Rudolph's Pediatrics, 22nd Ed.

CHAPTER 208. Chronic Fatigue Syndrome

David S. Leslie

Generalized fatigue is a frequent complaint during many common pediatric infectious illnesses. Additionally, chronic diseases of childhood often are characterized by associated fatigue. The symptoms experienced by children with these conditions typically resolve with treatment of the acute illness or of the underlying chronic disease. In contrast, chronic fatigue syndrome (CFS) is distinguished by prolonged fatigue and associated constitutional symptoms that persist after improvement in the triggering disorder. CFS may be a debilitating illness that significantly impacts activities of daily living and family dynamics. A systematic approach directed at first ruling out identifiable causes of profound fatigue and associated symptoms is essential before arriving at the diagnosis of CFS. Through a careful history and physical exam, and narrowly focused laboratory testing based on clinical presentation, underlying diseases responsible for fatigue may be eliminated. Attention then switches to maximizing the ability to function and initiating an appropriate treatment plan. Although the specific cause of this illness remains to be elucidated and appropriate treatment strategies continue to be controversial, a multidisciplinary, holistic, symptom-based approach can provide the best tools for managing CFS and achieving full recovery.


The symptoms of chronic fatigue syndrome-like illnesses had been described in adults for many years, even prior to the acceptance of specific diagnostic and research criteria.1 However, the recognition that this illness affects children is a relatively recent phenomenon. Bell and colleagues initially described a cluster of pediatric patients who presented during the late 1980s with symptoms consistent with chronic fatigue syndrome and further defined the incidence in a rural community through a retrospective review.2 Over the past several years, several published reports have demonstrated that prolonged fatigue states and chronic fatigue syndrome do indeed occur in the pediatric population, and in fact they may not be rare. Although the etiology of chronic fatigue syndrome remains unknown, reports of clusters of cases imply that environmental triggers, such as infection, may play a role.

Children of all ages may present with chronic fatigue syndrome but evidence suggests that it is more common in the adolescent population than in younger children. The incidence and prevalence of chronic fatigue syndrome in children are somewhat difficult to assess given the absence of specific pediatric criteria, geographical variations, and other variables. Nonetheless, the few available data are fairly consistent: A study in Australian children reported an overall prevalence of 37 per 100,000,3 whereas the retrospective study done by Bell in the United States reported an estimated prevalence of 23/100,000.2As is the case in adults, pediatric chronic fatigue syndrome seems to be more common in girls, with an overall female to male ratio of 2:1, although some studies have failed to demonstrate such a female predominance.2 In addition, children in higher socioeconomic groups appear be affected more frequently.4


As in adults, the specific mechanisms through which children develop chronic fatigue syndrome remain unknown. Many theories have been proposed regarding the etiology of chronic fatigue syndrome. These have included immune dysfunction,5,6 dysregulation of the hypophy-seal-pituitary axis,7 chronic infection and alterations in the autonomic nervous system9 or in the metabolic response to stress. However, to date, there is no convincing evidence for a single genetic or environmental cause. Most specialists agree that the manifestations of chronic fatigue syndrome are likely multifactorial, with both physiological and psychological factors playing a role in development of the condition. Similarly, specific genetic influences on the development of chronic fatigue syndrome remain unknown, though the observation that chronic fatigue syndrome and related disorders appear to be more common within certain families suggests a possible heritable factor. The development of more sophisticated methods of genetic analysis may provide insight into the influence of inheritance on chronic fatigue syndrome.10


As long as specific pediatric criteria for chronic fatigue syndrome have not been established, the adult diagnostic criteria established by the Centers for Disease Control and Prevention (CDC) in 1988 and modified in 1994 must serve as a framework upon which to establish a likely diagnosis in children.1 Per current revised CDC criteria, following a careful exclusion of identifiable causes, diagnosis may be made if the patient meets both of the following criteria:

1. Clinically evaluated, unexplained persistent or relapsing chronic fatigue that is of new or definite onset, is not the result of ongoing exertion, is not substantially relieved by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities.

2. The concurrent occurrence of four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multijoint pain without swelling or redness; headaches of a new pattern, type, or severity; unrefreshing sleep; postexertional malaise lasting more than 24 hours.

These clinical criteria for identifying patients with possible chronic fatigue syndrome represent common pediatric symptoms that may be seen in a broad swath of childhood illnesses. For example, sore throat and tender lymph nodes may be present during acute viral infection or in the setting of streptococcal pharyngitis. Myalgias and arthralgias may be suggestive of acute infection, primary muscle disease, benign hypermobility syndrome, or chronic inflammatory diseases. Headaches and alteration in memory may occur secondary to infections, inflammatory diseases, mass lesions, or new-onset headache disorder. Additionally, the primary symptom of prolonged fatigue may be present secondary to altered sleep as a result of obstructive sleep apnea, or due to chronic diseases including anemia, rheumatologic conditions, malignancy, chronic infection, and hypothyroidism. Given these considerations, the potential differential diagnosis for a child presenting with fatigue and associated constitutional symptoms is broad. In addition to carefully reviewing the medical condition of children with suspected chronic fatigue syndrome, a thoughtful psychosocial assessment is essential for ruling out psychiatric illness, social factors such as disruption of family dynamics, or other stressors that may present with somatic symptoms.


