伴侣动物食物不良反应的批判性评价话题(9):食物过敏的犬和猫在食 ...

王帆

Critically appraised topic on adverse food reactions of companion animals (9): time to flare of cutaneous signs after a dietary challenge in dogs and cats with food allergies

伴侣动物食物不良反应的批判性评价话题(9):食物过敏的犬和猫在食物激发后皮肤症状爆发的时间

Thierry Olivry and Ralf S. Mueller

 

翻译：王帆

 

Abstract

Background: At this time, elimination diets followed by oral food challenges (OFCs) represent the “gold standard” for diagnosing skin-manifesting food allergies (FA) in dogs and cats. Regrettably, there is no clear consensus on how long one should wait for clinical signs to flare after an OFC before diagnosing or ruling-out a FA in a dog or a cat.

Results: We searched two databases on October 23, 2019 to look for specific information on the time for a flare of clinical signs to occur during OFCs after elimination diets in dogs and cats with skin-manifesting FAs. Altogether, we reviewed the study results of nine papers that included 234 dogs and four articles containing data from 83 cats. As multiple OFCs could be done in the same patient and not all animals included were subjected to an OFC, we were able to compile 315 and 72 times to flare (TTF) after an OFC in dogs and cats, respectively. When regrouping all cases together, about 9% of dogs and 27% of cats exhibited a flare of clinical signs in the first day after an OFC; 21% of dogs and 29% of cats had such relapse by the end of the second day. The time needed for 50 and 90% of dogs to exhibit a deterioration of clinical signs (TTF50 and TTF90) was 5 and 14, respectively; in cats, these times were 4 and 7 days, respectively. By 14 days after an OFC, nearly all food-allergic patients from both species had had a relapse of clinical signs. These results are limited by the likely under-reporting of flares that occur on the first day immediately following an OFC, the time in which IgE-mediated acute allergic reactions typically develop.

Conclusion: Veterinary clinicians performing an OFC need to wait for 14 and 7 days for more than 90% of dogs and cats with a skin-manifesting FA to have a flare of clinical signs, respectively.

Keywords: Food allergy, Oral food challenge, Oral provocation, Relapse

摘要

背景:目前，食物排查后食物激发(OFCs)是诊断犬和猫皮肤性食物过敏(FA)的“金标准”。遗憾的是，在诊断或排除犬或猫的FA之前，人们应该等待多长时间，直到有OFC的临床症状发作，目前还没有明确的共识。

结果:我们于2019年10月23日检索了两个数据库，以寻找关于在食物排查后出现皮肤FAs的犬和猫在OFCs期间出现大量临床症状的具体信息。我们总共回顾了包括234只犬的9篇论文和包含83只猫数据的4篇文章的研究结果。由于可以在同一患病动物中进行多个OFC，而并非所有纳入的动物都经历OFC，我们能够分别在犬和猫的OFC后编制315次和72次的TTF。当将所有病例重新组合在一起时，约9%的犬和27%的猫在OFC后的第一天表现出一些临床症状;21%的犬和29%的猫在第二天结束时复发。50%和90%的犬出现临床症状(TTF50和TTF90)恶化所需的时间分别为5和14;在猫上，这些时间分别是4天和7天。在OFC后的14天，几乎所有来自两个物种的食物过敏患病动物的临床症状都复发了。这些结果受到OFC后第一天(IgE介导的急性过敏反应通常发生的时间)发生急性发作可能漏报的限制。

结论:兽医临床医生实施OFC需要等待14天和7天以上，分别超过90%的犬和猫的皮肤显示FA有一个急性发作的临床症状。
关键词:食物过敏，口服食物激发，口服激发，复发

 

