L-tryptophan and the eosinophilia-myalgia syndrome: current understanding of the etiology and pathogenesis.
The eosinophilia-myalgia syndrome (EMS) is a newly recognized illness that occurred in an epidemic form during the summer of 1989. The illness was characterized in the acute phase by myalgia and eosinophilia, followed in many patients by chronic cutaneous lesions, progressive neuropathy, and myopathy. EMS was associated with ingestion of L-tryptophan, an essential amino acid marketed as a nutritional supplement but widely used as a therapeutic agent. Evidence of abnormal L-tryptophan metabolism has been described in patients with EMS, and most likely reflects increased activity of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan metabolism. A contaminant identified in EMS-associated L-tryptophan preparations has been isolated and characterized, but its biologic effects and role as the etiologic agent in EMS remain to be established. Pathologic observations and experimental studies indicate that eosinophils, mononuclear inflammatory cells, and fibroblasts are potential effector cells, and interleukin-5 and transforming growth factor-beta are important mediators in the pathogenesis of the syndrome. Although few new cases of EMS occurred following the withdrawal of L-tryptophan, affected patients continue to manifest late sequelae of the disease, including dermal fibrotic conditions. This tragic outbreak of a newly recognized illness has focused interest on the role of chemical and environmental agents in the pathogenesis of various idiopathic illness characterized by tissue inflammation and fibrosis.
Varga
J
J
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Jimenez
S A
SA
Uitto
J
J
D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D004340:Drug Contamination; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D004804:Eosinophils / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D014364:Tryptophan / Q000009:adverse effects* / Q000737:chemistry
D014364:Tryptophan