Information on the following diseases can be found in the Related Disorders section of this report:

• Chronic Epstein-Barr Virus Infection
• Multiple Sclerosis
• Polymyalgia Rheumatica

Usually, the signs and symptoms of CFS/ME appear after a period of time in which the individual has experienced a cold, bronchial distress, hepatitis or intestinal discomfort. Sometimes, the symptoms appear after a bout of fatiguing infectious mononucleosis. In each case, the major symptom is the sudden onset and persistence of profound fatigue. Frequently, patients describe the onset as coming after a period of intense stress.

The fatigue may last for weeks or may come and go over a period of many months. In addition to fatigue, symptoms may include headache, tender lymph nodes, muscle and joint pain, and difficulty in concentrating.

The exact cause of chronic fatigue syndrome/myalgic encephalomyelitis is not known. Researchers believe the disorder may be caused by a viral infection in association with an immune system abnormality. At one time, the Epstein-Barr virus was thought to be implicated in this disorder. However, scientists find high concentrations of Epstein-Barr antibodies (disease-fighting proteins created by the immune system in response to the presence of the virus) in some healthy people, as well as in some people with CFS/ME.

It remains unclear whether the disorder is related to some other virus, one or more environmental pollutants, immune system collapse, or one or more genetic abnormalities. The immune system fails in this disorder, but the cause of the failure is not yet clear.

Myalgic encephalomyelitis appears to affect adults almost exclusively, and it occurs up to three times more often in females than in males.

Symptoms of the following disorders can be similar to myalgic cncephalomyelitis. Comparisons may be useful for a differential diagnosis:

Chronic Epstein-Barr virus Infection is caused by the same virus that causes infectious mononucleosis. Although all individuals who become infected with EBV remain so for the rest of their lives, in most people, the virus becomes and stays inactive when the patient recovers from the initial bout of illness. In chronic EBV infection (CEBV), however, the virus fails to become inactive or is periodically reactivated, so that the patient is chronically or recurrently ill. Medical researchers do not understand the reason for this. Both the nature and the severity of symptoms vary from patient to patient. CEBV can be debilitating, but is not necessarily so. (For more information on Chronic Epstein-Barr Virus Infection, choose "CEBV" as your search term in the Rare Disease Database.)

Multiple sclerosis (MS) is a chronic disorder of the central nervous system which may be progressive, relapsing and remitting, or stable. This disorder is characterized by lesions that may form randomly throughout the brain and spinal cord. These lesions may prevent proper transmission of nerve signals and thus result in a variety of neurological symptoms. Mobility may be impaired and other symptoms such as vision difficulties, speech impairment, abnormal skin sensations and bowel and/or bladder control problems may occur. The exact cause of MS is not known, although researchers believe it may be caused by either an immune system abnormality, or a virus triggered early in life. (For more information on Multiple Sclerosis, choose "MS" as your search term in the Rare Disease Database.)

Polymyalgia rheumatica is a disorder characterized by pain and stiffness in certain muscle groups without causing permanent weakness or atrophy. Symptoms appear quickly and may be most severe in the mornings. Mobility may become impaired after long periods of sitting still. Pain on both sides of the body may develop, and symptoms such as fever, loss of appetite, fatigue, weight loss and depression may occur. Despite severe pain, the muscles may not show any abnormality upon examination. A form of anemia may also be present in some patients. (For more information on Polymyalgia Rheumatica, choose "Polymyalgia Rheumatica" as your search term in the Rare Disease Database.)

Diagnosis
A diagnosis of chronic fatigue syndrome is made when a patient has severe and chronic fatigue for at least six months with other medical conditions having been excluded by clinical diagnosis. Also, four or more of the following should be present for a diagnosis: substantial reduction 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 feelings of dissatisfaction or depression lasting for 24 hours or more after exercise or exertion. These symptoms must be present or have recurred for six or more consecutive months, and must not have been evident prior to the onset of fatigue.

