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Eosinophilia-Myalgia Syndrome

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Copyright 1990, 1991, 1992, 1999, 2013

NORD is very grateful to Gerald J. Gleich, MD, Professor of Dermatology and Medicine, Department of Dermatology, University of Utah, for assistance in the preparation of this report.

Synonyms of Eosinophilia-Myalgia Syndrome

Disorder Subdivisions

General Discussion

Summary
Eosinophilia-myalgia syndrome is a rare disorder that affects multiple organ systems of the body including the muscles, skin, and lungs. The onset of the disorder is often abrupt and the specific symptoms can vary greatly from one person to another. Common symptoms include muscle pain (myalgia), muscle weakness, cramping, skin rashes, difficulty breathing (dyspnea) and fatigue. Affected individuals have elevated levels of certain white blood cells known as eosinophils in the various tissues of the body, a condition known as eosinophilia. Eosinophilia-myalgia syndrome can potentially cause severe, disabling complications and even death.

Introduction
The eosinophilia-myalgia syndrome occurred as an epidemic in 1989 and occurrence of the syndrome was traced to L-tryptophan produced by one Japanese company, Showa Denko KK. Most individuals who developed eosinophilia-myalgia syndrome had ingested contaminated L-tryptophan, a dietary amino acid supplement often sold in health food stores before being pulled from the market in 1990. However, contaminated L-tryptophan does not account for all cases of eosinophilia-myalgia syndrome suggesting that other environmental agents may cause the disorder. Very few cases of EMS have been identified since the 1989 epidemic.

Symptoms

The symptoms and severity of eosinophilia-myalgia syndrome can vary greatly from one person to another. In most cases, the onset of the disorder is rapid.

The initial symptoms associated with eosinophilia-myalgia syndrome include breathing difficulties such as shortness of breath (dyspnea) and muscle aches, cramping and spasms. Muscle pain (myalgia) also occurs and may become progressively worse. Eventually, muscle pain may become incapacitating making it difficult to walk or perform daily activities. The muscles of the legs, back and shoulders are most often affected. Muscle spasms may be triggered by movement or exercise. Muscle weakness usually does not occur until later in the course of the disorder.

Additional symptoms that often occur during this earlier phase of eosinophilia-myalgia syndrome include cough, fever, fatigue, joint pain (arthralgia), swelling due to the abnormal accumulation of fluid (edema), and a sensation of numbness or tingling, most often in the hands, feet, arms or legs. Affected individuals may also develop a rash that can be extremely itchy (pruritus). This initial (acute) phase of the disorder usually lasts approximately 3-6 months.

After this initial phase, affected individuals experience chronic symptoms that can affect several different organ systems of the body. The skin is the organ most often affected and may slowly swell, thicken and harden (eosinophilic fasciitis). The arms and legs are most often affected. Some individuals develop small areas of hair loss (alopecia).

The central nervous system becomes involved in some cases and can cause decreased feeling (sensation) in the hands, increased sensation (hyperesthesia) in the back and arms or legs, progressive muscle weakness, bladder dysfunction, changes in mood or behavior and cognitive deficits such as memory loss, difficulty concentrating and difficulty communicating. However, the relationship between cognitive deficits or behavioral changes and eosinophilia-myalgia syndrome is controversial. Some researchers believe these problems arise from severe pain, depression and disturbances in sleep patterns associated with eosinophilia-myalgia syndrome and not from the direct, underlying effects of the disorder.

Additional symptoms can occur during the chronic phase of eosinophilia-myalgia syndrome although they occur less often than the abovementioned symptoms. Such symptoms include heart (cardiac) abnormalities including inflammation of the heart muscle (myocarditis), irregular heartbeats (arrhythmias) and palpitations. Some individuals may have gastrointestinal symptoms including nausea, vomiting, diarrhea and abdominal pain.

Muscle pain, the characteristic finding of the acute phase, also occurs during the chronic phase of the disorder, although it often comes and goes (remission and relapse). Fatigue, which can be profound, also occurs during the chronic phase. Muscle cramps and shortness of breath are also present.

Causes

The exact cause of eosinophilia-myalgia syndrome is unknown. Most cases of the disorder occurred during an outbreak in 1989 and were linked to the consumption of L-tryptophan. Researchers determined that this outbreak was due to contaminated L-tryptophan that had been manufactured by Showa Denko KK in Japan.

