eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Chronic Fatigue Syndrome

Author: Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Coauthor(s): Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College; Bryan D Carter, PhD, Professor of Child Psychology in Psychiatry and Behavioral Sciences, Chief Psychologist in Division of Child and Adolescent Psychiatry, Director of Predoctoral Internship in Clinical Child/Pediatric Psychology, Director of Postdoctoral Fellowship Program in Pediatric Psychology, Director of Pediatric Consultation-Liaison Service to Kosair Children's Hospital, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Jan 21, 2009

Introduction

Fatigue is one of the most common symptoms in clinical medicine; nevertheless, fatigue may be difficult to define because it is rather loosely partitioned into physical and mental components. Fatigue often proves evanescent or, if chronic, relates to an underlying systemic illness. Fatigue may also be associated with a psychiatric disorder. Less commonly, patients may have chronic persistent fatigue that lasts longer than 6 months without an apparent etiology and that is associated with exercise intolerance, sleep difficulties, and an inability to perform mental or physical activities in a competent fashion.

Because a healthy body requires robust, functionally integrated organ systems to ensure optimal operation, intact organ parenchyma, intact organ regulatory systems, and intact delivery of nutrients and oxygen to the tissues by the cardiovascular-circulatory system must be present to avoid malfunction. Any defect in these 3 components causes organ dysfunction. Signals sent via the nervous system indicating such dysfunction may be perceived as pain or fatigue. If dysfunction progresses to critical organ impairment, the organ system may ultimately fail; however, more gradual and persistent decline in function of single or multiple organ systems can produce a chronic fatigue state without complete organ system breakdown.

The etiology of organ fatigue remains elusive, and, indeed, the precise definition of fatigue remains controversial. Nevertheless, standardized questionnaires and examinations are currently used to assess fatigue and to separate mental fatigue from physical fatigue on the basis of general physical condition and on the ability to perform cognitive or muscle tasks in an age-appropriate fashion.

For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center, Muscle Disorders Center, and Back, Ribs, Neck, and Head Center. Also, see eMedicine's patient education articles Chronic Fatigue Syndrome, Fibromyalgia, and Fatigue.

Chronic Fatigue Syndrome Defined

As a distinct clinical entity, chronic fatigue syndrome (CFS) has only recently been defined for adults as a distinct disorder characterized by chronic (often relapsing but always debilitating) fatigue lasting at least 6 months (occasionally lasting much greater lengths of time), which causes impaired overall physical and mental functioning. The US Centers for Disease Control and Prevention (CDC) criteria have been broadly formulated in order to standardize research in the field, resulting in an operating framework that includes cognitive difficulties, pharyngitis, tender lymphadenopathy, muscle pain, joint pain, headache, sleep disturbance, poor sleep, and postexercise malaise.

Because a precise etiology for the syndrome remains elusive, the diagnosis is largely made once specific medical and psychiatric disorders are excluded. Therefore, stating that CFS is an illness primarily characterized in adults by self-reported symptoms with a relative paucity of physical findings may be fair.

The most recent CDC diagnostic criteria state:1

In order to receive a diagnosis of chronic fatigue syndrome, a patient must satisfy two criteria: 1) Have severe chronic fatigue of six months or longer duration with other known medical conditions excluded by clinical diagnosis; and 2) concurrently have four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern or severity; unrefreshing sleep; and post-exertional malaise lasting more than 24 hours. The symptoms must have persisted or recurred during six or more consecutive months of illness and must not have predated the fatigue.

In addition, a large number of clinically defined, frequently treatable illnesses can result in fatigue. Diagnosis of any of these conditions excludes a definition of CFS unless the condition has been treated sufficiently and no longer explains the fatigue and other symptoms. These conditions include hypothyroidism, sleep apnea and narcolepsy, major depressive disorders, chronic mononucleosis, bipolar affective disorder, schizophrenia, eating disorders, cancer, autoimmune disease, hormonal disorders, subacute infections, severe obesity, alcohol or substance abuse, and reactions to prescribed medications.

The revised CDC case definition (abridged version) states:

Any unexplained abnormality detected on examination or other testing that strongly suggests an exclusionary condition must be resolved before attempting further classification. Conditions that do not exclude a diagnosis of CFS include:

1. Any condition defined primarily by symptoms that cannot be confirmed by diagnostic laboratory tests, including fibromyalgia, anxiety disorders, somatoform disorders, nonpsychotic or melancholic depression, neurasthenia, and multiple chemical sensitivity disorder.

2. Any condition under specific treatment sufficient to alleviate all symptoms related to that condition and for which the adequacy of treatment has been documented, including hypothyroidism for which the adequacy of replacement hormone has been verified by normal thyroid-stimulating hormone levels, or asthma in which the adequacy of treatment has been determined by pulmonary function and other testing.

3. Any condition, such as Lyme disease or syphilis, that was treated with definitive therapy before development of chronic symptoms.

4. Any isolated and unexplained physical examination finding, or laboratory or imaging test abnormality that is insufficient to strongly suggest the existence of an exclusionary condition, including an elevated antinuclear antibody titer that is inadequate, without additional laboratory or clinical evidence, to strongly support a diagnosis of a discrete connective tissue disorder.

Laboratory tests can neither confirm nor definitely exclude CFS, although the CDC recommends a "basic battery" that usually includes a CBC count, liver function tests, thyroid function tests, erythrocyte sedimentation rate, and serum electrolyte level measurement. The authors also usually include an antinuclear antibody and morning cortisol measurements.

Historic Aspects of Chronic Fatigue Syndrome

Although only recently codified by CDC case definition, chronic fatigue syndrome (CFS) has had its homologues for many years, including such poorly described disease states as neurasthenia, Da Costa syndrome (reported after the American Civil War), chronic mononucleosis, and vapors. Straus nicely summarizes these homologues in his historic monograph.2 More current terms, such as myalgic encephalitis (a British designation), presume an origin for an illness with no established pathogenesis; however, a common thread embedded within this nomenclature includes an underlying stressor, which is often an inflammatory antecedent.

Also, diverse nomenclature provides clues to the etiology. In this sense, the illness is similar to posttraumatic stress disorder and the recently reported Gulf War syndrome; however, no causative relation between infection and the syndrome has been definitely established, despite strenuous efforts by scholars who study the Epstein-Barr virus, herpes viruses 6 and 7, enteroviruses, and many others. CFS may represent a particular response to nonspecific preceding infectious disease.

