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A strategy for skin irritation testing 一种皮肤刺激试验策略
Pub Date : 2002-03-01 DOI: 10.1053/ajcd.2002.30471
Michael K. Robinson, Mary A. Perkins

Skin irritation safety testing and risk assessment for new products, and the ingredients they contain, is a critical requirement before market introduction. In the past, much of this skin testing required the use of experimental animals. However, new current best approaches for skin corrosion and skin irritation testing and risk assessment are being defined, obviating the need for animal test methods. Several in vitro skin corrosion test methods have been endorsed after successful validation and are gaining acceptance by regulatory authorities. In vitro test methods for acute, cumulative (repeat exposure), and chronic (prolonged exposure) skin irritation are under development. Though not yet validated, many are being used successfully for testing and risk assessment purposes as documented through an expanding literature. Likewise, a novel acute irritation patch test in human subjects is providing a valid and ethical alternative to animal testing for prediction of chemical skin irritation potential. An array of other human test methods also have been developed and used for the prediction of cumulative/chronic skin irritation and the general skin compatibility of finished products. The development of instrumental methods (e.g., transepidermal water loss, capacitance, and so on) has provided the means for analyzing various biophysical properties of human skin and changes in these properties caused by exposure to irritants. However, these methods do not directly measure skin inflammation. A recently introduced skin surface tape sampling procedure has been shown to detect changes in skin surface cytokine recovery that correlate with inflammatory skin changes associated with chemical irritant exposures or existing dermatitis. It holds promise for more objective quantification of skin irritation events, including subclinical (sensory) irritation, in the future.

对新产品及其所含成分进行皮肤刺激安全测试和风险评估是向市场推出前的一项关键要求。在过去,这种皮肤测试需要使用实验动物。然而,目前正在定义新的皮肤腐蚀和皮肤刺激测试和风险评估的最佳方法,从而消除了动物试验方法的需要。几种体外皮肤腐蚀试验方法在成功验证后得到认可,并正在获得监管机构的接受。急性、累积(重复暴露)和慢性(长时间暴露)皮肤刺激的体外试验方法正在开发中。虽然还没有被证实,但是许多已经被成功地用于测试和风险评估目的,通过不断扩大的文献记录。同样,在人类受试者中进行的一种新的急性刺激斑贴试验为预测化学皮肤刺激电位提供了一种有效和道德的替代动物试验。一系列其他人体试验方法也已被开发并用于预测累积/慢性皮肤刺激和成品的一般皮肤相容性。仪器方法的发展(例如,经皮失水、电容等)为分析人体皮肤的各种生物物理特性以及暴露于刺激物引起的这些特性的变化提供了手段。然而,这些方法并不能直接测量皮肤炎症。最近引入的皮肤表面胶带取样程序已被证明可以检测皮肤表面细胞因子恢复的变化,这些变化与化学刺激物暴露或现有皮炎相关的炎症性皮肤变化有关。它有望在未来更客观地量化皮肤刺激事件,包括亚临床(感觉)刺激。
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引用次数: 38
Allergic contact dermatitis from mercury antiseptics and derivatives: Study protocol of tolerance to intramuscular injections of thimerosal 汞防腐剂及其衍生物引起的过敏性接触性皮炎:对肌内注射硫柳汞的耐受性研究方案
Pub Date : 2002-03-01 DOI: 10.1053/ajcd.2002.29945
Mar[iacute]a Teresa Audicana, Daniel Mu[ntilde]oz, Mar[iacute]a Dolores del Pozo, Eduardo Fern[aacute]ndez, Gabriel Gastaminza, Luiz Fern[aacute]ndez de Corres

