Eosinophilia–myalgia syndrome is a rare, sometimes fatal neurological condition linked to the ingestion of the dietary supplement L-tryptophan. The risk of developing EMS increases with larger doses of tryptophan and increasing age. Some research suggests that certain genetic polymorphisms may be related to the development of EMS. The presence of eosinophilia is a core feature of EMS, along with unusually severe myalgia (muscle pain). Signs and symptoms
The initial, acute phase of EMS, which last for three to six months, presents as trouble with breathing and muscle problems, including soreness and spasm, but which may also be intense. Muscle weakness is not a feature of this phase, but some people experience muscle stiffness. Additional features can include cough, fever, fatigue, joint pain, edema, and numbness or tingling, usually in the limbs, hands and feet.The chronic phase follows the acute phase. Eosinophilic fasciitis may develop, primarily in the limbs. CNS signs may appear, including numbness, increased sensation, muscle weakness, and sometimes cardiac or digestive dysfunction. Fatigue is present to some degree, while the muscle pain (which may be extremely intense) and dyspnea continue in this phase. Causes
Subsequent epidemiological studies suggested that EMS was linked to specific batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko. It eventually became clear that recent batches of Showa Denkos L-tryptophan were contaminated by trace impurities, which were subsequently thought to be responsible for the 1989 EMS outbreak. The L-tryptophan was produced by a bacterium grown in open vats in a Showa Denko fertilizer factory.
The reduction in the amount of activated carbon used and the introduction of the fifth generation Bacillus amyloliquefaciens strain were both associated with the development of EMS, but due to the high overlap of these changes, the precise independent contribution of each change could not be determined (although the bypass of the reverse-osmosis filtration for certain lots was determined to be not significantly associated with the contaminated lots of tryptophan). While Showa Denko claimed a purity of 99.6%, it was noted that "the quantities of the known EMS associated contaminants, EBT and PAA, were remarkably small, of the order of 0.01%, and could easily escape detection". Regulatory response
The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001, but continued to limit the importation of tryptophan not intended for an exempted use until 2005. Diagnosis
Treatment
Treatment is withdrawal of products containing L-tryptophan and the administration of glucocorticoids. Most patients recover fully, remain stable, or show slow recovery, but the disease is fatal in up to 5% of patients. History
The first case of eosinophilia–myalgia syndrome was reported to the Centers for Disease Control and Prevention (CDC) in November 1989, although some cases had occurred as early as 2–3 years before this. In total, more than 1,500 cases of EMS were reported to the CDC, as well as at least 37 EMS-associated deaths.