Pediatric Chronic Fatigue Syndrome - Description and Prevalence

Chronic fatigue syndrome (CFS) is poorly defined in children and most investigations have been summaries of case presentations and small series, rather than pathophysiologic endeavors. Starting with the early reports of Bell and colleagues concerning a group of cases in Lyndonville, NY, numerous studies emanate from facilities around the United States.3

Those studies are nicely summarized in the report generated from a CDC workshop concerning CFS in adolescents. In brief, the reports indicate that pediatric patients with CFS are typically teenage females with severe school absenteeism. As in adults, a large fraction of pediatric patients with CFS report preceding inflammatory conditions but these patients have a better chance of recovery than corresponding adult patients. However, many studies may have incorporated patients who belong to a superset of patients who have CFS-like symptoms and clinical features but who have greatly improved prognosis (see Differential diagnosis). Also, most studies of CFS in the pediatric age range have followed the CDC criteria. However, whether the adult CDC case definition can be applied to children and adolescents is debatable.

To date, the CDC has declined to modify the CFS case definition for the pediatric age group, even when common pediatric findings such as frequent sore throat and swollen glands are included in the criteria; these findings fail to distinguish patients from their otherwise healthy contemporaries. Moreover, the CDC has indicated that CFS is unlikely to occur in patients younger than 10 years. However, establishing the existence of a self-reported illness in younger age groups is difficult and the truth concerning juvenile CFS remains unclear.

Given a relative paucity of studies and some reluctance to conduct large epidemiologic exercises, the fact that estimates of prevalence widely vary and have yet to be accurately determined is not surprising. A range in prevalence of 2 to nearly 300 cases per 100,000 children has been proposed in many studies and some reports of incidence of several percent have been published. Surveys have been performed using various polling techniques and were conducted in different parts of the United States, as well as in other countries. Regional differences in CFS incidence and prevalence may be observed.

Clinical Profile and Differential Diagnosis

The clinical profile of an individual with chronic fatigue syndrome (CFS) is of a high-achieving student or athlete who is usually female (80%), Caucasian, and in the middle-class or upper–middle-class socioeconomic level. This may reflect referral bias but appears consistent throughout most studies.

A familial predisposition (eg, for CFS or related fibromyalgia) has been reported; however, studies to accurately assess genetic factors are only now underway. Preliminary data suggest that the illness is different in boys and girls. An allergic history is common. Milk intolerance is often reported. Children have typically been referred to specialty clinics after extensive screening by their primary care physician has yielded negative or nonspecific test results. Therefore, common short-lived causes of fatigue are effectively excluded. The length of fatigue (ie, 6 mo, according to CDC) also effectively excludes many common illnesses and probably should be retained in any forthcoming pediatric case definition.

As suggested by the term chronic, the clinical course is punctuated by remissions and relapses often triggered by intercurrent infection or stress. The course in adolescents is similar to that in adults. Recently, the 15-year follow-up data from the Lyndonville outbreak were reported and indicated successful resolution in most cases, based on self-assessment measures. However, improvement was often a matter of interpretation on the part of the patients. When questioned further, many had persistence of symptoms but had tailored their lifestyles to the persistent disability.

Differential diagnosis

Careful perusal of the CDC criteria indicates that, essentially, any chronic illness that produces extensive disability in a setting of persistent fatigue may be included in the differential diagnosis. Many of these illnesses are mentioned among the diagnostic exclusions in the Introduction section. However, once such a specific illness has been diagnosed, the diagnosis of CFS then is excluded by definition.

These illnesses certainly include the following:

  • Chronic heart disease
  • Psychiatric illnesses
  • Thyroid disease
  • Connective tissue diseases
  • Chronic anemia
  • Neoplastic disease
  • Chronic infections
  • Endocrine diseases (eg, Addison disease)
  • Inflammatory bowel disease
  • Drug abuse

Note that other chronic illness must be investigated and, in some cases, reinvestigated several times. CFS is, in large measure, a diagnosis of exclusion.

Based on the CDC case definition, no specific physical findings serve to confirm the diagnosis of CFS. CFS is defined by symptoms and not signs. However, adolescents, particularly girls, may have signs and symptoms of postural tachycardia syndrome, including upright and sometimes supine tachycardia, pallor, hypotension, and other vasomotor findings discussed later in this article (see Altered Neurovascular Regulatory Systems in Chronic Fatigue Syndrome).

Varied Pathogeneses Proposed for Chronic Fatigue Syndrome

Investigations into the pathophysiology of chronic fatigue syndrome (CFS) have remained inconclusive, although several possibilities have been suggested. For example, patients may be expected to demonstrate striated muscle deficiencies; however, skeletal muscle energetics, structure, histopathology, physiology, and glycolytic activity have been normal, and electromyographic results have been inconclusive in these patients. In vivo, analyses of muscle energetics are also suggestive of disability but are not definitive and often indicate modest alteration disproportionate to symptomatology.

Cardiovascular studies have not consistently demonstrated defects in day-to-day cardiac fitness in patients with CFS compared with other people who have been deconditioned. Infectious and immune pathologies have been suspect and often, although not consistently, have been related etiologic factors; some studies hint at impaired inflammatory cytokine production and cellular immunity, which may be linked to the symptoms of CFS through changes in neurovascular regulation (see Altered Neurovascular Regulatory Systems in Chronic Fatigue Syndrome).

Progress has been made in 2 seemingly disparate areas of investigation: altered neurovascular regulation and psychological and somatization disorders. Treatment is based on specific pathophysiology. Thus, disabilities that fall within the purview of neurovascular or psychological disorders can be specifically addressed by treatment modalities developed within these respective fields.

Altered Neurovascular Regulatory Systems in Chronic Fatigue Syndrome

Studies of the integrative and regulatory systems have been provocative. Compelling information has been reported concerning abnormalities in the cardiovascular regulatory areas of the brain stem and in other vasoregulatory CNS areas that may be associated with impaired vagal tone, malfunction of central and peripheral nervous systems, an inability to completely activate skeletal muscle, and abbreviated exercise capacity due to inappropriately low heart rate and early fatigue during treadmill testing. Associated neuroendocrine dysfunction, impaired hypothalamic-pituitary-adrenal interactions, and associated neurohumoral findings have been described.

