be augmented with mineralocorticoid and
peripheral-vasoconstrictor therapy as indicated. Prolonged bed
rest and physical inactivity should be discouraged because they
promote further deconditioning and persistence of CFS. A
gentle incremental exercise program with emphasis on strength,
flexibility, and graduated aerobic conditioning should be
instituted. Emphasis should be placed on maintaining normal
academic, social, and physical function as much as possible.
While school avoidance is unlikely to be the primary problem in
most cases, continued absenteeism further isolates the
adolescent and promotes identification with the sick role.

Although there are few longitudinal data and most of it comes
from patients referred to academic centers, it appears that the
prognosis for adolescents with CFS is better than that for adults.
While symptoms may persist for months or several years, most
adolescents with CFS have a satisfactory outcome with
approximately half reporting complete recovery; one third,
marked improvement; and the remainder, unchanged or
worse.7, 14-15 Gill et al12 noted similar results and additionally
found that 50% of adolescents with idiopathic chronic fatigue
were nearly or completely recovered compared with 25% of
those with CFS. Because an additional 31% of patients with
CFS and 10% of patients with idiopathic chronic fatigue
reported significant improvement although still symptomatic,
more than half of all chronically fatigued adolescents were
significantly improved at follow-up. Given this data, an optimistic
stance by the provider seems appropriate, and patients and
parents should be advised that the majority of adolescent
patients with CFS improve with time.

Mark Scott Smith, MD
Adolescent Medicine Section
Children's Hospital and Regional Medical Center
Mailstop 4H-1
Box 359300
Seattle, WA 98105

REFERENCES
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6. Smith MS, Mitchell J, Corey L, et al. Chronic fatigue in
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11. Smith MS, Martin-Herz SP, Womack WM, Marsigan JL.
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Accessed January 12, 2004.

12. Gill AC, Dosen A, Ziegler JB. Chronic fatigue syndrome in
adolescents: a follow-up study. Arch Pediatr Adolesc Med.
2004;158:225-229.

13. Whiting P, Bagnall A, Sowden AJ, et al. Interventions for the
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14. Krilov LR, Fisher MF, Friedman SB, et al. Course and
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15. Bell DS, Jordan K, Robinson M. Thirteen year follow-up of
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Pediatrics. 2001;107:994-998.

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