Background: Mercury derivatives are frequent contact allergens and their cross-reactivity is not constant. Thimerosal is an organic mercurial used as an antiseptic and as a preservative in most vaccines. Objective: To evaluate cross-reactivity, exposure factors, and tolerance to vaccines containing thimerosal in patients sensitized to mercury derivatives. Methods: Design: Observational study (cross-sectional); Patients: 125 patients were recruited for the study, 72 women and girls and 53 boys and men, average age 18.7 years old, range 3 to 65, with positive patch tests to mercury derivatives and/or thimerosal; Interventions: All patients were studied by means of enquiry, patch tests, intradermal tests, and intramuscular challenge with thimerosal. Results: A sensitization to thimerosal was observed in 57 patients. Twenty-four of these 125 patients presented a positive intradermal reaction. Ammoniated mercury seems to be a good marker of mercury sensitization eliciting positive reaction in 78% of all patients and merbromin in 66%. In most cases, (100/125) cross-reactivity was found among mercury derivatives. The intramuscular injection of thimerosal induced a mild local reaction in only 5 patients (4% of the total, 9% of thimerosal positive reactions). Childhood vaccinations, merbromin used as an antiseptic, broken thermometers, and the use of drops were the main sources of exposure. Conclusions: The majority of the patients showed positive tests to both organic and inorganic mercury derivatives. Vaccination with thimerosal is relatively safe, even for individuals with delayed type hypersensitivity to this chemical, since more than 90% of allergic patients tolerated intramuscular challenge tests with thimerosal. A simplified protocol of patch tests to study mercury derivatives is proposed. It would be advisable to restrict the use of mercurial antiseptics and mercury thermometers.

背景:汞衍生物是常见的接触性过敏原,其交叉反应性不是恒定的。硫柳汞是一种有机汞,在大多数疫苗中用作防腐剂和防腐剂。目的:评价汞衍生物致敏患者对含硫柳汞疫苗的交叉反应性、暴露因素和耐受性。设计:观察性研究(横断面);患者:研究招募了125名患者,72名女性和女孩,53名男性和男孩,平均年龄18.7岁,年龄范围3至65岁,对汞衍生物和/或硫柳汞的斑贴试验呈阳性;干预措施:通过询问、贴片试验、皮内试验和肌内注射硫柳汞对所有患者进行研究。结果:57例患者出现硫柳汞致敏。125例患者中有24例出现皮内阳性反应。氨化汞似乎是一个很好的汞致敏标志物,在所有患者中引起78%的阳性反应,在所有患者中引起66%的阳性反应。在大多数情况下,汞衍生物之间存在(100/125)交叉反应性。肌注硫柳汞仅在5例患者中引起轻度局部反应(占总数的4%,9%的硫柳汞阳性反应)。儿童接种疫苗、作为防腐剂使用的汞溴、破损的温度计和使用滴剂是主要的接触源。结论:大多数患者对有机和无机汞衍生物的检测均呈阳性。硫柳汞疫苗接种是相对安全的,即使对这种化学物质有延迟型超敏反应的个体也是如此,因为90%以上的过敏患者耐受用硫柳汞进行肌肉注射试验。提出了一种简化的斑贴试验方案来研究汞衍生物。建议限制使用含汞防腐剂和汞温度计。
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引用次数: 54
Patch testing over tattoos 纹身贴片测试
Pub Date : 2002-03-01 DOI: 10.1053/ajcd.2002.29952
Joseph F. Fowler, M.Kathleen McTigue

Background: There is little, if any, literature regarding placing and reading of patch-tests on tattooed skin. Method: A patient whose entire back was covered with multiple tattoos was patch-tested. Results: Multiple positive patch-tests were seen with no apparent reduction in intensity related to tattooed skin. Conclusion: If necessary, patch-tests can be placed and read on tattooed skin