Treatment
Treatment is aimed at relieving the more obvious symptoms and restoring the patient to some level of pre-existing function and well-being. Since the cause of CFS/ME is not known and the course of its development is also unknown, all treatments should be considered cautiously. Most physicians combine some of the treatment options listed below.

Pharmacologic Therapies
Caution and care are necessary in the use of drugs to relieve the symptoms of a chronic disorder whose cause is not known. Patients with diagnosed CFS may be particularly susceptible to drugs affecting the nervous system.

Nonsteroid antiinflammatory drugs may be used to relieve pain. They are generally safe when used as directed but can cause side effects.

Low-dose tricyclic antidepressants have been prescribed to reduce pain and improve sleep. Use of these drugs may also cause adverse side effects of which the patient and physician must be aware.

Other antidepressants including the serotonin reuptake inhibitors have been prescribed in doses lower than those offered to depressed patients. These drugs also must be monitored for adverse side effects.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

The Centers for Disease Control and Prevention (CDC) have released a report on the experimental use of a synthetic, immune system modifier, Ampligen, which yielded modest improvement among CFS patients. Further study is needed of this investigational therapy for chronic fatigue syndrome. The drug is expensive and not reimbursable through health insurance. Adverse side effects have not yet been well defined.

The same CDC report suggests that the experimental use of gamma globulin, corticosteroids and dehydroepiandrosterone were either ineffective or provided temporary relief of symptoms for one month or less.

Research is underway to determine if a Coxsackie B virus associated with stress and amino acid (tryptophan) deficiencies may be implicated in onset of myalgic encephalomyelitis. When the disorder is better understood, scientists may be able to determine a better course of treatment or possibly some method of prevention.

TEXTBOOKS
Larson DE, ed. Mayo Clinic Family Health Book. New York, NY: William Morrow and Company, Inc; 1996:1065.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison’s Principles of Internal Medicine. 14th ed.McGraw-Hill Companies. New York, NY; 1998:2483.

REVIEW ARTICLES
Natelson BH, Lange G. A status report on chronic fatigue syndrome. Environ Health Perspect. 2002;110 Suppl 4:673-77.

Pall MI, Satterle JD. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder. Ann N Y Acad Sci. 2001;933:323-29.

Patarca I. Cytokines and chronic fatigue syndrome. Ann N Y Acad Sci. 2001;933:185-200.

Craig T, Kakumanu S. Chronic fatigue syndrome: evaluation and treatment. Am Fam Physician. 2002;65:1083-90.

Buskila D, Press J. Neuroendocrine mechanisms in fibromyalgia-chronic fatigue. Best Pract Res Clin Rheumatol. 2001;15:747-58.

Whiting P, Bagnall AM, Sowden AJ, et al. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA. 2001;286:1360-68.

FROM THE INTERNET
Mayo Clinic. Chronic fatigue syndrome. 2001:9pp.
http://www.mayoclinic.com

NIAID (National Institute of Allergy and Infectious Diseases) Fact Sheet. Chronic Fatigue Syndrome. 2002:5pp.
www.niaid.nih.gov

Myalgic Encephalomyelitis. 1999:8pp.
http://www.cfs-news.org/me.htm

Basic Introduction to CFS(ME) – (layman’s version). 1999:8pp.
http://Freespace.virgin.net/david.axford/meintrol.htm

Myalgic Encephalomyelitis. BBC News. 1998:3pp.
Http://news.bbc.co.uk/1/hi/health/medical_notes/97509.stm

Hyde B. Nightingale Research Foundation. The clinical and scientific basis of myalgic encephalomyelitis/chronic fatigue syndrome. nd. 2pp.
www.nightingale.ca.nightd.html

Contact a Family. Myalgic Encephalomyelitis. 2001:5pp.
www.cafamily.org.uk/Direct/m51.html

The Myalgic Encephalomyelitis Association of Ontario. About M.E./C.F.S. nd. 2pp.
www.meao-cfs.on.ca/splash.html