Editorial
Adolescent Chronic Fatigue Syndrome

Arch Pediatr Adolesc Med. 2004; 158:207-208.

Smith MS.

Adolescent Medicine Section, Children's Hospital and
Regional Medical Center, Mailstop 4H-1, Box 359300, Seattle, WA 98105,
USA.

NLM Citation: PMID: 14993075


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
diagnoses—predominantly 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



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