背景:关于在纹身皮肤上放置和阅读补丁测试的文献很少,如果有的话。方法:对全背多处文身的患者进行斑贴试验。结果:多次阳性贴片试验未见与纹身皮肤相关的强度明显降低。结论:如有必要,可以在纹身皮肤上放置贴片并读取
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引用次数: 4
Persistant hand eczema in a child 儿童持续性手部湿疹
Pub Date : 2002-03-01 DOI: 10.1053/ajcd.2002.29383
Mercedes Rodriguez-Serna, Jes[uacute]s Molinero, Isabel Febrer, Adolfo Aliaga
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引用次数: 8
Allergic contact dermatitis from phenylephrine in eyedrops 眼药水中的苯肾上腺素引起的过敏性接触性皮炎
Pub Date : 2002-03-01 DOI: 10.1053/ajcd.2002.30447
Stephan Michael Erdmann, Bernhardt Sachs, Hans F. Merk

Phenylephrine is widely used as an ophthalmic drug. However, there are only very few reports on allergic contact dermatitis induced by phenylephrine. In addition, little is known on cross reactivity patterns between the sympathomimetics phenylephrine, epinephrine and ephedrine which share a similar chemical structure. We report on a man who developed allergic contact dermatitis to Neosynerphin POS[reg ] eyedrops containing phenylephrine hydrochloride. Cross reactivity between phenylephrine, epinephrine and ephedrine was studied by patch testing. Patch tests were performed with the European standard, an ophthalmics and preservatives series, Neosynerphin POS[reg ] eyedrops, phenylephrine hydrochloride 10% aq., epinephrine and ephedrine (both 1.0 % aq.). Test sites were read after 48, 72 and 168 hours according to the recommendations of the ICDRG. Neosynerphin POS[reg ] and phenylephrine hydrochloride 10 % aq. gave positive reactions, whereas epinephrine and ephedrine tested negative. Although phenylephrine is an epinephrine analog delayed type hypersensitivity to phenylephrine did not result in cross reactivity with chemically related epinephrine and ephedrine.

苯肾上腺素是一种广泛使用的眼科药物。然而,关于苯肾上腺素引起的过敏性接触性皮炎的报道很少。此外,对具有相似化学结构的拟交感神经物质苯基肾上腺素、肾上腺素和麻黄碱之间的交叉反应模式知之甚少。我们报告一个人谁发展过敏性接触性皮炎的Neosynerphin POS[reg]眼药水含有盐酸苯肾上腺素。采用斑贴试验研究了苯肾上腺素、肾上腺素和麻黄碱的交叉反应性。用欧洲标准、眼药和防腐剂系列、Neosynerphin POS[reg]滴眼液、盐酸苯肾上腺素10% aq、肾上腺素和麻黄碱(均为1.0% aq)进行斑贴试验。根据ICDRG的建议,在48、72和168小时后读取测试点。新萘啡POS[reg]和盐酸苯肾上腺素10%阳性,而肾上腺素和麻黄碱阴性。虽然苯肾上腺素是一种肾上腺素类似物,但延迟型对苯肾上腺素的超敏反应不会导致与化学相关的肾上腺素和麻黄碱的交叉反应。
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引用次数: 15
Identification and quantification of para-phenylenediamine in a temporary black henna tattoo 临时黑色指甲花纹身中对苯二胺的鉴定和定量
Pub Date : 2002-03-01 DOI: 10.1053/ajcd.2002.30466
Ronald R. Brancaccio, Lance H. Brown, Young Tae Chang, Joshua P. Fogelman, Erick A. Mafong, David E. Cohen

Background: Temporary black henna tattoos are very popular as body adornment. Although contact allergy to natural henna is unusual, the inclusion of hair dye, p-phenylenediamine (PPD), increases the risk of contact sensitization. Objective: This study was performed to identify the presence and concentration of PPD in a black henna tattoo mixture to which our patient developed contact allergy. Methods: The presence of PPD in a black henna tattoo mixture, various samples of commercially available henna powders, and several hair dye products was qualitatively and quantitatively detected using high performance liquid chromatography (HPLC). Results: This study demonstrated that PPD was present in the black henna tattoo mixture at a concentration of 15.7%, which is significantly higher than commercial hair dye preparations. Conclusion: The presence of PPD in black henna tattoo mixtures in high concentration poses a health hazard and a risk of allergic contact sensitization with potential long-term consequences.

