Síndrome da eosinofilia-mialgia

A síndrome de eosinofilia-mialgia (SEM) é uma condição neurológica rara, às vezes fatal, ligada à ingestão do suplemento dietético L-triptofano.  O risco de desenvolver essa doença aumenta com doses maiores de triptofano e com o aumento da idade.  Algumas pesquisas sugerem que certos polimorfismos genéticos podem estar relacionados ao desenvolvimento de da doença.  A presença de eosinofilia é uma característica central, juntamente com mialgia invulgarmente grave (dor muscular). Mayeno AN, Gleich GJ (September 1994). "Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale". Trends in Biotechnology. 12 (9): 346–52. doi:10.1016/0167-7799(94)90035-3. PMID 7765187.

Lindgren CE, Walker LA, Bolton P (February 1991). "L-tryptophan induced eosinophilia-myalgia syndrome". Journal of the Royal Society of Health. 111 (1): 29–30. doi:10.1177/146642409111100111. PMID 2005606. S2CID 31841865.

Mayeno AN, Gleich GJ (September 1994). "Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale". Trends in Biotechnology. 12 (9): 346–52. doi:10.1016/0167-7799(94)90035-3. PMID 7765187.

Okada S, Kamb ML, Pandey JP, Philen RM, Love LA, Miller FW (October 2009). "Immunogenetic risk and protective factors for the development of L-tryptophan-associated eosinophilia-myalgia syndrome and associated symptoms". Arthritis and Rheumatism. 61 (10): 1305–11. doi:10.1002/art.24460. PMC 2761987. PMID 19790128.

Milburn DS, Myers CW (November 1991). "Tryptophan toxicity: a pharmacoepidemiologic review of eosinophilia-myalgia syndrome". Annals of Pharmacotherapy. 25 (11): 1259–62. doi:10.1177/106002809102501116. PMID 1763543. S2CID 19913151.

Spitzer WO, Haggerty JL, Berkson L, Davis W, Palmer W, Tamblyn R, et al. (October 1996). "Analysis of Centers for Disease Control and Prevention criteria for the eosinophilia-myalgia syndrome in a geographically defined population". The Journal of Rheumatology. Supplement. 46: 73–9, discussion 79–80. PMID 8895183.

Blackburn WD (June 1997). "Eosinophilia myalgia syndrome". Seminars in Arthritis and Rheumatism. 26 (6): 788–93. doi:10.1016/S0049-0172(97)80022-4. PMID 9213377. A doença é objeto de atenção predominante por parte da reumatologia, e seu CID-10 é M35.8.

Sinais e sintomas A fase inicial aguda da doença, que dura de três a seis meses, apresenta problemas respiratórios e musculares, incluindo dor e espasmo, mas que também podem ser intensos. Fraqueza muscular não é uma característica desta fase, mas algumas pessoas experimentam rigidez muscular. Características adicionais podem incluir tosse, febre, fadiga, dor nas articulações, edema e dormência ou formigamento, geralmente nos membros, mãos e pés. A fase crônica segue a fase aguda. A fascite eosinofílica pode se desenvolver, principalmente nos membros. Sinais do sistema nervoso central podem aparecer, incluindo dormência, sensação aumentada, fraqueza muscular e, às vezes, disfunção cardíaca ou digestiva. A fadiga está presente em algum grau, enquanto a dor muscular (que pode ser extremamente intensa) e a dispnéia continuam nessa fase.

Causas Estudos epidemiológicos subsequentes sugeriram que a doença estava ligada a lotes específicos de L-triptofano fornecidos por um único grande fabricante japonês, Showa Denko.  Eventualmente, ficou claro que lotes recentes de L-triptofano da Showa Denko foram contaminados por traços de impurezas, que posteriormente foram considerados responsáveis ​​pelo surto da doença de 1989. O L-triptofano foi produzido por uma bactéria cultivada em cubas abertas em uma fábrica de fertilizantes Showa Denko.  Embora um total de 63 vestígios de contaminantes tenha sido identificados, apenas seis deles puderam ser associados a doença O composto EBT ("Peak E") foi o único contaminante identificável pela análise inicial, mas análises posteriores revelaram PAA , também conhecido como "UV-5") e peak 200. Mayeno AN, Gleich GJ (September 1994). "Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale". Trends in Biotechnology. 12 (9): 346–52. doi:10.1016/0167-7799(94)90035-3. PMID 7765187.

"Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan". FU. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. 2001-02-01. Archived from the original on 2005-02-25. Retrieved 2012-02-08.

Spitzer WO, Haggerty JL, Berkson L, Davis W, Palmer W, Tamblyn R, et al. (October 1996). "Analysis of Centers for Disease Control and Prevention criteria for the eosinophilia-myalgia syndrome in a geographically defined population". The Journal of Rheumatology. Supplement. 46: 73–9, discussion 79–80. PMID 8895183.

Mayeno AN, Lin F, Foote CS, Loegering DA, Ames MM, Hedberg CW, Gleich GJ (December 1990). "Characterization of "peak E," a novel amino acid associated with eosinophilia-myalgia syndrome". Science. 250 (4988): 1707–8. Bibcode:1990Sci...250.1707M. doi:10.1126/science.2270484. PMID 2270484.

Ito J, Hosaki Y, Torigoe Y, Sakimoto K (January 1992). "Identification of substances formed by decomposition of peak E substance in tryptophan". Food and Chemical Toxicology. 30 (1): 71–81. doi:10.1016/0278-6915(92)90139-C. PMID 1544609.

Hill RH, Caudill SP, Philen RM, Bailey SL, Flanders WD, Driskell WJ, et al. (July 1993). "Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome". Archives of Environmental Contamination and Toxicology. 25 (1): 134–42. doi:10.1007/bf00230724. PMID 8346973. S2CID 10182128.

Williamson BL, Johnson KL, Tomlinson AJ, Gleich GJ, Naylor S (October 1998). "On-line HPLC-tandem mass spectrometry structural characterization of case-associated contaminants of L-tryptophan implicated with the onset of eosinophilia myalgia syndrome". Toxicology Letters. 99 (2): 139–50. doi:10.1016/S0378-4274(98)00223-9. PMID 9817085.

Allen JA, Varga J (1 January 2014). "Eosinophilia–Myalgia Syndrome". Encyclopedia of Toxicology (Third Edition). Academic Press: 419–425. doi:10.1016/b978-0-12-386454-3.00018-x. ISBN 9780123864550.

Klarskov K, Gagnon H, Boudreault PL, Normandin C, Plancq B, Marsault E, et al. (January 2018). "Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome". Toxicology Letters. 282: 71–80. doi:10.1016/j.toxlet.2017.10.012. PMID 29037509.

Smith MJ, Garrett RH (November 2005). "A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation". Inflammation Research. 54 (11): 435–50. doi:10.1007/s00011-005-1380-7. PMID 16307217. S2CID 7785345.

Fernstrom JD (December 2012). "Effects and side effects associated with the non-nutritional use of tryptophan by humans". The Journal of Nutrition. 142 (12): 2236S–2244S. doi:10.3945/jn.111.157065. PMID 23077193. — Important: While this article may appear to be a normal peer-reviewed scientific publication at first glance, it is in fact actually a paid supplement (sponsored content, which is a form of native advertising) that did not go through the normal peer review process (or even the normal editorial process) for The Journal of Nutrition. It is legally required to be marked as a paid advertisement (a fact that was buried in a long footnote on the first page of the article rather than being clearly highlighted anywhere). Its sole author also disclosed a major conflict of interest due to them being "an occasional scientific advisor to the Ajinomoto Company" (the Ajinomoto Company specializes in producing animo acids, including tryptophan), and was sponsored by the International Council on Amino Acid Science (ICAAS), a non-profit association established for/by amino acids producers and users with a membership consisting exclusively of corporations with major financial conflicts of interest in the area, at least half of which are corporations which actually currently manufacture tryptophan (such as and including the Ajinomoto Company). This reference should not be considered a reliable source for anything beyond the sole claim it is used to support ("critics of this theory have argued that this hypothesis fails to explain the near-absent reports of EMS prior to and following the EMS outbreak"), and it is only used as the supporting reference for that claim in the first place because no higher-quality alternative to it currently exists.

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Dois dos "peaks" (substâncias, como o Peak E Peak 200) não associados inicialmente com a doença foram posteriormente determinados como sendo ácido 3a-hidroxi-1,2,3,3a,8,8a-hexahidropirrolo-[2,3-b]-indol-2-carboxílico (pico C) e 2-(2-hidroxi indolina)-triptofano (pico FF). Estes foram caracterizados usando LC-MS de massa precisa, LC-MS/MS (Cromatografia líquida-espectrometria de massa ) e espectrometria de massa de vários estágios (MS n).