伴侣动物食物不良反应的批判性评价话题 (4)：我们能否通...

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伴侣动物食物不良反应的批判性评价话题 (4)：我们能否通过体内或体外试验诊断犬和猫的食物不良反应？

Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests?

Ralf S. Mueller and Thierry Olivry

翻译：许晓鸥

Abstract

Background: The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals.

Results: We searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated.

Conclusions: Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

Keywords: Atopic, Canine, Feline, Food allergy, Gastroenteritis, In vitro, Serum test, IgE

摘要

背景：诊断犬和猫食物不良反应 (AFR) 的金标准目前是食物排除激发试验。但是，这些试验不方便，患者依从性可能较低。我们的目的是对文献进行系统性审查，以评价用于诊断小型动物 AFR 的体内和体外试验。

结果：我们在三个数据库（CAB 摘要、MEDLINE 和 Web of Science）中检索了 2016 年 9 月 16 日的相关参考文献。在 CAB 摘要、MEDLINE 和 Web of Science 数据库中检索到的 71 篇、544 篇和 41 篇文献中，我们选择了 22 篇报告数据可用于评价 AFR 试验的文献和摘要。评价了食物特异性 IgE 和 IgG 的血清试验、食物抗原皮内试验、淋巴细胞增殖试验、粪便食物特异性 IgE、贴片、胃镜和结肠镜试验。结论：血清食物特异性 IgE 和 IgG 检测显示重复性较低，在犬中，准确度差异较大。在猫中，检测食物特异性 IgE 的准确性较低。淋巴细胞增殖试验在 AFR 动物中更常见阳性和更准确，但由于其更难以进行，因此仍是目前的研究工具。所有其他报告的试验仅通过使用少量动物的个体研究进行评价。阴性贴片试验反应在犬中具有非常高的阴性可预测性，并且能够在选定患者中选择用于食物排除的成分。胃镜和结肠镜检查以及食物特异性粪便 IgE 或食物特异性血清 IgG 测定似乎不太有用。目前，识别小动物 AFRs 的最佳诊断方法仍然是日粮排查，随后进行激发试验。

关键词：特应性皮炎、犬、猫、食物过敏、胃肠炎、体外、血清试验、IgE

Background

背景

Elimination diets with subsequent provocation trials are uniformly recommended to diagnose adverse food reactions (AFRs) in dogs and cats. However, performing home-cooked elimination diets and monitoring of clinical changes during the diet and subsequent provocation tests are work-intensive and time consuming and pet and client compliance is variable. For owners, laboratory tests of blood, saliva, and hair from patients offer an easier way to achieve a diagnosis of AFRs.

食物排除与随后的激发试验被一致推荐用于诊断犬和猫的食物不良反应 (AFR) 。然而，在食物排除和随后的激发试验过程中进行家庭自制食物排除和监测临床变化的工作密集和耗时，以及宠物和主人的依从性是多变的。对于主人来说，对病例的血液、唾液和毛发进行实验室检测，为实现 AFRs 的诊断提供了一种更简单的方法。

Clinical scenario

临床案例

Consider the example of two patients: a six-month-old female intact Labrador retriever and a five-year-old female spayed Domestic Shorthair cat. Both animals exhibit pruritus that manifests by year-round scratching. The dog also suffers from flatulence and occasional episodes of vomiting. The cat has several patches of self- induced hair loss on the abdomen and flanks and an indolent ulcer on the left upper lip. You inform the owners of both patients that you suspect that all clinical signs might be caused by a reaction to a component of their pet’s diet and advise that an elimination diet is indicated for eight weeks to evaluate potential food involvement. The owners ask you if there is an easier way to identify the role of food antigens such as, for example, a blood test.

举个例子，有两个病人：一只六个月大的雌性拉布拉多犬和一只五岁大的雌性家养短毛猫。两种动物均表现为瘙痒，表现为常年搔抓。该犬还出现胃肠胀气，偶有呕吐发作。猫腹部和侧腹有几处自我损伤导致的脱毛斑，左上唇有一处无痛性溃疡。您告知两名患者的主人，您怀疑所有临床症状可能是对其宠物日粮成分的反应引起的，并建议进行8周的食物排除以评估潜在的食物相关性。主人会问你是否有更简单的方法来确定食物抗原的作用，例如，血液学试验。

Structured question

问题框架

Can we diagnose AFRs in dogs and cats with in vivo or in vitro tests?

我们能否通过体内或体外试验诊断犬和猫的 AFRs？

Search strategy

检索方法

We searched the Web of Science (Core Collection), MEDLINE and CAB Abstract databases on September 16, 2016 using the following string: (dog* or canine or cat* or feline) and (food* or diet*) and test* and (allerg* or hypersens* or adverse) not (human* or child* or adult*). We limited the search to journal articles published from 1980 to present; there were no language restrictions. Bibliographies from selected articles and proceedings of recent specialized veterinary dermatology and internal medicine conferences were also searched.

