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.
EPIDEMIOLOGY
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 23/100,000.2 As 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
PATHOPHYSIOLOGY
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
CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS
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.
DIAGNOSTIC EVALUATION
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