Tryptophan is an essential amino acid present in very small quantities in most foods. However, the amounts ingested by individuals with eosinophilia-myalgia syndrome are over and above the amounts that naturally occur in food. Tryptophan was formerly available at health food stores without prescription as a dietary supplement. Although there was no proof of effectiveness, many individuals used it to treat depression, anxiety, premenstrual syndrome and insomnia. During 1990, the Food and Drug Administration (FDA) had tryptophan withdrawn from the shelves of stores.

Although most cases of eosinophilia-myalgia syndrome have been linked to contaminated L-tryptophan, many individuals who ingested products containing the contaminated tryptophan did not develop the disorder. Researchers believe that additional factors including genetic, environmental and immunologic factors are necessary for the development of eosinophilia-myalgia syndrome.

Almost all cases of eosinophilia-myalgia syndrome were traced back to ingestion of contaminated L-tryptophan from SDKK LT. There are reports in the medical literature of individuals who developed symptoms extremely similar to those found in eosinophilia-myalgia syndrome after ingesting other nutritional supplements including 5 hydroxytryptophan, L-lysine and niacin.

A key finding in eosinophilia-myalgia syndrome is eosinophilia or widespread inflammation. Eosinophilia is a medical term for when a person has abnormally high levels of eosinophils in the body. Eosinophils are specialized white blood cells most often associated with allergies and parasitic infection. Eosinophils consume and destroy foreign substances in the body and help to regulate the body’s inflammatory response to disease. However, when too many eosinophils are present they can damage tissue and cause symptoms. The exact role that the abnormally high numbers of eosinophils play in the development and progression of eosinophilia-myalgia syndrome is unknown, although evidence shows that toxic eosinophil granule proteins were released in damaged tissues.

Affected Populations

Eosinophilia-myalgia syndrome was first reported in 1989 after three people in New Mexico were identified with the disorder. The exact incidence of eosinophilia-myalgia syndrome is unknown. One estimate indicates that anywhere from 5,000-10,000 people have developed the disorder. Most reported individuals have been females and were from the United States. However, eosinophilia-myalgia syndrome has been reported in other countries as well including Germany, Canada and the United Kingdom

Related Disorders

Symptoms of the following disorders can be similar to those of eosinophilia-myalgia syndrome. Comparisons may be useful for a differential diagnosis.

Eosinophilic fasciitis is a rare disorder characterized by inflammation of the tough band of fibrous tissue beneath the skin (fascia). The arms and legs are most often affected. Inflammation is caused by the abnormal accumulation of certain white blood cells including eosinophils in the fascia. Eosinophilic fasciitis eventually causes the skin to swell and slowly thicken and harden (induration). The disorder most commonly affects middle-aged adults. The exact cause of eosinophilic fasciitis is unknown. Some researchers believe that eosinophilic fasciitis is a variant of scleroderma (systemic sclerosis), an autoimmune connective tissue disorder characterized by hardening of the skin. Eosinophilic fasciitis commonly afflicted EMS patients. (For more information on this disorder, choose “eosinophilic fasciitis” as your search term in the Rare Disease Database.)

Toxic oil syndrome is a rare disorder that occurred in Spain in the early 1980s. Affected individuals developed a variety of symptoms including shortness of breath (dyspnea), cough, chest pain, headaches, and fever. Additional symptoms occurred in some cases including abdominal pain, difficulty swallowing (dysphagia), nausea, a skin rash, itching (pruritus), a rapid heartbeat (tachycardia), an abnormally enlarged liver (hepatomegaly) and an abnormally enlarged spleen (splenomegaly). Eventually, affected individuals develop severe muscle pain and cramps. Affected individuals also had abnormally high levels of eosinophils (a type of white blood cell) in the body (eosinophilia). Toxic oil syndrome was caused by rapeseed oil, which was intended for industrial use, but fraudulently sold as olive oil. Researchers believe that toxins found in the rapeseed oil (as part of the refinement process), such fatty acid compounds (anilides), caused the symptoms of the disorder.

Eosinophilic disorder is a general term for any disorder characterized by infiltration of the skin and tissue by a certain type of white blood cell called eosinophils, including disease resulting from arthropod bites, infections, and drug reactions. Churg-Strauss syndrome, hypereosinophilic syndrome and eosinophilic cellulitis are examples of disorders characterized by elevated levels of eosinophils. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
A diagnosis of eosinophilia-myalgia syndrome is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. In 2001, specific criteria were proposed for diagnosing eosinophilia-myalgia syndrome (Hertzman, et al. 2001). A diagnosis is made if the criteria for either of two different patterns are fulfilled.

Pattern 1:
Presence of a documented illness of abrupt or relatively discreet onset accompanied by evidence, in the absence of the exclusions noted below, of all three of the following manifestations within six months of onset: (1) eosinophilia (2) myalgia (3) at least one of rash, edema, pulmonary involvement, or neuropathy.