背景:临时黑色指甲花纹身是非常流行的身体装饰。虽然对天然指甲花的接触性过敏并不常见,但含有染发剂对苯二胺(PPD)会增加接触致敏的风险。目的:本研究的目的是确定PPD的存在和浓度在黑色指甲花纹身混合物,我们的病人发展接触性过敏。方法:采用高效液相色谱法(HPLC)对黑色指甲花纹身混合物、市售的各种指甲花粉样品和几种染发剂产品中PPD的存在进行定性和定量检测。结果:本研究表明,黑色指甲花纹身混合物中PPD的浓度为15.7%,明显高于市售染发剂制剂。结论:黑色指甲花纹身混合物中PPD的高浓度存在存在健康危害和过敏接触致敏风险,并具有潜在的长期后果。
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引用次数: 162
Cocamidopropyl betaine allergy 椰油酰胺丙基甜菜碱过敏
Pub Date : 2001-12-01 DOI: 10.1053/ajcd.2001.29549
Christen M. Mowad

Cocamidopropyl betaine (CAPB) is a surfactant, and reports of allergic contact dermatitis to this chemical have been reported in the literature. Although most commonly found in rinse-off products, the chemical nonetheless has been shown to induce allergy. The actual component responsible for allergic reaction may be the final compound itself, CAPB, or one of the substances used in its synthesis that may be present as an impurity. Allergy to CAPB is most commonly seen in a head and neck distribution, although other patterns have been identified.

椰油酰胺丙基甜菜碱(CAPB)是一种表面活性剂,有文献报道这种化学物质引起的过敏性接触性皮炎。尽管这种化学物质最常见于冲洗产品中,但已被证明会引起过敏。导致过敏反应的实际成分可能是最终化合物本身,CAPB或合成过程中使用的一种可能作为杂质存在的物质。对CAPB过敏最常见于头部和颈部分布,尽管已经确定了其他模式。
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引用次数: 20
Associated positive patch test reactions to standard contact allergens 贴片试验对标准接触性过敏原的阳性反应
Pub Date : 2001-12-01 DOI: 10.1053/ajcd.2001.26669
Jochen Brasch, Wolfgang Uter, Johannes Geier, Axel Schnuch, the German Contact Dermatitis Research Group and the Information Network of Departments of Dermatology in Germany*

Background: Patch testing with a standard allergen series often yields positive reactions to more than 1 allergen in a patient. Objective: To identify all significantly associated pairs of positive reactions and to assess their relation to the strength of the reactions and to the irritative potential of the allergens. Methods: Based on the filed data of 57,822 patients, associations between positive reactions to 2 different allergens were quantified with odds ratios. Statistical methods included Fisher's exact test, the Bonferroni adjustment to account for the effect of multiple testing, and the Spearman rank correlation. Results: Out of the 32,779 patients with complete readings of 24 standard allergens, 7,501 had shown more than 1 positive reaction. Statistically significant associations were detected for 166 out of the 276 possible different combinations of 2 distinct positive reactions, including combinations that had not been identified before. Patients with a strong reaction or a positive reaction to an allergen with a high irritative potential tended to have additional positive reactions to further allergens more often than others, but the number of significant associations was not dependent on these parameters. Conclusion: There are more significant associations that have to be taken into account for patch testing than has been known so far. Although irritation can favor a higher number of positive reactions, significant associations of positive reactions to distinct allergens are probably caused by other mechanisms that require further analyses.

