Chronic Fatigue Syndrome

Definition
A disorder characterized by debilitating fatigue and several associated physical, constitutional, and neuropsychological symptoms o No single test is diagnostic for chronic fatigue syndrome (CFS). o The U.S. Centers for Disease Control and Prevention (CDC) criteria for CFS are discussed under Diagnostic Approach. In the past, CFS was diagnosed as: o The vapors o Neurasthenia o Effort syndrome o Epidemic neuromyasthenia o Myalgic encephalomyelitis o Multiple chemical sensitivity syndrome o Chronic mononucleosis o Chronic EpsteinBarr virus infection o Postviral fatigue syndrome

Epidemiology

Geographic distribution
o o o

Recognized in many developed countries Most cases arise sporadically. Many clusters have been reported. Los Angeles County Hospital in 1934 Akureyri, Iceland, in 1948 The Royal Free Hospital, London, in 1955 Incline Village, Nevada, in 1985 Incidence/prevalence o Chronic fatigue lasting at least several months is extremely common, but probably only ~15% of these patients meet the CDC criteria for CFS. o Estimates depend on the case definition used and the method of study. o 100300 per 100,000 persons in the U.S. meet the current CDC definition. Sex
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Female-to-male ratio, 2:1

Age Generally in persons 2545 years of age Cases in childhood and in later life have been described.
o o

Risk Factors
No risk factors for CFS have been conclusively identified. Among those suggestedalbeit backed by little compelling dataare: o Genetic predisposition o Social, economic, and educational status o History of childhood abuse o Stress o Various behavioral abnormalities that lead to poor conditioning, weakness, and low energy o Isolation, real or imagined, with inadequate social support

Etiology

Etiology is unknown. Many controversial hypotheses exist. o CFS is often postinfectious. Many studies have attempted to link CFS to infection with EpsteinBarr virus, cytomegalovirus, human herpesvirus type 6, retroviruses, enteroviruses, Candida albicans, Mycoplasma spp., orCoxiella burnetii, among other microbial pathogens, but no clear link has been consistently demonstrated. o Direct viral pathogenesis is unproved and unlikely. o CFS is associated with minor immunologic findings of uncertain significance and sedentary behavior during childhood. In theory, symptoms of CFS could result from excessive production of a cytokine, such as interleukin 1, that induces flulike symptoms. o Compelling data supporting this longheld hypothesis are lacking. o A population-based study from Wichita, Kansas, reported: Differences in gene expression patterns and in candidate gene polymorphisms between patients with CFS and controls These results are controversial and await confirmation. o CFS is commonly accompanied or preceded by neuropsychological symptoms, somatic preoccupation, and/or depression. Some propose CFS is fundamentally a psychiatric disorder and that neuroendocrine and immune disturbances arise secondarily.

In some studies, a form of dysautonomia is suggested by unusual sensitivity to sustained upright tilting, resulting in hypotension and syncope. o Disturbances in the hypothalamic-pituitary-adrenal function have been identified in several controlled studies. Some evidence for normalization in patients whose fatigue abates These neuroendocrine abnormalities could contribute to the impaired energy and depressed mood of patients.
o

Associated Conditions

Depression o Mild to moderate depression is present in one-half to two-thirds of patients. o May be reactive, but prevalence exceeds that seen in other chronic medical illnesses Typically arises suddenly in a previously active person o Fatigue (100%) o Difficulty concentrating (90%) o Headache (90%) o Sore throat (85%) o Tender lymph nodes (80%) o Muscle aches (80%) o Joint aches (75%) o Feverishness (75%) o Difficulty sleeping (70%) o Psychiatric problems (65%) o Allergies (55%) o Abdominal cramps (40%) o Weight loss (20%) o Rash (10%) o Rapid pulse (10%) o Weight gain (5%) o Chest pain (5%) o Night sweats (5%) Infectious o Viral EpsteinBarr virus/mononucleosis HIV Retrovirus Enterovirus Bacterial Lyme disease
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Symptoms & Signs

Differential Diagnosis

o Tuberculosis Endocrine o Adrenal insufficiency o Cushings syndrome o Hypothyroidism o Diabetes Psychiatric o Depression o Bipolar disorder o Anxiety disorder o Somatoform disorders Rheumatologic o Fibromyalgia o Polymyalgia rheumatica o Polymyositis o Dermatomyositis Hematologic/oncologic o Anemia o Lymphoma o Leukemia o Occult cancer Other o Irritable bowel syndrome o Obstructive sleep apnea o Narcolepsy o Alcohol or drug abuse o Iatrogenic Side effects of medications

Diagnostic Approach
Thorough history, physical examination, and judicious use of laboratory tests are required to exclude other causes of the symptoms. CFS has no pathognomonic features and remains a constellation of symptoms and a diagnosis of exclusion. o No laboratory test can diagnose CFS or measure its severity. In most cases, elaborate, extensive workups are not helpful. CDC Criteria for Diagnosis of Chronic Fatigue Syndrome o Clinically evaluated, unexplained, persistent or relapsing fatigue New or definite onset Not the result of ongoing exertion Not alleviated by rest

Results in substantial reduction of previous levels of occupational, educational, social, or personal activities and o 4 of the following symptoms that persist or recur during 6 consecutive months of illness and that do not predate the fatigue Self-reported impairment in short-term memory or concentration Sore throat Tender cervical or axillary nodes Muscle pain Multijoint pain without redness or swelling Headaches of a new pattern or severity Unrefreshing sleep Postexertional malaise lasting 24 hours

Laboratory Tests
No laboratory test can diagnose this condition or measure its severity. Extensive laboratory testing is usually not warranted. In most patients, complete blood count, thyroid stimulating hormone, erythrocyte sedimentation rate, and basic chemistry profile are useful to rule out other common etiologies of fatigue.