Thus, some evidence suggests a deficit in neuroendocrine regulatory mechanisms that may directly or indirectly limit organ and tissue function through decreased blood pressure (BP) and impaired tissue perfusion. The peripheral circulatory beds and CNS are particularly vulnerable to cardiovascular inadequacy. Maladaptive changes in BP and blood flow can produce many of the signs and symptoms associated with CFS, such as light-headedness, impaired cognition, inappropriate sweating, and temperature instability.

Orthostatic intolerance in adolescents with chronic fatigue syndrome (CFS) is consistent with the postural orthostatic tachycardia syndrome (POTS). Upright posture is a fundamental stressor requiring rapid and effective circulatory and neurologic compensations in order to maintain BP, cerebral blood flow, and effective neurocognitive capabilities. The physiology of upright posture is unique to hominids and cannot be easily studied in animals. Recent investigations lend credence to the hypothesis that CFS results, at least in part, from low upright BP or central blood flow by strongly implicating neurally mediated hypotension, a form of orthostatic intolerance, in the symptomatology of CFS in adults.

In their landmark observations, Rowe and coworkers produced neurally mediated hypotension in 21 of 22 adult patients with CFS using the head-up tilt-table test (HUTTT), a standard orthostatic test that produces enhanced sympathetic tone while decreasing parasympathetic tone in healthy subjects.4 More importantly, treatment of orthostatic intolerance improved symptoms in many patients. These observations have focused on the neurologic aspects of orthostasis and have led some investigators to posit an autonomic defect in CFS. Overt dysautonomia has not been demonstrated. Clues to the nature of orthostatic intolerance in CFS are present in Rowe's earlier work, in which he reported tachycardia often associated with hypotension during orthostasis in adolescents. At least since 1940, orthostatic tachycardia of this sort has been described using many aliases; Streeten referred to orthostatic tachycardia as hyperadrenergic syndrome,5 and Fouad et al described it as idiopathic hypovolemia.6

Orthostatic tachycardia is probably the most common reason for referral to autonomic laboratories for chronic orthostatic intolerance. The syndrome has recently undergone a renaissance as POTS (reported in adults by investigators at the Mayo clinic) and as the syndrome of chronic orthostatic intolerance (reported by the Vanderbilt group). Those who reported the first pediatric cases of POTS demonstrated that orthostatic intolerance during HUTTT in adolescents with CFS is predominantly POTS.

An operational definition of POTS includes symptoms of orthostatic intolerance, such as fatigue, light-headedness, nausea, vomiting, headache, palpitations, and tremulousness, associated with an increased heart rate exceeding 30 beats per minute or a heart rate of more than 120 beats per minute within 10 minutes of HUTTT.

Onset of symptoms often follows an infectious disease and may be related to inflammatory mediators. Some adult and pediatric patients with POTS fulfill CDC criteria for CFS, whereas others do not; however, most patients with non-CFS POTS have symptoms that mimic symptoms of CFS to a lesser extent. Some patients with non-CFS POTS have likely been classified as having CFS. The clinical course of non-CFS POTS is frequently relatively short-lived but may easily exceed 6 months in some patients. Many of the patients with short-lived POTS have little fatigue or exercise intolerance, and some patients remain competitive athletes. Others have a more prolonged course, although without the extent of disability present in many patients with CFS.

A review of patients with delayed orthostatic hypotension (delayed POTS) demonstrated a high degree of association with chronic fatigue. POTS is common and mostly affects females (approximately 80%) aged 12-50 years. Symptoms of orthostatic intolerance in POTS read almost as a litany for CFS, including light-headedness, fatigue, headache, sleep disorders, and neurocognitive difficulties. Preliminary data suggest that autonomic findings may be related to circulatory abnormalities at rest and during orthostasis. Thus, CFS may represent a severe form of POTS in adolescents.

Psychological Aspects of Chronic Fatigue Syndrome

Children and adolescents with chronic fatigue syndrome (CFS), as defined using modified CDC criteria, also demonstrate psychological morbidity. However, this morbidity does not approach the levels observed in control subjects with psychiatric diagnoses. Whether psychological morbidity predates the development of CFS or occurs in reaction to it is controversial, although most authors reject a simple linear psychological model of pathogenesis. Nonetheless, the absence of laboratory markers, failure to implicate a single infectious agent, conflicting immunologic data, and marked discrepancies between symptoms and physical findings continue to lead many health practitioners to conclude that CFS is primarily a psychological disturbance.

Psychiatric syndromes that have been proposed include depression, anxiety disorders, and somatization, all of which have been implicated in adults with CFS. Although some studies in adults suggest that psychiatric illness is more likely to precede the onset of CFS than to follow it, a common etiological pathway has been suggested for both conditions. Some studies demonstrate the premorbid incidence of psychological disturbance in patients with CFS to be similar to that in other general medical populations. Other studies have designated CFS as a psychiatric somatoform disorder, along with conditions such as recurrent abdominal pain. Unfortunately, most studies have been limited by their reliance on retrospective data gathered from patient interviews, chart review, or purely anecdotal conjecture.

Pediatric patients with CFS are less likely to have severe mood-related symptoms compared with patients who are suffering from clinical depression (eg, major depression, dysthymia). These mood-related symptoms include negative affect, suicidal ideation or previous suicidal behavior, externalizing or acting-out behaviors, problems with angry or aggressive behavior, low self-esteem, and feelings of reduced self-efficacy. Thus, research findings with pediatric patients suggest that children and adolescents with CFS are not depressed in the conventional sense. Nevertheless, these patients are psychologically distressed when compared with healthy people of the same age.

Although social and academic activities may be disrupted, children with CFS do not demonstrate the same level of decline in these areas experienced by children with clinical depression. Many children with CFS are high achievers and report dissatisfaction even with above-average performance. Self-esteem and self-concept concerns are less likely to be issues than with depressed youth. Anecdotally, numerous investigators and clinicians have noted that pediatric patients with CFS and their family members are inclined to deny the need for psychological assistance for their personal problems, to minimize the role of stressors in their symptoms, and to reject suggestions that psychological assistance may facilitate their recovery. They generally attribute their symptoms to infectious and immunologic causes, which may be strongly reinforced by the lay literature.

