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The Cause and Pathogenesis of the Eosinophilia-Myalgia Syndrome

John Varga, MD; Jouni Uitto, MD, PhD; and Sergio A. Jimenez, MD
[+] Article, Author, and Disclosure Information

Grant Support: By NIH grants AR-19616, AR-01817. and AR-41439.

Requests for Reprints: John Varga, MD, Division of Rheumatology Research, Bluemle Life Sciences Building, Room 509, 233 South 10th Street, Philadelphia, PA 19107.

Current Author Addresses: Dr. Varga: Department of Medicine, Division of Rheumatology Research, Room 522, Bluemle Life Sciences Building, 233 South 10th Street, Philadelphia, PA 19107.

Dr. Uitto: Department of Dermatology, Room 450, Bluemle Life Sciences Building, 233 South 10th Street, Philadelphia, PA 19107.

Dr. Jimenez: Department of Medicine, Division of Rheumatology Research Room 509, Bluemle Life Sciences Building, 233 South 10th Street, Philadelphia, PA 19107.

© 1992 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1992;116(2):140-147. doi:10.7326/0003-4819-116-2-140
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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.





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