Varga J, Uitto J, Jimenez S A
Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Ann Intern Med. 1992 Jan 15;116(2):140-7. doi: 10.7326/0003-4819-116-2-140.
To review recent advances in the understanding of the cause and pathogenesis of the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan.
Studies published from 1989 to 1991 were identified using a MEDLINE literature search. Additional references were selected from the bibliographies of identified articles.
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.
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.
综述与摄入L-色氨酸相关的嗜酸性粒细胞增多性肌痛综合征病因及发病机制的最新研究进展。
通过MEDLINE文献检索确定1989年至1991年发表的研究。从已确定文章的参考文献中选取其他参考文献。
嗜酸性粒细胞增多性肌痛综合征在流行病学上与摄入含L-色氨酸制剂相关。对与病例相关的L-色氨酸批次分析发现了几种化学杂质。其中一种标记为“峰E”，是L-色氨酸的一种不寻常二聚体形式（1,1'-亚乙基双[色氨酸]），其存在与嗜酸性粒细胞增多性肌痛综合征相关（P = 0.022）。在一些该综合征患者中发现了色氨酸代谢异常的证据。嗜酸性粒细胞活化以及主要碱性蛋白和其他嗜酸性粒细胞衍生的毒性蛋白释放到细胞外空间是嗜酸性粒细胞增多性肌痛综合征的一个显著特征，提示嗜酸性粒细胞或其产物参与发病机制。单核细胞活化以及各种受累组织的浸润，以及皮肤、血管、神经和肌肉结缔组织成分的纤维化是另外常见的发现。
目前证据表明，嗜酸性粒细胞增多性肌痛综合征的流行是由源自单一制造商的受污染L-色氨酸制剂引起的。峰E或其他尚未确定的污染物可能触发嗜酸性粒细胞和炎症细胞的活化，并增加结缔组织成分的生物合成，导致嗜酸性粒细胞增多性肌痛综合征的临床和病理表现。对嗜酸性粒细胞、炎症细胞和成纤维细胞相互作用的进一步研究可能会增加对嗜酸性粒细胞增多性肌痛综合征发病机制的理解。从该流行病中获得的见解可能适用于与嗜酸性粒细胞增多和纤维化相关的更常见特发性疾病。