Because many pediatric diseases can manifest with symptoms similar to those of chronic fatigue syndrome (CFS), this illness remains a diagnosis of exclusion. The first step in evaluating a pediatric patient for possible CFS is to obtain a detailed history (both medical and psychosocial) directed at diagnosing recognizable diseases that require a specific treatment plan. Additionally, performing laboratory studies in order to evaluate basic parameters, as well as focused laboratory testing based on information gathered via history and physical exam, is prudent. The Centers for Disease Control and Prevention (CDC) has recommended that adults undergoing consideration for possible CFS have basic laboratory testing as summarized in Table 208-1. These tests should also be considered in children presenting with possible CFS. Further laboratory testing, imaging, or other studies should be conducted in a focused manner based upon the history and physical exam. Although the currently accepted CDC diagnostic criteria for adults require fatigue greater than 6 months for the diagnosis of CFS, the pediatric literature suggests that this diagnosis may be more appropriately made earlier in children. A general algorithm for assessment of children with possible CFS is presented in Figure 208-1.

Table 208-1. Basic Screening Laboratory Studies to Assess for Underlying Disease

Alanine aminotransferase (ALT)


Alkaline phosphatase

Complete blood count

Blood urea nitrogen (BUN)


Electrolytes, glucose




Total protein

Other tests as indicated by clinical presentation

Data from Fukuda K, Straus SE, Hickie I, et al. Ann Intern Med. 1994;121:953-959.


The treatment of children with chronic fatigue syndrome should be directed toward relief of the specific primary symptoms manifested by the individual patient. Therapy should be multidisciplinary, focused on maintaining ability to function in activities such as school, sports, and social interactions. Medical therapy primarily consists of appropriate analgesics such as acetaminophen or nonsteroidal anti-inflammatory medications to treat musculoskeletal pain or symptoms such as headache. Evidence suggests that some patients with CFS also are affected by the postural orthostatic tachycardia syndrome (POTS).11 Patients with primary symptoms such as lightheadedness or dizziness with change in body position may feel better with medications such as fludrocortisone, alpha-agonists, or beta-blockers, and these are often helpful in children with POTS-like symptoms complicating chronic fatigue syndrome, too.

A significant percentage of children with significant prolonged fatigue may experience comorbid depression, anxiety, or other psychiatric illnesses, either as a preexisting condition or as a reaction to illness. Antidepressants, anxiolytics, or other psychotropic medications, may be indicated in these individuals at least in the short term to potentiate other interventions. Additionally, among the complex components of chronic fatigue syndrome, there is often a significant psychosocial contribution. Not surprisingly, therefore, cognitive behavioral therapy (CBT) typically has a salubrious effect. In a study of adults, CBT was more effective in restoring psychological well-being and exercise tolerance than either a conventional medical therapy or a program of education and support.12 Studies in adolescents with chronic fatigue syndrome have also suggested that CBT is an important component of treatment promoting improved ability to function and long-term outcome.13

FIGURE 208-1. Algorithm for the evaluation and treatment of suspected Chronic Fatigue Syndrome.

The specific recommendations for physical exercise in children with chronic fatigue syndrome (CFS) remain controversial. Additionally, studies in adults have been somewhat conflicting in determining whether aerobic capacity is impaired in patients with CFS.14 Nonetheless, a program of graded aerobic exercise consisting of a 1:3 ratio of exercise time to rest is currently recommended by the CDC. Overly vigorous exercise may lead to increased post-exertional malaise with recurrent cycles of relapse (the so-called over training syndrome). This presents a particular problem in the management of the child and adolescent with CFS, because it is often difficult for children to self-regulate their activities. Conversely, children with CFS often feel worse in the short term after exercising, so in order to avoid either excessive or inadequate exertion, careful oversight of exercise programs is important. Regular aerobic exercise may also help children adjust the disrupted sleep patterns that typify CFS. Therapeutic goals should include restoring normal sleep–wake cycles through appropriate sleep hygiene characterized by consistent bedtime and elimination of napping.

Because symptoms of chronic fatigue syndrome may persist for prolonged periods of time, it is essential to also focus on maintaining the ability of the child to function, particularly in the school environment. The practitioner should advocate for appropriate educational accommodations while promoting the affected child’s school attendance. An individualized educational plan often facilitates active school participation, augmented by supportive services such as tutoring as needed. In a study by Lim et al, adolescents with chronic fatigue syndrome were treated using a 4-week in-patient program incorporating gradual reintroduction of physical activity, psychological therapy, and reintroduction into the school environment. Although 66% of patients were not attending school prior to the program, 78% were able to attend school full time at long-term followup. No control group was reported, but these data still support the idea that multidisciplinary treatment may be effective in promoting the ability of individuals to cope with symptoms of chronic fatigue syndrome.15


The prognosis for children and adolescents with chronic fatigue syndrome appears to be more favorable than that of adults. Krilov et al. reported that on long-term follow-up, approximately 95% of patients were somewhat improved, whereas 43% noted complete resolution of symptoms.16 Additionally, in a 13-year follow up of the patient population originally described by Bell et al., approximately 80% of patients reported improvement with 37% reporting that the illness had completely resolved.17 This is not to say that the condition may be taken lightly, or that good outcomes may be assumed without expert management. As with many pediatric conditions, however, the combination of early aggressive therapy with a child’s natural resilience does allow caregivers to be optimistic when explaining expectations for children with chronic fatigue syndrome.