我们于 2016 年 9 月 16 日使用以下字符串检索了 Web of Science（核心集）、MEDLINE 和 CAB 摘要数据库：（犬 * 或canine或猫 * 或feline）and（食物 * 或饮食 *）and（过敏 allerg* 或感觉过敏 hypersens* 或不良）not（人 * 或儿童 * 或成人 *）。我们限制检索 1980 年至今发表的期刊论文；没有语言限制。还检索了选定文章的参考书目和最近专门的兽医皮肤病学和内科学会议的会议记录。

Identified evidence

确定证据

Our literature search identified 71, 544 and 41 articles in the CAB Abstract, MEDLINE and Web of Science (Core Collection) databases, respectively. Abstracts of relevant titles were screened and any potentially useful manuscript was downloaded and scrutinised in detail. The bibliography of these articles was examined further for additional pertinent citations. In addition, proceedings of recent veterinary dermatology or internal medicine conferences were evaluated.

我们的文献检索在 CAB 摘要、MEDLINE 和 Web of Science (Core Collection) 数据库中分别识别了 71、544 和 41 篇文章。筛选相关标题的摘要，下载任何可能有用的手稿，并详细审查。进一步检查这些文章的参考书目，以获得额外的相关引文。此外，对最近的兽医皮肤病学或内科学会议记录进行了评价。

Altogether, we selected 23 papers and one abstract from conference proceedings that re- ported results of various laboratory tests in dogs or cats where an AFR was definitely diagnosed or ruled-out. We excluded studies where the diagnosis of AFR was not confirmed or the results of the individual laboratory tests could not be attributed to a specific patient. The chosen publications were mostly case-control studies, and there were two case series and one each a single case report and a prospective cohort study . In all, there were twelve studies testing food- specific IgE in the serum of dogs and three in cats . Four studies also evaluated canine food-specific IgG . Lymphocyte proliferation tests were assessed in four studies in dogs  and one in cats . In dogs, intradermal testing and gastroscopic food testing were reported in six and three studies respectively. There were two studies for patch testing in dogs , and one study each for gastroscopic food testing in cats , colonoscopic testing in dogs , determination of canine fecal IgE and hair and saliva testing in dogs . Some studies evaluated several different tests in dogs and in cats . Studies were reported from 1991 to 2017 . All papers were in English except one, which was in German . The number of animals and type of test performed in each paper are listed in Table 1.

总之，我们从会议记录中选择了 23 篇论文和一篇摘要，报告了明确诊断或排除 AFR 的犬或猫的各种实验室检查结果。我们排除了未确诊 AFR 或个体实验室检查结果不能归因于特定患者的研究。所选出版物大多为病例对照研究，有 2 个病例系列和 1 个单个病例报告和 1 个前瞻性队列研究。总共有 12 项研究检测了犬血清中的食物特异性 IgE，3 项研究检测了猫血清中的。4 项研究还评价了犬食物特异性 IgG。在 4 项犬研究和 1 项猫研究中评估了淋巴细胞增殖试验。在犬中，分别有 6 项研究和 3 项研究报告了皮内试验和胃镜食物试验。在犬中进行了 2 项贴片试验研究，在猫中进行胃镜食物试验、在犬中进行结肠镜检查、测定犬粪便 IgE以及在犬中进行毛发和唾液试验。一些研究评价了犬和猫中的几种不同试验。1991 年至 2017 年报告的研究。除 1 例病例是在德国外，所有病例均为英文。表 1 列出了每篇论文中执行的动物数量和试验类型。

Evaluation of evidence

证据评估

Calculations of the accuracy, positive and negative predictabilities of the various tests for a positive food challenge in dogs and cats with naturally occurring AFRs are reported in Tables 2 and 3, respectively.

在表 2 和表 3 中分别报告了对自然发生 AFR 的犬和猫进行的各种阳性食物激发试验的准确性、阳性和阴性预测能力的证据计算评价。

These parameters could not be evaluated in nine of the selected studies, mainly because of the lack of performance of provocation tests with individual food items. One report only provided details of the individual positive, but not negative provocation trials—and this prevented the calculation of the tests’ accuracy. Some studies evaluated the tests only in laboratory dogs, and it is not clear if the pathophysiology of AFRs in sensitized laboratory animals mirrors that of the naturally-occurring dis- ease. In most studies using laboratory dogs, the tests were more accurate, presumably because the more controlled environment and food intake might have minimized the impact of other environmental factors that could be influencing the development of clinical signs. Some studies had only six or fewer of dogs or cats  with AFRs included. While most reports were of animals with cutaneous AFRs, dogs and cats with gastrointestinal disease were also included in some articles.