Pattern 2:
Presence of an illness, with or without a documented early episode, accompanied by one of the following combinations of manifestations, in the absence of the exclusions noted below, occurring within 24 months of illness onset: (1) fasciitis, neuropathy, and myalgia or muscle cramps or (2) any three or more of fasciitis, myopathy, neuropathy, or eosinophilia (within six months of onset).

Exclusions:
Eosinophilia-myalgia syndrome should not be diagnosed within the presence of trichinosis, vasculitis, or any other documented infectious, allergic, neoplastic, connective tissue, or other type of disease that could adequately explain the clinical manifestations.

Many of the tests performed to diagnose eosinophilia-myalgia syndrome are done to rule out other conditions. Such tests include a complete blood count, x-ray studies, pulmonary function tests and electromyography, a test that evaluates the health and function of muscles and the nerves that control muscles.

Treatment
The treatment of eosinophilia-myalgia syndrome is symptomatic and supportive. Affected patients should stop taking any product with L-tryptophan or another potential causative agent. High-dose corticosteroid therapy may be necessary in some cases, particularly in individuals who are seriously ill. Corticosteroid therapy is beneficial to many individuals, but does treat all of the symptoms associated with the disorder.

Additional therapies include non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, diuretics and pain medications (analgesics) may be beneficial in some cases.

Investigational Therapies

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

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

Organizations related to Eosinophilia-Myalgia Syndrome

References

JOURNAL ARTICLES
Fernstrom JD. Effects and side effects associated with the non-nutritional use of tryptophan by humans. J Nutr. 2012;142:2236S-2244S. http://www.ncbi.nlm.nih.gov/pubmed/23077193

Valent P, Klion AD, Rosenwasser LJ, et al. ICON: eosinophil disorders. World Allergy Organ J. 2012;5:174-181. http://www.ncbi.nlm.nih.gov/pubmed/23282419

Allen JA, Peterson A, Sufit R, et al. Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan. Arthritis Rheum. 2011;63:3633-3639. http://www.ncbi.nlm.nih.gov/pubmed/21702023

Margolin L. Non-L-tryptophan related eosinophilia-myalgia syndrome with hypoprotinemia and hypoalbuminemia. J Rheumatol. 2003;30:628-629. http://www.ncbi.nlm.nih.gov/pubmed/12610828

Hertzman PA, Clauw DJ, Duffy J, Medsger TA Jr., Feinstein AR. Rigorous new approach to constructing a gold standard for validating new diagnostic criteria, as exemplified by the eosinophilia-myalgia syndrome. Arch Intern Med. 2001;161:2301-2306. http://www.ncbi.nlm.nih.gov/pubmed/11606145

Kamb ML, Murphy JJ, Jones JL, et al. Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients. JAMA. 1992;267:77-82. http://www.ncbi.nlm.nih.gov/pubmed/1727200

Pollina DA, Kauffman LD, Masur DM, Krupp LB. Pain, fatigue and sleep in eosinophilia-myalgia syndrome: relationship to neuropsychological performance. J Neuropsychiatry Clin Neurosci. 1998;10:338-342. http://www.ncbi.nlm.nih.gov/pubmed/9706542

Haseler LJ, Sibbitt WL Jr., Sibbitt RR, Hart BL. Neurologic, MR imaging, MR spectroscopic findings in eosinophilia myalgia syndrome. AJNR Am J Neuroradiol. 1998;19:1687-1994. http://www.ncbi.nlm.nih.gov/pubmed/9802492

Martin RW, Duffy J, Engel AG, et al. The clinical spectrum of eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology. Ann Intern Med. 1990;113:124-134. http://www.ncbi.nlm.nih.gov/pubmed/2360751

Hertzman PA, Blevins WL, Mayer J, et al. Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan. N Engl J Med. 1990;322:869-873. http://www.ncbi.nlm.nih.gov/pubmed/2314421

FROM THE INTERNET
Medsger Jr. TA, Ahmed MM, Mubashir E, Sairam S. Eosinophilia-Myalgia Syndrome. Emedicine Journal, January 19, 2012. Available at: http://emedicine.medscape.com/article/329614-overview Accessed on: July 20, 2013.

Schwartz RA. Dermatological Manifestations of Eosinophilia-Myalgia Syndrome. Emedicine Journal, September 17, 2012. Available at: http://emedicine.medscape.com/article/1066811-overview Accessed on: July 20, 2013.

Report last updated: 2011/10/11 00:00:00 GMT+0