Document Detail


The cause and pathogenesis of the eosinophilia-myalgia syndrome.
MedLine Citation:
PMID:  1727618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To review recent advances in the understanding of the cause and pathogenesis of the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan. DATA SOURCES: Studies published from 1989 to 1991 were identified using a MEDLINE literature search. Additional references were selected from the bibliographies of identified articles. DATA SYNTHESIS: The eosinophilia-myalgia syndrome was epidemiologically associated with ingestion of L-tryptophan-containing preparations. Analysis of case-associated lots of L-tryptophan has revealed several chemical impurities. One of these, labeled "peak E," is an unusual dimeric form of L-tryptophan (1,1'-ethylidenebis[tryptophan]), and its presence is associated with the eosinophilia-myalgia syndrome (P = 0.022). Evidence of abnormal metabolism of tryptophan has been found in some patients with the syndrome. Eosinophil activation and the release of major basic protein and other eosinophil-derived toxic proteins into the extracellular space is a striking feature in the eosinophilia-myalgia syndrome and implicates eosinophils or their products in the pathogenesis. Mononuclear cell activation and infiltration of various affected tissues as well as fibrosis of the integument and of the connective tissue components of blood vessels, nerves, and muscles are additional frequent findings. CONCLUSIONS: Current evidence suggests that the epidemic of the eosinophilia-myalgia syndrome was caused by contaminated L-tryptophan preparations originating from a single manufacturer. Peak E or other, as yet unidentified, contaminants may trigger activation of eosinophils and inflammatory cells and increase biosynthesis of connective tissue components, resulting in the clinical and pathologic manifestations of the eosinophilia-myalgia syndrome. Further studies of the interaction of eosinophils, inflammatory cells, and fibroblasts may increase the understanding of the pathogenesis of the eosinophilia-myalgia syndrome. The insights gained from the epidemic may be applicable to more common idiopathic diseases associated with eosinophilia and fibrosis.
Authors:
J Varga; J Uitto; S A Jimenez
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Annals of internal medicine     Volume:  116     ISSN:  0003-4819     ISO Abbreviation:  Ann. Intern. Med.     Publication Date:  1992 Jan 
Date Detail:
Created Date:  1992-01-21     Completed Date:  1992-01-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372351     Medline TA:  Ann Intern Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  140-7     Citation Subset:  AIM; IM    
Affiliation:
Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
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MeSH Terms
Descriptor/Qualifier:
Drug Contamination
Eosinophilia-Myalgia Syndrome / etiology*,  immunology
Eosinophils / physiology
Humans
Tryptophan / adverse effects,  metabolism
Grant Support
ID/Acronym/Agency:
AR-01817/AR/NIAMS NIH HHS; AR-19616/AR/NIAMS NIH HHS; AR-41439/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
73-22-3/Tryptophan
Comments/Corrections
Comment In:
Ann Intern Med. 1992 Aug 15;117(4):344-5   [PMID:  1463513 ]

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