这些参数无法在所选的 9 项研究中进行评价，主要是因为缺乏对单个食物进行的激发试验。一份报告只提供了个别阳性激发试验的细节，而没有提供阴性激发试验的细节——这妨碍了试验准确性的计算。一些研究仅在实验犬中评价了试验，尚不清楚致敏实验动物中 AFRs 的病理生理学是否与自然发病的病理生理学相似。在大多数使用实验室犬的研究中，试验更准确，可能是因为更受控的环境和摄食量可能将可能影响临床体征发展的其他环境因素的影响降至最低。一些研究中仅有 6 只或更少的犬或猫包含 AFR。虽然大多数报告是关于患有皮肤 AFR 的动物，但在一些文章中也纳入了患有胃肠道疾病的犬和猫。

While testing for allergen-specific IgE is well established for environmental allergens in humans, dogs and cats, it is also offered for food allergens in many countries; this explains while most of our included studies evaluated serum food-specific IgE testing. Two studies showed a low repeatability of serum food-specific IgE and IgG testing when different aliquots of the same sample were evaluated in a blinded fashion, the authors then concluded that these tests were unsuitable for clinical use. One study found a high concentration of food-specific serum IgE in a large number of dogs that had environmental atopic dermatitis and that had signs that did not improve after being fed an elimination diet. Similar results were obtained in other studies in which dogs with AFRs were compared to apparently healthy dogs. When the serum test results for food-specific IgE were correlated with food provocation outcomes in dogs with AFRs, the tests’ accuracy and positive and negative predictabilities varied highly.

虽然针对人类、犬和猫中环境过敏原的过敏原特异性 IgE 检测已充分确立，但在许多国家也提供针对食物过敏原的检测；这解释了我们纳入的大多数研究评价了血清食物特异性 IgE 检测的原因。两项研究表明，当以盲态方式评价同一样本的不同等份试样时，血清食物特异性 IgE 和 IgG 检测的重复性较低，作者随后得出结论，这些检测不适合临床使用。一项研究发现，在大量患有环境性特应性皮炎且进行食物排除实验后体征未改善的犬中，存在高浓度的食物特异性血清 IgE。在其他研究中获得了相似的结果，其中将 AFRs 犬与表观健康犬进行了比较。当食物特异性 IgE 的血清检测结果与 AFRs 犬的食物激发结果相关时，检测的准确性和阳性和阴性预测能力差异很大。

Intradermal testing with food antigens in laboratory dogs sensitized to specific foods usually yielded concordant positive reactions. When allergic patients in clinical practice were tested, however, dogs with environmental, but non- food-induced atopic dermatitis also exhibited numerous positive reactions to food antigens, while dogs with AFRs often had no positive results.

对特定食物致敏的实验犬进行食物抗原皮内试验，通常会产生一致的阳性反应。然而，当对临床实践中的过敏患者进行检测时，环境但非食物诱导的特应性皮炎犬对食物抗原也表现出许多阳性反应，而 AFRs 犬通常无阳性结果。

With lymphocyte proliferation tests, the accuracy was generally higher, but this test is technically more difficult to conduct and blood specimens need to be processed very quickly after sampling, two reasons why this test is generally not offered by commercial laboratories.

淋巴细胞增殖试验的准确度普遍较高，但该试验在技术上较难进行，取样后需要非常快速地处理血液标本，这也是商业实验室一般不提供该试验的两个原因。

In the two studies assessing the usefulness of patch testing with food antigens, the accuracy and negative predictability of patch testing were satisfactory and excellent respectively (particularly for protein sources), but the positive predictability was low. As a result, this test cannot be used for the diagnosis of AFR but it could be useful as a tool to identify suitable ingredients for the elimination diet in selected dogs.

在评估食物抗原贴片试验有用性的两项研究中，贴片试验的准确性和阴性预测性分别令人满意和极好（特别是蛋白来源），但阳性预测性较低。因此，该试验不能用于 AFR 的诊断，但可作为工具用于确定选定犬中食物排除实验的适当成分。

Gastroscopic testing had an unsatisfactory accuracy in dogs and cats; the same was evaluated for fecal food-specific IgE and hair and saliva testing.

犬和猫的胃镜检查准确度不理想；粪便食物特异性IgE和毛发及唾液检查也是如此。

Conclusion and implication for practitioners

结论和对临床医生的启示

Patch testing with food ingredients might be useful in some selected dogs to choose the ingredients for an elimination diet. Currently, all other tests cannot be recommended for the clinical diagnosis of AFRs in dogs and cats. Although serum IgE testing for food-specific IgE is offered by many laboratories in many countries as a tool for the diagnosis of AFRs, it is not reliable in dogs and cats. At this time, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

食物成分的贴片试验可能对一些选定的犬选择食物排除的成分有用。目前，所有其他试验均不推荐用于犬和猫 AFRs 的临床诊断。尽管许多国家的许多实验室提供了食物特异性 IgE 的血清 IgE 检测作为诊断 AFRs 的工具，但其在犬和猫中并不可靠。此时，识别小动物 AFRs 的最佳诊断方法仍然是食物排除实验，随后进行激发试验。

南海

洋芋那个土豆

Vet武

曾医生

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