To date, only a few studies have attempted to document the natural history and long-term outcome of pediatric CFS, both in terms of health status and psychosocial morbidity. In general, the physical outcome of CFS in these studies (ie, mean time since initial evaluation; range of 1.6-3.8 y) was favorable, with most patients reporting either resolution or improvement in their symptoms; however, a sizable proportion of these patients reported continued symptoms and significant functional limitations. As in many chronic diseases, children with CFS face significant functional limitations (eg, frequent absences from school, disruptions in social activities, adjustments in family dynamics) surrounding the symptoms and treatment of their illness.

A recent follow-up study of children and adolescents with CFS revealed that although most subjects reported improvements in the number and severity of symptoms (>90% of the sample reported feeling better than they did at the initial assessment, and many believed that they currently did not meet criteria for a formal diagnosis of CFS), many subjects described individual symptoms that persisted as long as 5 years after the onset of illness. This finding is consistent with findings in previous investigations. A large degree of variability was reported in terms of severity of CFS symptoms and outcome, onset of illness, periods of remission and exacerbation of symptoms, health care use and perceived effectiveness, and subsequent diagnoses. In spite of varying improvements in physical status, many subjects reported that their illness had a long-term adverse impact on academic attendance and performance, occupational functioning, and social relationships.

Clearly, a disease this debilitating affects multiple aspects of functioning and development, as well as the life of the family as a whole. Many subjects reported regression via increased dependence in their relationship with their parents because of their physical limitations. The patients spent more time with their parents than the average adolescent or young adult and believed their health status made their parents overprotective and more cautious. At a time when many healthy peers are gaining more freedom and independence from their parents, these families displayed a level of involvement that may have delayed some of these common rites of passage, such as moving out of the home, going away to college, and working full-time.

In terms of their school functioning, many subjects in the study reported cutting back on the hours and days that they spent in class, despite previous successes achieved in the academic arena. Curiously, although many subjects believed that their grades had declined, they still believed that they performed at a level either commensurate with or superior to their classmates. Subjects reported a preference for quieter activities with smaller groups of friends and indicated that they received criticism and disbelief from some peers and teachers regarding the validity of their illness and lengthy absences.

To elucidate the psychological factors operative in patients with CFS, numerous studies have compared case subjects with controls suffering from serious chronic medical conditions, such as multiple sclerosis in adults, childhood cancer, and cystic fibrosis. However, controls like these may not be ideal because patients with these diseases and their parents live with the knowledge that their illness is life threatening; this knowledge can drastically affect perception and interpretation of symptoms.

Studies with more appropriate control subjects (eg, juvenile idiopathic arthritis) revealed that the psychological distress found in pediatric patients with CFS exceeded that found in pediatric patients with juvenile idiopathic arthritis, despite similar patterns of functional disability in both groups. This finding suggests that psychological factors may interact with the characteristics of CFS in a way that plays a more active role in debilitating chronic fatigue in youth than can be explained by the stress of coping with a chronic non–life-threatening illness alone.

At present, the effect of psychological factors in CFS in children and adolescents is unclear. Professionals tend to align themselves with either the organic or the psychological group and accordingly interpret symptoms. Because of the medically oriented providers' frustration with diagnosis and management of CFS, ascribing CFS symptoms to psychological causes or to the sometimes vague field of somatoform illness is appealing. Transcendence of the limited perspective of mind-body dualism is needed to understand and effectively treat patients with CFS.

Integrating psychological factors into models of pathogenesis

Currently, no single model fully explains the pathogenesis of CFS. A simple linear medical model, wherein a single infectious agent causes a specific series of detrimental biologic effects, has not been supported. In more complex models, the final common pathway may be the result of various insults, including viral infection and stress. The consequence of these insults may be immune system activation and dysregulation. The resulting cytokine release and epiphenomena, such as reactivation of latent viruses, contribute to fatigue and associated symptoms.

Very unconvincing support also exists for a simple psychological model, which posits that fatigue is the expression of a primary psychopathologic condition. A more dynamic biopsychosocial model proposes that an acute infectious and/or immunologic event, associated with a physiologic state of fatigue, initiates a cycle in which avoidant behaviors that diminish symptom severity may become associated with various attributional and cognitive factors. Thus, symptoms are attributed to an external agent (eg, virus).

Behaviorally, the patient retreats from a previously active lifestyle into a state of learned helplessness. Because the cause of CFS is perceived to be external and beyond the individual's control, the patient's self-esteem is preserved. Prolonged disability and inactivity may trigger depression and anxiety or exacerbate premorbid psychological symptoms in some individuals. Re-exposure to activity elicits further symptomatic behavior, whereas avoidant behavior further reduces tolerance for physical activity. Repeated (ie, usual, minor) exacerbations via additional viral illnesses or neurovascular instability perpetuate the cycle of symptoms: attribution, avoidance, fatigue, and withdrawal.

The finding that both children and adults with CFS maintain strong convictions that their fatigue is purely physiologic, rejecting psychological explanations, lends some support to this attributional model. A prospective study of patients experiencing a viral illness found that the presence of an attributional style characterized by belief in vulnerability to illness, along with physician indecisiveness in making a diagnosis, predicted which patients developed CFS better than prediction by viral illness factors. Therefore, some psychological factors inherent in patients with CFS may exist and clinicians have yet to understand these factors. These factors result in a differential prolonged response to the initial physical insult and interact with response to treatment approaches such that outcome is more variable despite the potential validity of the physical explanatory model (eg, use of antihypotensive medications for neurally mediated hypotension).

Pathogenetic synthesis

In summary, psychological factors and, more recently, neurovascular factors are active in CFS. Synergism of these factors at the level of the CNS appears likely. Support for these notions is derived from other areas of orthostatic and autonomic study; for example, fluoxetine has been used as highly effective therapy for persons with refractory vasovagal faint, migraine, and panic disorder. Although the pathogenesis of CFS remains unclear, a synthesis of psychology with physiology is attractive.

