What Is Eosinophilia-Myalgia Syndrome?

Eosinophilia-myalgia syndrome (EMS) is a rare disorder in which white blood cells known a eosinophils build up in the body, causing inflammation in different areas including the muscles, skin, and lungs. Eosinophilia-myalgia syndrome can cause symptoms like itchy rash, fatigue, and joint pain, but also serious complications like irregular heartbeat and memory issues. It can even be fatal.

There is no test for EMS, so it may be misdiagnosed as a condition with similar symptoms such as fibromyalgia or lupus. And while eosinophilia-myalgia syndrome has long been linked to L-tryptophan—an amino acid available in supplement form, the disorder has also been diagnosed in people without a history of using these products.

This article explains EMS and its symptoms, as well as its potential causes. It also discusses how eosinophilia-myalgia syndrome is diagnosed and the treatment options.

Causes of Eosinophilia-Myalgia Syndrome

Eosinophilia-myalgia syndrome (EMS) first emerged in the United States in October 1989 when three women in New Mexico sought treatment for similar symptoms. The epidemic eventually included 1,500 people and caused 37 deaths.

L-Tryptophan Supplements

L-tryptophan naturally occurs in certain foods, but during the 1989 epidemic the symptoms of severe muscle pain with elevated eosinophil levels were linked to synthetic L-tryptophan products.

Patients reported taking the supplement for stress, depression, premenstrual syndrome (PMS), and other reasons. In 1990, the Food and Drug Administration recalled all L-tryptophan supplements because of the link to EMS.

Scientists have since concluded that the cause of the 1989 outbreak was not the L-tryptophan itself, but contaminants introduced during the manufacturing process. After 1994, synthetic L-tryptophan was again legal to sell and manufacture in the U.S.

Other Supplements

Not all known cases of EMS are associated with L-tryptophan. Although evidence is based on only a handful of cases from the time of the 1989 outbreak, there may also be a relationship between EMS and other supplements such as:

• Niacin
• Lysine
• Hydroxytryptophan

The National Institutes of Health (NIH) has also warned of other eosinophilia-myalgia syndrome cases associated with the supplement 5-HTP, which is chemically similar to L-tryptophan and may contain similar contaminants. The NIH advises using 5-HTP with caution.

Genetics

Some researchers think people who develop eosinophilia-myalgia syndrome may be geneticly predisposed to developing disorders related to the body's ability to metabolize tryptophan. 

Other Risk Factors

Studies also suggested that most people who took the supplement were susceptible to getting EMS, with the risk increasing with quantity consumed. Older age also appears to make the risk of developing EMS higher.

Symptoms of EMS

The most common symptom of eosinophilia-myalgia syndrome is generalized, severe muscle pain that tends to worsen over weeks and may cause muscle spasms. Symptoms tend to begin suddenly and range from mild to severe. The condition can cause life-threatening complications and may result in death.

Eosinophilia-myalgia syndrome goes through acute and chronic phases that share symptoms of muscle pain and fatigue. The acute phase may last anywhere between three and six months, with common symptoms of skin changes and muscle pain in the arms and legs.

The skin of those affected may swell, thicken, or harden as they develop eosinophilic fasciitis. People who have this condition over a long time may also develop impaired function in affected joints.

During the chronic phase, symptoms appear to flare. They may act up for a period of time and then go into remission. Overall symptoms of eosinophilia-myalgia syndrome in this phase include:

• Swelling of the arms and legs, and sometimes the face
• Joint pain
• An extremely itchy skin rash
• A cough and shortness of breath
• Fatigue
• Fever
• Patchy hair loss (alopecia)
• Bladder issues
• Behavioral changes (irritability, mood changes)
• Cognitive difficulties (memory issues, trouble concentrating)
• Digestive issues (nausea, vomiting, cramping)
• Heart abnormalities (inflammation, irregular heartbeat)

Digestive and cardiac issues are more likely to occur during this phase as well.

How is Eosinophilia-Myalgia Syndrome Diagnosed?

The eosinophilia-myalgia syndrome diagnosis is difficult, and there are no available tests used to confirm EMS. The criteria established by the Centers for Disease Control and Prevention (CDC) in the wake of cases linked to L-tryptophan use include:

• A blood draw with elevated eosinophil counts of 1,000 cells or more per cubic millimeter (mm3)
• Severe muscle pain that limits daily activities
• Exclusion of any infection or other cause of the pain with elevated eosinophils

In addition to conducting a physical exam and running blood tests, your healthcare provider must consider all factors related to your personal health history, especially medication use.

In the developed world, medication is the most common cause of elevated eosinophils (eosinophilia), so it's important to rule out other drug responses before diagnosing eosinophilia-myalgia syndrome.

Some of the drugs that can cause eosinophilia include:

• Antibiotics (penicillin, cephalosporins)
• Non-steroidal anti-inflammatory medications (aspirin, ibuprofen)
• Anti-seizure drugs (phenytoin)
• Gout medication (allopurinol)

More rarely a severe form of response occurs, called drug reaction with eosinophilia and systemic symptoms (DRESS). Antibiotics and anti-seizure drugs, as well as antivirals used to treat human immunodeficiency virus (HIV) infection, are most often linked to serious DRESS episodes.

Treatment

The most important step in treating EMS is discontinuing the supplement that triggered it. In people with mild symptoms, this is sometimes all that is necessary. For most people, however, it is not enough to simply stop taking the supplement.

There is no evidence-based standard of care for eosinophilia-myalgia syndrome that's been fully researched and adopted by medical professions. For this reason, treatment is tailored to each individual.

Medication

Among the medications used to treat symptoms of eosinophilia-myalgia syndrome are:

• Muscle relaxants are used to treat similar conditions like fibromyalgia and may also help people with EMS. They are believed to increase the effects of a neurotransmitter that reduces pain signals in the brain.
• NSAIDs to treat pain, though these are not always helpful, especially in people with severe symptoms
• Diuretic drugs to reduce fluid retention
• Corticosteroid drugs such as prednisone, to reduce inflammation

During the 1989 outbreak, some patients treated with the anti-cancer drug methotrexate reported improvement in major symptoms like fatigue, edema, and muscle symptoms. 

A follow-up study two years after the outbreak found that prednisone was the only treatment that seemed to be helpful in the early stages of the disease, with 79% of patients reporting improvement.

Lifestyle Changes

People living with eosinophilia-myalgia syndrome may need to make lifestyle changes. While little is known about long-term impacts and life expectancy, staying as physically active as possible appears to offer some benefits. Be sure to discuss diet, exercise, and other lifestyle changes with your healthcare provider.

Prognosis

For most people, EMS is a chronic condition. A 1995 study found that only around 6% of those who developed EMS during the 1989 outbreak were well 3.6 years later. Around 21% reported improvement, but 65% said their symptoms were either unchanged or worse. Symptoms most likely to linger include muscle pain, joint pain, fatigue, and cognitive impairment.

Summary

Eosinophilia-myalgia syndrome is a chronic condition that has been linked to the use of the supplement L-tryptophan. A contaminant present in this supplement is believed to have been responsible for the 1989 outbreak. A few other related supplements have also been implicated in the disease.

People with EMS experience symptoms such as severe muscle pain, fatigue, and cognitive problems. For most people, the condition is chronic and symptoms will continue for years after onset.

Some medications such as corticosteroids may help people with EMS. Lifestyle changes can also help.