An Investigation of the Cause of the Eosinophilia–Myalgia Syndrome Associated with Tryptophan Use

Belongia, Edward A.; Hedberg, Craig W.; Gleich, Gerald J.; White, Karen E.; Mayeno, Arthur N.; Loegering, David A.; Dunnette, Sandra L.; Pirie, Phyllis L.; MacDonald, Kristine L.; Osterholm, Michael T.

doi:10.1056/nejm199008093230601

Cited by 341 publications

(78 citation statements)

References 15 publications

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“…This question arose when tryptophan became unavailable in various countries after tryptophan from a single manufacturer that contained a toxic trace impurity caused a number of deaths and disabilities due to a disorder that came to be called eosinophilia myalgia syndrome. 95 Krahn and colleagues 55 compared the effect of 100 g and 25 g tryptophandeficient amino acid mixtures. They confirmed the finding of my colleagues and I 89 that the 25 g mixture caused a much smaller decline in tryptophan availability and reported that the 8 participants who received both mixtures could not distinguish between them.…”

mentioning

confidence: 99%

Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

Young

2013

J Psychiatry Neurosci

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mentioning

confidence: 99%

Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

Young

2013

J Psychiatry Neurosci

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“…Examples include drug-induced lupus (1), toxic oil syndrome (2,3), and contaminated L-tryptophan ingestion (4,5). Numerous mechanisms, based on in vitro evidence and animal models, have been proposed to explain how xenobiotics may induce or accelerate autoimmunity.…”

mentioning

confidence: 99%

Environmentally induced autoimmune diseases: potential mechanisms.

Rao

Richardson

1999

Environ Health Perspect

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Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists.

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“…The eosinophilia-myalgia syndrome was linked with tryptophan use after a case-control investigation, but a second case-control study was necessary to pin point the brand and retail lot numbers of the tryptophan responsible. 16 This was subsequently confirmed by chemical analysis of the implicated tryptophan brand. Rapid epidemiological investigation thus led to early containment measures and prevented further public exposure to the causative agent.…”

Section: Discussionmentioning

confidence: 64%

Use of sequential case-control studies to investigate a community Salmonella outbreak in Wales

Llewellyn¹,

Evans²,

Palmer³

1998

Journal of Epidemiology & Community Health

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Study objective-To establish the source of a community outbreak of Salmonella typhimurium definitive type 124. Design-Two stage case-control study. Setting-Three districts in south east Wales. Subjects-Cases of salmonella food poisoning and community controls. Main results-An initial case-control study identified an association between illness and eating ham (odds ratio 4.50, 95% confidence intervals 1.10, 21.8) and also found a possible association between illness and food bought from delicatessen stores (odds ratio 5.03, 95% confidence intervals 1.01, 32.3). However, only after a second stage case-control study was a single common ham producer identified as the source (odds ratio 25.0, 95% confidence intervals 2.33, 1155). Conclusion-Sequentialcase-control studies are an important and underused tool in the investigation of community outbreaks.

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An Investigation of the Cause of the Eosinophilia–Myalgia Syndrome Associated with Tryptophan Use

Cited by 341 publications

References 15 publications

Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

Environmentally induced autoimmune diseases: potential mechanisms.

Use of sequential case-control studies to investigate a community Salmonella outbreak in Wales

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