Treatment

Treatment is otherwise largely supportive and responsive to symptomatology. This includes physical therapy and modest aerobic or anaerobic exercise (if possible) to avoid cardiovascular deconditioning. Sleep may be addressed with medication; often, melatonin or night-time amitriptyline is helpful. If present and severe, pain is often addressed in a pain clinic. Headache may be successfully treated with antimigraine therapy, and biofeedback regimens have been helpful at times. If concurrent with orthostatic intolerance, headache may be amenable to measures designed to improve blood flow and blood pressure (BP). Fatigue and neurocognitive defects are harder to address. Some clinicians have used stimulants, including dexamphetamine and methylphenidate, with some success.

Treatment has remained entirely controversial. Trials of antiviral agents such as poly I: poly C12U (Ampligen) and immunotherapy have been confined to adults. Treatment for orthostatic intolerance may aid approximately 50% of patients. A rehabilitative program of gentle exercise has proved helpful, as has cognitive therapy. A general problem-oriented approach can be helpful in dealing with certain issues such as sleep. Compelling evidence presented by Rowe and Bell at the American Association of Chronic Fatigue Syndrome meeting in January 2001 demonstrated that most children with CFS improve and that improvement is independent of short-term therapy with various agents. Nevertheless, a substantial minority of children have long-term symptoms and morbidity.

Keywords

chronic fatigue syndrome, CFS, chronic fatigue immune dysfunction syndrome, CFIDS, chronic mononucleosis, cognitive difficulties, Da Costa syndrome, Epstein-Barr virus, headache, joint pain, muscle pain, myalgic encephalitis, neurasthenia, pharyngitis, poor sleep, postexercise malaise, postural orthostatic tachycardia syndrome, POTS, sleep disturbance, tender lymphadenopathy, vapors, Gulf War syndrome, thyroid disease

 


More on Chronic Fatigue Syndrome

References
[ CLOSE WINDOW ]

References

  1. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. Dec 15 1994;121(12):953-9. [Medline].

  2. Stewart JM, Gewitz MH, Weldon A, et al. Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics. Jan 1999;103(1):116-21. [Medline].

  3. Bell KM, Cookfair D, Bell DS, et al. Risk factors associated with chronic fatigue syndrome in a cluster of pediatric cases. Rev Infect Dis. Jan-Feb 1991;13 Suppl 1:S32-8. [Medline].

  4. Rowe PC, Bou-Holaigah I, Kan JS, Calkins H. Is neurally mediated hypotension an unrecognised cause of chronic fatigue?. Lancet. Mar 11 1995;345(8950):623-4. [Medline].

  5. Streeten DH. Pathogenesis of hyperadrenergic orthostatic hypotension. Evidence of disordered venous innervation exclusively in the lower limbs. J Clin Invest. Nov 1990;86(5):1582-8. [Medline].

  6. Fouad FM, Tadena-Thome L, Bravo EL, Tarazi RC. Idiopathic hypovolemia. Ann Intern Med. Mar 1986;104(3):298-303. [Medline].

  7. Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. Feb 2003;160(2):221-36. [Medline].

  8. Baker R, Shaw EJ. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ. Sep 1 2007;335(7617):446-8. [Medline].

  9. Bakheit AM, Behan PO, Watson WS, Morton JJ. Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome. Acta Neurol Scand. Mar 1993;87(3):234-8. [Medline].

  10. Barnes PR, Taylor DJ, Kemp GJ, Radda GK. Skeletal muscle bioenergetics in the chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. Jun 1993;56(6):679-83. [Medline].

  11. Bell DS. Chronic fatigue syndrome update. Findings now point to CNS involvement. Postgrad Med. Nov 1 1994;96(6):73-6, 79-81. [Medline].

  12. Bell DS, Bell KM, Cheney PR. Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents. Clin Infect Dis. Jan 1994;18 Suppl 1:S21-3. [Medline].

  13. Bell DS, Jordan K, Robinson M. Thirteen-year follow-up of children and adolescents with chronic fatigue syndrome. Pediatrics. May 2001;107(5):994-8. [Medline].

  14. Blakely AA, Howard RC, Sosich RM, et al. Psychiatric symptoms, personality and ways of coping in chronic fatigue syndrome. Psychol Med. May 1991;21(2):347-62. [Medline].

  15. Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA. Sep 27 1995;274(12):961-7. [Medline].

  16. Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol. Feb 1997;24(2):372-6. [Medline].

  17. Butler S, Chalder T, Ron M, Wessely S. Cognitive behaviour therapy in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. Feb 1991;54(2):153-8. [Medline].

  18. Byrne E, Trounce I. Chronic fatigue and myalgia syndrome: mitochondrial and glycolytic studies in skeletal muscle. J Neurol Neurosurg Psychiatry. Jun 1987;50(6):743-6. [Medline].

  19. Cannon JG, Angel JB, Abad LW, et al. Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome. J Clin Immunol. May 1997;17(3):253-61. [Medline].

  20. Carter BD, Edwards JF, Kronenberger WG, et al. Case control study of chronic fatigue in pediatric patients. Pediatrics. Feb 1995;95(2):179-86. [Medline].

  21. Carter BD, Kronenberger WG, Edwards JF, et al. Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis. Pediatrics. May 1999;103(5 Pt 1):975-9. [Medline].

  22. Cavanaugh RM Jr. Evaluating adolescents with fatigue: ever get tired of it?. Pediatr Rev. Oct 2002;23(10):337-48. [Medline].

  23. Chalder T, Berelowitz G, Pawlikowska T, et al. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147-53. [Medline].

  24. Chambers D, Bagnall AM, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med. Oct 2006;99(10):506-20. [Medline].

  25. Chatterjee T. Chronic fatigue syndrome or myalgic encephalomyelitis in children and adolescents. J Indian Med Assoc. Sep 2003;101(9):544, 547. [Medline].

  26. Chen R, Liang FX, Moriya J, Yamakawa J, Sumino H, Kanda T, et al. Chronic fatigue syndrome and the central nervous system. J Int Med Res. Sep-Oct 2008;36(5):867-74. [Medline].

  27. Cleare AJ, Bearn J, Allain T, et al. Contrasting neuroendocrine responses in depression and chronic fatigue syndrome. J Affect Disord. Aug 18 1995;34(4):283-9. [Medline].

  28. Clements GB, McGarry F, Nairn C, Galbraith DN. Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue. J Med Virol. Feb 1995;45(2):156-61. [Medline].