背景:对患者进行标准过敏原系列的斑贴试验通常对1种以上的过敏原产生阳性反应。目的:确定所有显著相关的阳性反应对,并评估其与反应强度和过敏原刺激潜力的关系。方法:根据57,822例患者的现场资料,采用优势比量化2种不同过敏原阳性反应的相关性。统计方法包括Fisher精确检验、Bonferroni调整(用于解释多重检验的影响)和Spearman秩相关。结果:在32779例24种标准过敏原完整读数的患者中,7501例出现1种以上阳性反应。在276种可能的两种不同阳性反应组合中,有166种被检测出具有统计学意义的关联,包括之前未被识别的组合。对具有高刺激潜力的过敏原有强烈反应或阳性反应的患者往往比其他人更容易对其他过敏原产生额外的阳性反应,但显著关联的数量并不取决于这些参数。结论:有更多的重要的关联,必须考虑到补丁测试比已知的到目前为止。虽然刺激可以促进更多的积极反应,但对不同过敏原的积极反应的显著关联可能是由其他机制引起的,需要进一步分析。
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引用次数: 40
Combined contact and photocontact allergic dermatitis to etofenamate in flogoprofen gel 氟戈洛芬凝胶中乙托非甲酸酯的联合接触性和光接触性过敏性皮炎
Pub Date : 2001-12-01 DOI: 10.1053/ajcd.2001.23013
Javier S[aacute]nchez-P[eacute]rez, Tatiana Sanz S[aacute]nchez, Amaro Garc[iacute]a-D[iacute]ez

We report a case of combined contact and photocontact allergic dermatitis to etofenamate in Flogoprofen gel (Chiesi Wasserman, Barcelona, Spain). Patch test results were positive at the nonirradiated site, but there was a stronger reaction at the irradiated site with etofenamate 0.05% in petrolatum (pet.) at d2 and d4. The use frequent of topical agents containing etofenamate and sun exposure can result in a predisposition to contact photoallergy. Clinical findings caused by etofenamate are uncommon. Allergic contact dermatitis is the most common cutaneous reaction reported. In American studies observed, no reactions were observed to etofenamate in subjects with photosensitivity because it was not included in the series of antigens used in testing.

我们报告一例联合接触和光接触过敏性皮炎乙托芬酯氟洛芬凝胶(Chiesi Wasserman,巴塞罗那,西班牙)。未照射部位的斑贴试验结果为阳性,但在照射部位与0.05%凡士林(pet.)中的乙托非甲酸酯在d2和d4有较强的反应。经常使用含有乙托非甲酸酯的局部药物和暴露在阳光下会导致接触性光过敏的倾向。乙托非那酯引起的临床表现并不常见。过敏性接触性皮炎是最常见的皮肤反应。在美国观察到的研究中,没有观察到对乙托非甲酸酯有光敏反应的受试者,因为它不包括在测试中使用的抗原系列中。
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引用次数: 6
Contact dermatitis to topical drugs for glaucoma 接触性皮炎要局部用药治疗青光眼
Pub Date : 2001-12-01 DOI: 10.1053/ajcd.2001.25129
Mack R. Holdiness

A review of the literature has identified 10 agents causing contact dermatitis among topically administered drugs for glaucoma. These agents include [beta ]-blockers (timolol, befunolol, betaxolol, levobunolol, carteolol, metipranolol), a carbonic anhydrase inhibitor (dorzolamide), a parasympathomimetic (pilocarpine), and sympathomimetics (dipivefrin, apraclonidine). Patch testing has been documented in certain individuals as well as cross sensitization and reactivity. Systemic reactions to these topically applied medications have been briefly noted.

文献综述已经确定了10种药物引起接触性皮炎的局部给药青光眼。这些药物包括[β]受体阻滞剂(替马洛尔、贝福诺尔、倍他洛尔、左旋布诺尔、卡替洛尔、美特萘洛尔)、碳酸酐酶抑制剂(多唑胺)、拟副交感神经抑制剂(匹洛卡平)和拟交感神经药物(地哌维林、阿普lonidine)。补丁测试在某些个体以及交叉致敏和反应性中都有记录。对这些局部应用药物的全身反应已简要说明。
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引用次数: 41
期刊
American Journal of Contact Dermatitis
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