Eosinophilia-myalgia syndrome

ELISA Enzyme-linked immunosorbent assay EMS Eosinophilia-myalgia syndrome ENS Enteric nervous system EO Eosinophil... 

FDA recalls all OTC dietary supplements containing L-tryptophan because of a clear link to an outbreak of eosinophilia-myalgia syndrome (EMS). By 1990, more than 1,500 cases of EMS - 38 deaths are confirmed, with an estimated 3,000 to 10,000 unreported cases. 

The eosinophilia myalgia syndrome (EMS) is a complex systemic syndrome with inflammatory and autoimmune components that affects the skin, fascia. 

L-Tryptophan. Open label studies suggest that tryptophan, the amino acid precursor to serotonin, administered at 500-2000mg/day, may be effective for OCD. This has not been tested in controlled studies. Furthermore, the clinical utility of tryptophan snpplementation has been limited by the association of one batch of tryptophan with the eosinophilia myalgia syndrome. Therefore, we cannot recommend the rontine nse of tryptophan supplementation for OCD. 

Add tryptophan to a standard antidepressant (usually an SSRI). There is a danger that the serotonin syndrome may occur however and occasionally the eosinophilia myalgia syndrome. The symptoms that occur with increasing severity are restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death. 

Sullivan, E.A., Kamb, M.L., Jones, J.L., Meyer, P., Philen, R.M., Falk, H., and Sinks, T. (1996) The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 156 973-975. 

Hermoni M, Lerer B, Ebstein RP, et al Chronic lithium prevents reserpine-induced supersensitivity of adenylate cyclase. J Pharm Pharmacol 32 510-511, 1980 Hertzman PA, Blevins WL, Mayer J, et al Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan [see comments]. N Engl J Med 322 869-873, 1990... 

Limited evidence indicates that the amino acid precursor of 5-HT, l -tryptophan, may be useful, alone or in combination with other antimanic agents to enhance overall efficacy. Contaminants in the production of this agent led to several cases of the eosinophilia myalgia syndrome (EMS) and its removal from the market for several years. 

The reliability and consistency of commercial melatonin has been questioned (3). One group analysed three commercial melatonin formulations and identified analogues of the contaminant of L-tryptophan compounds implicated in an epidemic of eosinophilia-myalgia syndrome in the 1980s (27). There have been no reports of this condition associated with melatonin consumption, but food supplements are not required to comply with the same manufacturing and monitoring quality control standards as drugs. 

Mayeno AN, Lin F, Foote CS, Loegering DA, Ames MM, Hedberg CW, Gleich GJ. Characterization of Peak E , a novel amino acid associated with eosinophilia-myalgia syndrome. Science 1990 250 1707-1708. 

Hill RH Jr, Caudill SP, Philen RM, Bailey SL, Flanders WD, Driskell WJ, Kamb ML, Needham LL, Sampson EJ. Contaminants in L-tryptophan asso-ciatedwith eosinophilia-myalgia syndrome. Arch Environ Contam Toxicol 1993 25 134-142. 

Williamson, B. L. Tomlinson, A. I Mishra, P. K. Gleich, G. J. Naylor, S. 1998. Structural characterization of contaminants found in commercial preparations of melatonin similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem. Res. Toxicol., 11,234-240. 

Analysis of L-tryptophan for etiology of eosinophilia-myalgia syndrome, JAMA, 264 2620 (1990). 

Another case, much more serious and also more pertinent to the chemical process development area, occurred in 1989 when over 1600 people became ill with eosinophilia-myalgia syndrome (EMS) and 38 died, worldwide, after taking l-tryptophan (Trp) manufactured by one producer in Japan. Prior to the outbreak, this producer whose Trp met the >98.5% purity specification had decided to employ a new genetically modified strain of the established Bacillus amyloliquefaciens and also to halve the amount of activated charcoal used in the purification step. These changes cause the Trp product to become contaminated with several new impurities, principally I to III, all associated to some extent (using a crude animal model) with EMS.5... 

Tryptophan Amino acid Precursor of serotonin Eosinophilia-myalgia syndrome... 

The syndrome appears to be only part of a spectrum of adverse effects associated with tryptophan (15). There has been much discussion, but finally it appears that the links are causal, as consistent findings were found in multiple independently conducted studies and the incidence of eosinophilia-myalgia syndrome in the USA fell abruptly once tryptophan-containing products were recalled (16). 

Varga J, Uitto J, Jimenez SA. The cause and pathogenesis of the eosinophilia-myalgia syndrome. Ann Intern Med 1992 116(2) 140-7. 

Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996 46 81-8. 

Hypersensitivity reactions can occur due to the presence of contaminants or excipients in pharmaceutical dosage forms (e.g., outbreaks of eosinophilia-myalgia syndrome associated with oral tryptophan contaminants in various drugs). Another example is the anaphylactoid reactions to the surfactant Cremaophor EL, which is used in paclitaxel (Taxol). 

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