  29. Cook DB, Nagelkirk PR, Poluri A, Mores J, Natelson BH. The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome. Arthritis Rheum. Oct 2006;54(10):3351-62. [Medline].

  30. Cope H, David A, Pelosi A, Mann A. Predictors of chronic "postviral" fatigue. Lancet. Sep 24 1994;344(8926):864-8. [Medline].

  31. Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome. QJM. Nov 1995;88(11):767-73. [Medline].

  32. Crawley E. Chronic fatigue syndrome in young people: the spectrum and the myths. Br J Hosp Med (Lond). Sep 2006;67(9):452-3. [Medline].

  33. De Lorenzo F, Hargreaves J, Kakkar VV. Possible relationship between chronic fatigue and postural tachycardia syndromes. Clin Auton Res. Oct 1996;6(5):263-4. [Medline].

  34. Demitrack MA, Engleberg NC. Chronic fatigue syndrome. Curr Ther Endocrinol Metab. 1997;6:152-60. [Medline].

  35. DiVasta AD, Alexander ME. Fainting freshmen and sinking sophomores: cardiovascular issues of the adolescent. Curr Opin Pediatr. Aug 2004;16(4):350-6. [Medline].

  36. Edwards RH, Gibson H, Clague JE, Helliwell T. Muscle histopathology and physiology in chronic fatigue syndrome. Ciba Found Symp. 1993;173:102-17; discussion 117-31. [Medline].

  37. Elena Garralda M, Chalder T. Practitioner review: chronic fatigue syndrome in childhood. J Child Psychol Psychiatry. Nov 2005;46(11):1143-51. [Medline].

  38. Feder HM Jr, Dworkin PH, Orkin C. Outcome of 48 pediatric patients with chronic fatigue. A clinical experience. Arch Fam Med. Dec 1994;3(12):1049-55. [Medline].

  39. Freeman R, Komaroff AL. Does the chronic fatigue syndrome involve the autonomic nervous system?. Am J Med. Apr 1997;102(4):357-64. [Medline].

  40. Furlan R, Jacob G, Snell M, et al. Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control. Circulation. Nov 17 1998;98(20):2154-9. [Medline].

  41. Galland BC, Jackson PM, Sayers RM, Taylor BJ. A Matched Case Control Study of Orthostatic Intolerance in Children/Adolescents With Chronic Fatigue Syndrome. Pediatr Res. Dec 10 2007;[Medline].

  42. Garralda ME, Rangel L. Chronic fatigue syndrome of childhood. Comparative study with emotional disorders. Eur Child Adolesc Psychiatry. Dec 2005;14(8):424-30. [Medline].

  43. Grubb BP, Kosinski DJ, Boehm K, Kip K. The postural orthostatic tachycardia syndrome: a neurocardiogenic variant identified during head-up tilt table testing. Pacing Clin Electrophysiol. Sep 1997;20(9 Pt 1):2205-12. [Medline].

  44. Gupta S, Aggarwal S, See D, Starr A. Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome. J Psychiatr Res. Jan-Feb 1997;31(1):149-56. [Medline].

  45. Gur A, Oktayoglu P. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment. Curr Pharm Des. 2008;14(13):1274-94. [Medline].

  46. Heim C, Wagner D, Maloney E, et al. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry. Nov 2006;63(11):1258-66. [Medline].

  47. Hickie I, Davenport T, Wakefield D, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. Sep 16 2006;333(7568):575. [Medline]. [Full Text].

  48. Hickie I, Lloyd A, Wakefield D, Parker G. The psychiatric status of patients with the chronic fatigue syndrome. Br J Psychiatry. Apr 1990;156:534-40. [Medline].

  49. Jacob G, Shannon JR, Black B, et al. Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia. Circulation. Jul 15 1997;96(2):575-80. [Medline].

  50. Jones JF, Maloney EM, Boneva RS, Jones AB, Reeves WC. Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States. BMC Complement Altern Med. 2007;7:12. [Medline].

  51. Jones JF, Nicholson A, Nisenbaum R, et al. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. Dec 2005;118(12):1415. [Medline].

  52. Keenan PA. Brain MRI abnormalities exist in chronic fatigue syndrome. J Neurol Sci. Dec 1 1999;171(1):1-2. [Medline].

  53. Kent-Braun JA, Sharma KR, Weiner MW, et al. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology. Jan 1993;43(1):125-31. [Medline].

  54. Kerr JR, Petty R, Burke B, et al. Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis. April 2008 15;197:1171-84.

  55. Klimas NG, Koneru AO. Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep. Dec 2007;9(6):482-7. [Medline].

  56. Knoop H, Stulemeijer M, de Jong LW, Fiselier TJ, Bleijenberg G. Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: long-term follow-up of a randomized, controlled trial. Pediatrics. Mar 2008;121(3):e619-25. [Medline].

  57. Krilov LR, Fisher M, Friedman SB, et al. Course and outcome of chronic fatigue in children and adolescents. Pediatrics. Aug 1998;102(2 Pt 1):360-6. [Medline].

  58. Kruesi MJ, Dale J, Straus SE. Psychiatric diagnoses in patients who have chronic fatigue syndrome. J Clin Psychiatry. Feb 1989;50(2):53-6. [Medline].

  59. Kuo DZ, Cheng TL, Rowe PC. Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome. Pediatrics. Dec 2007;120(6):e1536-9. [Medline].

  60. Lane RJ, Barrett MC, Taylor DJ, et al. Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord. May 1998;8(3-4):204-9. [Medline].

  61. Lane TJ, Manu P, Matthews DA, et al. Depression and somatization in the chronic fatigue syndrome. Am J Med. Oct 1991;91(4):335-44. [Medline].

  62. Lange G, DeLuca J, Maldjian JA, et al. Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci. Dec 1 1999;171(1):3-7. [Medline].

  63. Lewis SF, Haller RG. Physiologic measurement of exercise and fatigue with special reference to chronic fatigue syndrome. Rev Infect Dis. Jan-Feb 1991;13 Suppl 1:S98-108. [Medline].

  64. Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev. Sep 15 2008;[Medline].

  65. MacLean AR, Allen EV. Orthostatic hypotension and orthostatic tachycardia: treatment with the "head-up bed". JAMA. 1940;115:2162-7.

