Fatigue and the Chronic Fatigue Syndrome

Peter C. Rowe

Fatigue is a private, subjective experience that, unlike muscle weakness, is difficult to quantify. It usually refers to an unpleasant, overwhelming sense of exhaustion that affects mental and physical activity, and differs from sleepiness or lack of motivation.¹ Acute fatigue is a common symptom in adolescents and young adults (AYAs); 20% to 35% report fatigue of at least moderate severity over the preceding month. Acute fatigue usually is readily explained by factors such as inadequate sleep, excessive work or physical training demands, psychosocial factors, iron deficiency, or self-limited medical conditions. Because it can be the initial sign of a life-threatening underlying medical or psychiatric condition—ranging from vasculitis to severe depression—or associated with more protracted and potentially disabling medical conditions such as chronic fatigue syndrome (CFS), the challenge is to differentiate the benign and self-limited from the disabling or dangerous conditions.

CAUSES OF FATIGUE

Fatigue can be associated with virtually any disease of any organ system.² Most causes of acute fatigue are readily apparent from the history, physical examination, and simple laboratory studies. Common causes include recent inadequate sleep or poor sleep hygiene, psychological distress, and infection.

Sleep requirements remain constant or increase through adolescence, averaging 9 hours per night, but many biologic, social, and scholastic pressures result in lower average amounts of sleep, closer to 7 hours nightly on weeknights.³,⁴ In addition, most AYAs sleep more on weekends than they do during the week. Sleep disorders are increasingly being recognized as a cause of fatigue and/or daytime sleepiness in AYAs (see Chapter 25). These include the following:

Insomnia is defined as decreased sleep quality and/or quantity due to trouble falling asleep and/or maintaining sleep. Insomnia may be a symptom of an underlying medical or psychological disorder, part of a delayed sleep phase syndrome (DSPS), or unexplained. DSPS is a common disorder “in which an individual’s internal circadian pacemaker is not in synchrony with internal or environmental time.”⁵
Obstructive sleep apnea occurs in up to 1% to 3% of adolescents and may be caused by enlarged tonsils and adenoids, obesity, retrognathia, or nasal obstruction.
Other sleep disorders are uncommon; they include narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, periodic leg movements during sleep, and restless leg syndrome.

Psychological disorders that can be associated with too little sleep and increased fatigue include depression, anxiety, stressful situations, or bipolar disorder. Generally, a thorough history from the patient and parent will illuminate symptoms of a mental health disorder that correspond to the onset of excessive fatigue.

Fatigue can also result from medications including antihistamines, sedatives, antidepressants, and other psychotropic medications, alcohol, or illicit drugs. In addition, infectious diseases such as mononucleosis, hepatitis, chronic infectious diseases such as HIV, tuberculosis, or Lyme disease, or bacterial endocarditis may also result in daytime sleepiness. Finally, endocrine disorders including thyroid disease, adrenal disease, or diabetes mellitus as well as other systemic illnesses (e.g., connective tissues diseases, anemia, neoplasms, congenital heart disease, asthma, inflammatory bowel disease, or kidney or liver failure) will also produce fatigue.

Red flags for more serious conditions include unexpected weight loss, fevers, abnormalities on the neurologic examination, generalized lymphadenopathy, adventitious sounds on the lung examination in someone without asthma, fatigue during exertion, clubbing, bronzing of the skin, and erythematous, swollen joints.

CHRONIC FATIGUE SYNDROME

CFS is a relatively common disorder affecting AYAs. It has a heterogeneous group of precipitating and perpetuating factors, and is characterized not only by fatigue but also by an inability to engage in cognitive and physical exertion without a marked exacerbation of symptoms. To maximize functioning of affected individuals, symptomatic treatment should begin before 6 months of fatigue have elapsed and prior to diagnostic confirmation of CFS.

Epidemiology

Population-based studies have shown that CFS affects previously healthy, active individuals from all socioeconomic strata and from all races.⁷ Prevalence estimate varies depending on the CFS definition, but has been estimated at 1 to 3 per 1000 in AYAs.⁸ While CFS is much more common after age 10, when present in younger children, the symptoms are similar to those who are older.⁹ Females are more likely to develop CFS than males, in a ratio of 2-4:1. Across the globe, CFS is a common reason for home tutoring and prolonged inability
to attend regular school classes. The factor that most closely predicts school attendance is physical functioning as opposed to mental health and/or behavioral issues.¹⁰

TABLE 35.1 International Consensus Committee Criteria for Chronic Fatigue Syndrome^a

Fatigue criteria

The fatigue must be clinically evaluated, otherwise unexplained after evaluation, persistent or relapsing for more than 6 months, of new or definite onset (not lifelong), not the result of ongoing exertion, not substantially alleviated by rest, associated with a substantial reduction in previous levels of occupational, educational, social, or personal activities.

Symptom criteria

The fatigue must be accompanied by concurrent occurrence of four or more of the eight symptom criteria, all of which must have persisted or recurred during the 6 or more months of the illness:

Self-reported impairment in short-term memory or concentration
Sore throat
Tender cervical or axillary lymph glands
Unrefreshing sleep
Muscle pain
Multi-joint pain without joint swelling or redness
Headaches of a new type, pattern, or severity
Postexertional malaise lasting more than 24 hours

^aExclusionary criteria and conditions that can be comorbid with CFS, and ambiguities in the 1994 definition can be found in Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994;121:953-959.; Reeves WC, Lloyd A, Vernon S, et al. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res 2003;3:25.

Etiology

Infection

The onset of CFS can be abrupt—associated with a flu-like or mono-like infection—but gradual onset of symptoms is also common.¹¹ However, no single pathogen has been identified as a cause for all CFS. Finally, evidence of persistent infection has not been detected in those with CFS.

While fatigue affects virtually all patients at the onset of infectious mononucleosis, only 13% of these patients meet CFS criteria after a 6-month duration of this symptom.¹²
After certain other acute infections, up to 10% of AYA patients can develop CFS; the severity of the initial infection appears to be a main risk factor, not the patient’s premorbid behavioral state.¹³
Immune abnormalities are variable, and autoimmune phenomena are occasionally present; there are no clear features consistent with a classical immunodeficiency disorder.¹⁴

Mental Health

Depressive and anxiety disorders must be evaluated carefully to disentangle the presence of these disorders and CFS. Depression shares some clinical features with CFS, including fatigue, nonrestorative sleep, and difficulty concentrating. However, AYAs with depression are distinguished from those with CFS by the dominance of low mood and loss of pleasure in activities.

For those AYAs with CFS, adjusting to a chronic, debilitating illness can sometimes lead to depression. As many as half of CFS patients develop depression at some time during the course of their illness. Such patients need to be assessed for the severity of depression and evaluated for treatment. Providers need to be aware that various classes of antidepressant drugs may worsen CFS symptoms. In addition, depression or other psychological disorder may warrant referral to a mental health profession.

TABLE 35.2 Prevalence of Fukuda Symptoms in AYAs with CFS

Symptom	Prevalence (Range) (%)
Unfreshing sleep	84-96
Postexertional malaise	80-96
Memory/concentration problems	79-84
Headaches	75-78
Muscle pain	59-73
Joint pain	48-67
Sore throat	43-57
Tender nodes	31-44

TABLE 35.3 Other Symptoms Reported with Moderate Severity in AYAs with CFS

Symptom	Prevalence (Range) (%)
Lightheadedness	70-100
Abdominal pain	50-70
Nausea	40-55
Temperature fluctuations	50
Heart racing	40-45
Shortness of breath	35-40
Chest pain	35-40