Imaging
Claims that MRI or single-photon emission CT can identify abnormalities in the brain of patients with CFS have not withstood further study.

Diagnostic Procedures
A sleep study can be useful to rule out sleep apnea, restless leg syndrome, and other sleep disorders that may cause chronic fatigue.

Treatment Approach
After other illnesses have been excluded, there are several points to address with respect to long-term care: o Patient education Inform about the illness and what is known of its pathogenesis. Potential impact on the physical, psychological, and social dimensions of life Prognosis, emphasizing that the condition is not a progressive one and does not adversely impact life expectancy o Treatment of specific symptoms o Practical advice regarding lifestyle o Physician support of patients efforts to recover

Comprehensive approach to physical, psychological, and social aspects of well-being o Both cognitive therapy and a gently accelerating exercise program have been shown to improve the symptomatology and functioning of some patients with CFS.

Specific Treatments
Symptomatic treatment NSAIDs o Indications Headache Diffuse pain Feverishness Antihistamines or decongestants o Indications Allergic rhinitis Sinusitis Nonsedating antidepressants o Indications Depression Anxiety Medications of no value o Acyclovir o Fludrocortisone o Galantamine o Modafinil o Intravenous immunoglobulin Controversial medications o Low-dose hydrocortisone Provide modest benefit, perhaps merely due to activating effects May lead to adrenal suppression o Stimulants (e.g., amphetamines) Little data to support their use

Lifestyle modification Heavy meals with alcohol and caffeine at night can make sleep more elusive, compounding fatigue. Total bed rest leads to deconditioning and the self-image of being chronically debilitated. Overexertion may worsen exhaustion and lead to total avoidance of exercise.

A moderate, carefully graded exercise regimen has been proved to relieve symptoms and enhance exercise tolerance.
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Cognitive behavioral therapy Goal: to dispel misguided beliefs and fears about CFS that can contribute to inactivity and despair

Monitoring

Periodic reassessment to: o Identify an underlying process that is late in declaring itself o Address intercurrent symptoms that should not be dismissed as yet another subjective symptom

Complications
Isolation, frustration, and resignation can mark the protracted course of illness. o Patients may become angry at physicians for failing to acknowledge or resolve their plight. o Many patients are frequent visitors to their doctors offices and often are demanding of expensive additional testing that is almost always useless. No known medical complications of CFS

Prognosis

Natural history o Once the pattern of illness is established, symptoms may fluctuate. o Many patients report diverse symptoms that are linked; i.e., during periods of greatest fatigue they perceive the most pain and difficulty with concentration. o Exacerbating factors Excessive physical or emotional stress o Functional status Most remain capable of meeting family, work, or community obligations despite symptoms; discretionary activities are abandoned first. Some feel unable to engage in gainful employment. A minority of patients require help with activities of daily living. o Does not appear to progress o Many patients experience gradual improvement. o Only a minority of patients recover fully. No known means of prevention

Prevention

ICD-9-CM
780.71 Chronic fatigue syndrome Chronic Fatigue Syndrome

See Also Internet Sites

Professionals o Chronic Fatigue Syndrome U.S. Centers for Disease Control and Prevention o Chronic Fatigue Syndrome: Evaluation and Treatment American Family Physician Patients o Chronic Fatigue Syndrome MayoClinic.com o Chronic Fatigue Syndrome MedlinePlus

Depression Fibromyalgia

General Bibliography
Afari N, Buchwald D: Chronic fatigue syndrome: a review. Am J Psychiatry160:221, 2003 [PMID:12562565] Baker R, Shaw EJ: Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ 335:446, 2007 [PMID:17762037] Cleare AJ et al: Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J Clin Endocrinol Metab 86:3545, 2001 [PMID:11502777] Prins JB, van der Meer JW, Bleijenberg G: Chronic fatigue syndrome. Lancet367:346, 2006 [PMID:16443043] Reid S et al: Chronic fatigue syndrome. Clin Evid , 2004 [PMID:15865734] Ross SD et al: Disability and chronic fatigue syndrome: a focus on function.Arch Intern Med 164:1098, 2004 [PMID:15159267] Vernon SD, Reeves WC: The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Pharmacogenomics7:345, 2006 [PMID:16610945] Viner R, Christie D: Fatigue and somatic symptoms. BMJ 330:1012, 2005 [PMID:15860829] Whiting P et al: Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA 286:1360, 2001 [PMID:11560542]

This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 384 Chronic Fatigue Syndrome by SE Straus.

PEARLS
CFS has no pathognomonic features and remains a constellation of symptoms and a diagnosis of exclusion after medical etiologies are ruled out. No clear etiology for CFS has been demonstrated, and direct viral effects are unproved.