  66. Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?. Clin Infect Dis. Sep 1994;19(3):448-53. [Medline].

  67. Manu P, Lane TJ, Matthews DA. Chronic fatigue and chronic fatigue syndrome: clinical epidemiology and aetiological classification. Ciba Found Symp. 1993;173:23-31; discussion 31-42. [Medline].

  68. Manu P, Lane TJ, Matthews DA. The frequency of the chronic fatigue syndrome in patients with symptoms of persistent fatigue [published erratum appears in Ann Intern Med 1988 Dec 15;109(12):997]. Ann Intern Med. Oct 1 1988;109(7):554-6. [Medline].

  69. Manu P, Matthews DA, Lane TJ. The mental health of patients with a chief complaint of chronic fatigue. A prospective evaluation and follow-up. Arch Intern Med. Oct 1988;148(10):2213-7. [Medline].

  70. Marshall GS. Report of a workshop on the epidemiology, natural history, and pathogenesis of chronic fatigue syndrome in adolescents. J Pediatr. Apr 1999;134(4):395-405. [Medline].

  71. Marshall GS, Gesser RM, Yamanishi K, Starr SE. Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up. Pediatr Infect Dis J. Apr 1991;10(4):287-90. [Medline].

  72. McComas AJ, Miller RG, Gandevia SC. Fatigue brought on by malfunction of the central and peripheral nervous systems. Adv Exp Med Biol. 1995;384:495-512. [Medline].

  73. McCully KK, Natelson BH. Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clin Sci (Colch). Nov 1999;97(5):603-8; discussion 611-3. [Medline].

  74. McCully KK, Natelson BH, Iotti S, et al. Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. May 1996;19(5):621-5. [Medline].

  75. Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. Apr 2007;26(4):465-73. [Medline].

  76. Montague TJ, Marrie TJ, Klassen GA, et al. Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest. Apr 1989;95(4):779-84. [Medline].

  77. Morillo CA, Klein GJ, Thakur RK, et al. Mechanism of 'inappropriate' sinus tachycardia. Role of sympathovagal balance. Circulation. Aug 1994;90(2):873-7. [Medline].

  78. Moss RB, Mercandetti A, Vojdani A. TNF-alpha and chronic fatigue syndrome. J Clin Immunol. Sep 1999;19(5):314-6. [Medline].

  79. Natelson BH, Johnson SK, DeLuca J, et al. Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis. Clin Infect Dis. Nov 1995;21(5):1204-10. [Medline].

  80. Nijs J, Fremont M. Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications. Expert Opin Ther Targets. Mar 2008;12(3):281-9. [Medline].

  81. Novak V, Novak P. Postural tachycardia syndrome. In: Low PA, ed. Clinical Autonomic Disorders. 2nd ed. Philadelphia, Pa: Lippincott-Raven; 1997:681-99.

  82. Patarca R, Klimas NG, Lugtendorf S, et al. Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis. Jan 1994;18 Suppl 1:S147-53. [Medline].

  83. Paul L, Wood L, Behan WM, Maclaren WM. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol. Jan 1999;6(1):63-9. [Medline].

  84. Pelcovitz D, Septimus A, Friedman SB, et al. Psychosocial correlates of chronic fatigue syndrome in adolescent girls. J Dev Behav Pediatr. Oct 1995;16(5):333-8. [Medline].

  85. Plioplys AV, Plioplys S. Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome. Neuropsychobiology. 1995;32(4):175-81. [Medline].

  86. Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet. Jan 28 2006;367(9507):346-55. [Medline].

  87. Reeves WC, Heim C, Maloney EM, Youngblood LS, Unger ER, Decker MJ. Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study. BMC Neurol. 2006;6:41. [Medline].

  88. Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T. Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study. Pediatrics. Mar 2007;119(3):e603-9. [Medline].

  89. Robertson D. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci. Feb 1999;317(2):75-7. [Medline].

  90. Rosen SG, Cryer PE. Postural tachycardia syndrome. Reversal of sympathetic hyperresponsiveness and clinical improvement during sodium loading. Am J Med. May 1982;72(5):847-50. [Medline].

  91. Russell IJ, Vipraio GA, Michalek JE, et al. Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha. J Interferon Cytokine Res. Aug 1999;19(8):969-78. [Medline].

  92. Saidi G, Haines L. The management of children with chronic fatigue syndrome-like illness in primary care: a cross-sectional study. Br J Gen Pract. Jan 2006;56(522):43-7. [Medline].

  93. Sankey A, Hill CM, Brown J, et al. A follow-up study of chronic fatigue syndrome in children and adolescents: symptom persistence and school absenteeism. Clin Child Psychol Psychiatry. Jan 2006;11(1):126-38. [Medline].

  94. Schikler KN. Potential polygenic influences on chronic fatigue syndrome. Pediatrics. Oct 2006;118(4):1799-800; author reply 1800. [Medline].

  95. Schondorf R, Benoit J, Wein T, Phaneuf D. Orthostatic intolerance in the chronic fatigue syndrome. J Auton Nerv Syst. Feb 15 1999;75(2-3):192-201. [Medline].

  96. Schondorf R, Low PA. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?. Neurology. Jan 1993;43(1):132-7. [Medline].

  97. Schwartz RB, Garada BM, Komaroff AL, et al. Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. AJR Am J Roentgenol. Apr 1994;162(4):935-41. [Medline].

  98. Sisto SA, Tapp W, Drastal S, et al. Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome. Clin Auton Res. Jun 1995;5(3):139-43. [Medline].

  99. Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. Apr 1995;39(3):315-25. [Medline].

  100. Smith MS, Mitchell J, Corey L, et al. Chronic fatigue in adolescents. Pediatrics. Aug 1991;88(2):195-202. [Medline].

  101. Stewart J, Weldon A, Arlievsky N, et al. Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome. Clin Auton Res. Aug 1998;8(4):221-30. [Medline].

  102. Stewart JM, Gewitz MH, Weldon A, et al. Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. J Pediatr. Aug 1999;135(2 Pt 1):218-25. [Medline].

  103. Stokes MJ, Cooper RG, Edwards RH. Normal muscle strength and fatigability in patients with effort syndromes. BMJ. Oct 22 1988;297(6655):1014-7. [Medline].

