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工作场所中的乳胶过敏

Latex allergy in the workplace.

作者信息

Toraason M, Sussman G, Biagini R, Meade J, Beezhold D, Germolec D

机构信息

National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226, USA.

出版信息

Toxicol Sci. 2000 Nov;58(1):5-14. doi: 10.1093/toxsci/58.1.5.

Abstract

While less than 1% of the general population is sensitized to latex, the U.S. Occupational Safety and Health Administration estimates that 8-12% of health-care workers are sensitized. The major source of workplace exposure is powdered natural rubber latex (NRL) gloves. NRL is harvested from HEVEA: brasiliensis trees and ammoniated to prevent coagulation resulting in the hydrolysis of the latex proteins. Prior to use in manufacturing, the latex is formulated by the addition of multiple chemicals. Thus, human exposure is to a mixture of residual chemicals and hydrolyzed latex peptides. Clinical manifestations include irritant contact dermatitis, allergic contact dermatitis (type IV), and type I immediate hypersensitivity response. Type I (IgE-mediated) NRL allergy includes contact urticaria, systemic urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis. Taking an accurate history, including questions on atopic status, food allergy, and possible reactions to latex devices makes diagnosis of type-I latex allergy possible. To confirm a diagnosis, either in vivo skin prick testing (SPT) or in vitro assays for latex-specific IgE are performed. While the SPT is regarded as a primary confirmatory test for IgE-mediated disease, the absence of a U.S. Food and Drug Administration-licensed HEVEA: brasiliensis latex extract has restricted its use in diagnosis. Serological tests have, therefore, become critically important as alternative diagnostic tests. Three manufacturers currently have FDA clearance for in vitro tests, to detect NRL-specific IgE. The commercially available assays may disagree on the antibody status of an individual serum, which may be due to the assay's detecting anti-NRL IgEs to different allergenic NRL proteins. Sensitized individuals produce specific IgE antibody to at least 10 potent HEVEA: allergens, Hev b 1-Hev b 10, each of which differs in its structure, size, and net charge. The relative content and ratios of Hevs in the final allergen preparation most probably could effect diagnostic accuracy. The Hev proteins have been cloned and expressed as recombinant proteins. Sequencing demonstrates both unique epitopes and sequences commonly found in other plant proteins. Sequence homology helps to explain the cross reactivity to a variety of foods experienced by latex allergic individuals. The development of recombinant allergens provides reagents that should improve the diagnostic accuracy of tests for latex allergy. Although clinical and exposure data have been gathered on the factors affecting response in latex-allergic individuals, less is known regarding the development of sensitization. Coupled with in vitro dermal penetration studies, murine models have been established to investigate the route of exposure in the development of latex sensitization. Time-course and dose-response studies have shown subcutaneous, intratracheal, or topical administrations of non-ammoniated latex proteins to induce IgE production. Both in vitro penetration and in vivo studies highlight the importance of skin condition in the development of latex allergy, with enhanced penetration and earlier onset of IgE production seen with experimentally abraded skin. The diagnosis of latex allergy is complicated by these variables, which in turn hinder the development of intervention strategies. Further epidemiological assessment is needed to more explicitly define the scope, trends, and demographics of latex allergy. Diagnostic accuracy can be improved through greater knowledge of proteins involved in the development of latex allergy, and better documentation of the presently available diagnostic tests. In vivo and in vitro models can elucidate mechanisms of sensitization and provide an understanding of the role of the exposure route in latex allergy-associated diseases. Together, these efforts can lead to intervention strategies for reducing latex allergy in the workplace.

摘要

虽然普通人群中对乳胶敏感的比例不到1%,但美国职业安全与健康管理局估计,8% - 12%的医护人员对乳胶敏感。工作场所接触的主要来源是含粉天然橡胶乳胶(NRL)手套。NRL是从巴西橡胶树中采集的,并经过氨化处理以防止凝固,从而导致乳胶蛋白水解。在用于制造之前,乳胶会添加多种化学物质进行配制。因此,人体接触的是残留化学物质和水解乳胶肽的混合物。临床表现包括刺激性接触性皮炎、过敏性接触性皮炎(IV型)和I型速发型超敏反应。I型(IgE介导)NRL过敏包括接触性荨麻疹、全身性荨麻疹、血管性水肿、鼻炎、结膜炎、支气管痉挛和过敏反应。准确了解病史,包括询问特应性状态、食物过敏以及对乳胶制品可能的反应,有助于诊断I型乳胶过敏。为了确诊,可进行体内皮肤点刺试验(SPT)或针对乳胶特异性IgE的体外检测。虽然SPT被视为IgE介导疾病的主要确诊试验,但美国食品药品监督管理局未批准巴西橡胶树乳胶提取物用于诊断,这限制了其在诊断中的应用。因此,血清学检测作为替代诊断试验变得至关重要。目前有三家制造商的体外检测产品获得了美国食品药品监督管理局的批准,用于检测NRL特异性IgE。市售检测方法对个体血清的抗体状态可能存在分歧,这可能是由于检测方法针对不同的致敏NRL蛋白检测抗NRL IgE。致敏个体产生针对至少10种巴西橡胶树主要过敏原(Hev b 1 - Hev b 10)的特异性IgE抗体,每种过敏原在结构、大小和净电荷方面都有所不同。最终过敏原制剂中Hevs的相对含量和比例很可能会影响诊断准确性。Hev蛋白已被克隆并表达为重组蛋白。测序显示既有独特的表位,也有其他植物蛋白中常见的序列。序列同源性有助于解释乳胶过敏个体对多种食物产生交叉反应的现象。重组过敏原的开发提供了试剂,有望提高乳胶过敏检测的诊断准确性。尽管已经收集了关于影响乳胶过敏个体反应的因素的临床和接触数据,但对于致敏的发展了解较少。结合体外皮肤渗透研究,已建立小鼠模型来研究乳胶致敏发展过程中的接触途径。时间进程和剂量反应研究表明,皮下、气管内或局部给予非氨化乳胶蛋白可诱导IgE产生。体外渗透和体内研究均强调了皮肤状况在乳胶过敏发展中的重要性,实验性磨损皮肤会增强渗透并使IgE产生提前出现。这些变量使乳胶过敏的诊断变得复杂,进而阻碍了干预策略的制定。需要进一步的流行病学评估,以更明确地界定乳胶过敏的范围、趋势和人群特征。通过更深入了解参与乳胶过敏发展的蛋白质,以及更好地记录现有诊断检测方法,可以提高诊断准确性。体内和体外模型可以阐明致敏机制,并有助于理解接触途径在乳胶过敏相关疾病中的作用。综合这些努力可以制定出减少工作场所乳胶过敏的干预策略。

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