Eosinophilia-Myalgia Syndrome

Updated: Jan 12, 2021
  • Author: William E Monaco, MD; Chief Editor: Herbert S Diamond, MD  more...
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Practice Essentials

Eosinophilia-myalgia syndrome (EMS) was first identified in 1989, when approximately 1500 patients developed subacute onset of myalgias and peripheral eosinophilia. They then went on to have chronic muscle, fascia, nerve, and skin involvement. The Centers for Disease Control and Prevention (CDC) proposed a surveillance case definition that included the following [1, 2] :

  • Incapacitating myalgias
  • Peripheral eosinophil count greater than 1000/µL
  • No evidence of infection (ie, trichinosis) or neoplasm

Studies quickly linked EMS to dietary supplements that contained L-tryptophan, a supplement commonly used by patients with fibromyalgia syndrome (FMS), which was made using genetically engineered bacteria. [3, 4, 2, 5] Specifically, the analysis found an impurity identified as 1’1’-ethylidenebis[tryptophan] (EBT), in L-tryptophan manufactured by a single company. [6]  This supplement was quickly removed from the market, resulting in swift resolution of the EMS epidemic, but unfortunately there were over 30 deaths in just 6 months.

Since then, other causes of EMS have been implicated. Six other impurities in L-tryptophan have been associated with EMS, including 3-(phenylamino) alanine (PAA), which shares similar properties with 3-(N-phenylamino)-1,2-propanediol (the chemical found in rapeseed oil and implicated in the 1981 Spanish toxic oil syndrome epidemic [7] ). [8]

An investigator injected himself with quinolinic acid, an L-tryptophan metabolite, and developed peripheral eosinophilia and subcutaneous inflammatory lesions resembling eosinophilic fasciitis. [9]

Also, 14% of EMS cases occurred in patients who had not taken L-tryptophan, suggesting that other agents (eg, probiotics) can also trigger this disease. [10, 11] Since the FDA lifted the ban on L-tryptophan, rare case reports of EMS have been reported.

In 2001, new diagnostic criteria for EMS were proposed that identified the following two patterns of presentation. 

  • Abrupt onset of peripheral eosinophilia, myalgia, and at least one of the following: rash, edema, pulmonary involvement, or neuropathy.

  • One of the following occurring within 24 months of an acute illness: 1) fasciitis, neuropathy, and myalgia or muscle cramps or 2) any three or more of: fasciitis, myopathy, neuropathy, or peripheral eosinophilia

Diagnosis with the new criteria requires exclusion of trichinosis; vasculitis; and infectious, allergic, neoplastic, or connective tissue disease that could explain the patient’s symptoms. [1]



The exact pathophysiology of EMS remains unknown. It is thought to involve exposure to certain substances in a genetically susceptible host that ultimately triggers acute inflammation, eosinophil activation/degranulation, and chronic tissue fibrosis. Analysis of the deep dermis shows evidence of local fibroblast activation, increased expression, of type I and VI collagen, and elevated levels of transforming growth factor β (TGFβ). Levels of interleukin (IL)-2, IL-4, IL-5, interferon (INF) gamma, and granulocyte-monocyte colony stimulating factor (GMCSF) are increased in patients with EMS. [12, 13, 3, 14]



United States

During the initial epidemic, over 1500 cases of EMS were confirmed in the United States. However, estimates indicate that 5,000-10,000 people had this disease. [15]  Since 1991, reports of EMS are limited to case reports only, most recently in 2011. [16]


EMS also occurred in other parts of the world, including the United Kingdom, France, Israel, Japan (12 patients), western Germany (69 patients), and Canada (10 patients). Cohort studies performed during the epidemic estimated that the attack rate of EMS among users of L-tryptophan was 0.5%-9%, depending on the product lot of the L-tryptophan ingested.


By July 1991, 36 deaths were attributed to EMS. The mortality rate ranged from 2% in national surveillance data to 6% in some cohorts. Most deaths were the result of neurogenic complications such as ascending polyneuropathy, cardiopulmonary disease, or superimposed infection. [17]

Of the patients with an acute presentation of EMS, 34% required hospitalization for incapacitating myalgias, muscle cramps, or pulmonary involvement.

Race, Sex, and Age-related Demographics

Demographic characteristics of the patients reported to have EMS were as follows:

  • 97% white
  • 84% female
  • Most were 35-60 years old (age range 17-81 years, mean 49 years)