  104. Straus SE. History of chronic fatigue syndrome. Rev Infect Dis. Jan-Feb 1991;13 Suppl 1:S2-7. [Medline].

  105. Streeten DH, Anderson GH Jr. Delayed orthostatic intolerance. Arch Intern Med. May 1992;152(5):1066-72. [Medline].

  106. Streeten DH, Anderson GH Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. Apr 1998;8(2):119-24. [Medline].

  107. Streeten DH, Anderson GH Jr, Richardson R, Thomas FD. Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling. J Lab Clin Med. Mar 1988;111(3):326-35. [Medline].

  108. Swanink CM, van der Meer JW, Vercoulen JH, et al. Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay. Clin Infect Dis. May 1995;20(5):1390-2. [Medline].

  109. Swanink CM, Vercoulen JH, Galama JM, et al. Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome. J Infect Dis. Feb 1996;173(2):460-3. [Medline].

  110. Taerk GS, Toner BB, Salit IE, Garfinkel PE, Ozersky S. Depression in patients with neuromyasthenia (benign myalgic encephalomyelitis). Int J Psychiatry Med. 1987;17(1):49-56. [Medline].

  111. Takken T, Henneken T, van de Putte E, Helders P, Engelbert R. Exercise testing in children and adolescents with chronic fatigue syndrome. Int J Sports Med. Jul 2007;28(7):580-4. [Medline].

  112. ter Wolbeek M, van Doornen LJ, Kavelaars A, Heijnen CJ. Predictors of persistent and new-onset fatigue in adolescent girls. Pediatrics. Mar 2008;121(3):e449-57. [Medline].

  113. ter Wolbeek M, van Doornen LJ, Kavelaars A, Heijnen CJ. Severe fatigue in adolescents: a common phenomenon?. Pediatrics. Jun 2006;117(6):e1078-86. [Medline].

  114. van de Putte EM, Engelbert RH, Kuis W, et al. How fatigue is related to other somatic symptoms. Arch Dis Child. Oct 2006;91(10):824-7. [Medline].

  115. van de Putte EM, van Doornen LJ, Engelbert RH, et al. Mirrored symptoms in mother and child with chronic fatigue syndrome. Pediatrics. Jun 2006;117(6):2074-9. [Medline].

  116. Viner R, Christie D. Fatigue and somatic symptoms. BMJ. Apr 30 2005;330(7498):1012-5. [Medline].

  117. Viner RM, Clark C, Taylor SJ, et al. Longitudinal risk factors for persistent fatigue in adolescents. Arch Pediatr Adolesc Med. May 2008;162(5):469-75. [Medline].

  118. Visser J, Blauw B, Hinloopen B, et al. CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. J Infect Dis. Feb 1998;177(2):451-4. [Medline].

  119. Vojdani A, Choppa PC, Lapp CW. Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome. J Clin Lab Immunol. 1998;50(1):1-16. [Medline].

  120. Walford GA, Nelson WM, McCluskey DR. Fatigue, depression, and social adjustment in chronic fatigue syndrome. Arch Dis Child. Mar 1993;68(3):384-8. [Medline].

  121. Ware NC. Society, mind and body in chronic fatigue syndrome: an anthropological view. Ciba Found Symp. 1993;173:62-73; discussion 73-82. [Medline].

  122. Wessely S, Powell R. Fatigue syndromes: a comparison of chronic "postviral" fatigue with neuromuscular and affective disorders. J Neurol Neurosurg Psychiatry. Aug 1989;52(8):940-8. [Medline].

  123. Wong R, Lopaschuk G, Zhu G, et al. Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest. Dec 1992;102(6):1716-22. [Medline].

  124. Woods TO, Goldberg DP. Psychiatric perspectives: an overview. Br Med Bull. Oct 1991;47(4):908-18. [Medline].

  125. Wyller VB. The chronic fatigue syndrome--an update. Acta Neurol Scand Suppl. 2007;187:7-14. [Medline].

  126. Wyller VB, Barbieri R, Thaulow E, Saul JP. Enhanced vagal withdrawal during mild orthostatic stress in adolescents with chronic fatigue. Ann Noninvasive Electrocardiol. Jan 2008;13(1):67-73. [Medline].

  127. Wyller VB, Godang K, Morkrid L, et al. Abnormal thermoregulatory responses in adolescents with chronic fatigue syndrome: relation to clinical symptoms. Pediatrics. Jul 2007;120(1):e129-37. [Medline].

  128. Wyller VB, Saul JP, Amlie JP, Thaulow E. Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue. Clin Physiol Funct Imaging. Jul 2007;27(4):231-8. [Medline].

  129. Wyller VB, Saul JP, Walloe L, Thaulow E. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Eur J Appl Physiol. Apr 2008;102(6):623-32. [Medline].

  130. Wyller VB, Thaulow E, Amlie JP. Treatment of chronic fatigue and orthostatic intolerance with propranolol. J Pediatr. Jun 2007;150(6):654-5. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

chronic fatigue syndrome, CFS, chronic fatigue immune dysfunction syndrome, CFIDS, chronic mononucleosis, cognitive difficulties, Da Costa syndrome, Epstein-Barr virus, headache, joint pain, muscle pain, myalgic encephalitis, neurasthenia, pharyngitis, poor sleep, postexercise malaise, postural orthostatic tachycardia syndrome, POTS, sleep disturbance, tender lymphadenopathy, vapors, Gulf War syndrome, thyroid disease

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Coauthor(s)

Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Bryan D Carter, PhD, Professor of Child Psychology in Psychiatry and Behavioral Sciences, Chief Psychologist in Division of Child and Adolescent Psychiatry, Director of Predoctoral Internship in Clinical Child/Pediatric Psychology, Director of Postdoctoral Fellowship Program in Pediatric Psychology, Director of Pediatric Consultation-Liaison Service to Kosair Children's Hospital, University of Louisville School of Medicine
Bryan D Carter, PhD is a member of the following medical societies: American Psychological Association
Disclosure: Nothing to disclose.

Medical Editor

Leonard R Krilov, MD, Chief of Pediatric Infectious Diseases, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital
Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Medimmune Grant/research funds Cliinical trials; Medimmune Honoraria Speaking and teaching; Medimmune Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota School of Medicine
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.