Background

背景

Cutaneous adverse food reactions (CAFRs), which are likely to represent food allergies (FAs) of immunologic origin, have a reported median prevalence of between 20 and 30% of pruritic, allergic or atopic dogs and half that in cats. As, to date, we could not identify any published article reporting dogs and cats with non-immune CAFRs, we will use the term FA thereafter. In the canine and feline species, FAs exhibit a wide range of manifestations that are limited to the skin or the gut or that affect both organs (reviewed in. As FAs are not diagnosed reliably using laboratory procedures or in vivo tests, clinicians are left recommending the performance of lengthy elimination diets that involve the feeding of previously-uneaten ingredients or diets with sufficiently hydrolyzed protein sources. By 8 weeks after starting such an elimination diet, the clinical signs of FA abate in over 90% of dogs and cats with FAs. After documenting a marked improvement of clinical signs or a return to normalcy, ultimately confirming the diagnosis of FA will need the elicitation of a clinical flare after feeding the original diet, often followed by a subsequent abatement of signs with a further feeding of the elimination diet. A provocation test with single ingredients can be performed subsequently to identify those responsible for the allergic reaction. At this time, however, there is no clear consensus on how long veterinarians should wait before deciding that, because of a lack of recurrence of signs, a patient could be deemed non-allergic to the newly-fed item. Finding the shortest duration of time needed to rule-out an allergy to a (full) diet or its ingredients is of importance to help increase the owner’s compliance with this notoriously lengthy process, especially when performing sequential challenges to individual food components.

皮肤不良食物反应(CAFR)很可能代表免疫来源的食物过敏(FA)，据报道，瘙痒、过敏或特异反应的犬的平均患病率在20 - 30%之间，猫的患病率为一半。因为，到目前为止，我们还没有发现任何发表的文章报道猫犬患有非免疫CAFR，我们将在以后使用FA这个术语。在犬和猫中，FA表现范围广泛，局限于皮肤或肠道，或影响两种器官。由于FA不能通过实验室程序或体内试验得到可靠的诊断，临床医生只能建议采用长时间的食物排查，包括喂食以前未食用的成分或含有充分水解蛋白来源的饮食。在开始这种食物排查8周后，90%以上患有FA的犬和猫的FA临床症状减轻。在记录到临床症状有显著改善或恢复正常后，最终确认FA的诊断需要在喂食旧饮食后引起临床症状的爆发，通常随后症状会减弱，然后再喂食物排查。随后可以进行单一成分的激发试验，以确定哪些成分引起了过敏反应。然而，目前还没有明确的共识，兽医应该等多久才能决定，因为没有复发症状，可以认为患病动物对新喂养的食物不过敏。寻找排除对(完全)饮食或其成分过敏所需的最短时间是很重要的，这有助于增加宠主遵守这一众所周知的漫长过程，特别是在对单个食物成分进行连续激发时。

 

Clinical scenario

临床案例

A two-year-old male castrated Labrador retriever has a one-year history of chronic recurrent diarrhea and skin lesions consistent with atopic dermatitis. It is fed a salmon and potato-based commercial diet, and you thus suspect that it suffers from an allergy to this diet. You initiated an 8-week-long elimination diet with an extensive hydrolysate-containing diet, and cutaneous and digestive signs rapidly decreased in frequency and severity before eventually disappearing. The reintroduction of the salmon-and-potato diet resulted in a flare of signs within the first day. After signs abated again with the hydrolyzed diet, you confirmed a FA and you decided to identify which ingredient(s) caused this flare. You thus decided to first add salmon to the hydrolyzed diet. After 1 week, this dog was still is free of symptoms. You wonder if this short challenge duration was sufficient to rule-out a salmon allergy in this dog before proceeding with a second oral provocation with potatoes.

一只两岁的雄性已去势拉布拉多寻回犬有一年的慢性反复腹泻和皮肤病变与特应性皮炎一致的病史。它被喂食以鲑鱼和土豆为基础的商业饮食，因此你怀疑它对这种饮食过敏。你开始了8周的食物排查，包括大量含有水解液的饮食，皮肤和消化症状在频率和严重程度上迅速下降，最终消失。重新引入鲑鱼和土豆的饮食，在第一天就出现了明显症状。在使用水解饮食后症状再次减弱后，您确认了FA，并决定确定是哪些成分引起了这种急性发作。因此，您决定先将三文鱼添加到水解饲料中。1周后，这只犬仍然没有症状。你想知道，在继续用土豆进行第二次口服激发之前，短时间的激发是否足以排除这只犬对鲑鱼过敏。

 

Structured question

结构性问题

In a dog or a cat with a skin-manifesting FA, what is the time needed for clinical signs to flare after an oral food challenge (OFC) with an ingredient to which it is allergic?

对于皮肤出现FA的犬或猫，在使用其过敏成分的口服食物激发(OFC)后，临床症状发作需要多长时间?

 

Search strategy

搜索策略

We searched the Web of Science Core Collection and CAB Abstract databases on October 23, 2019, with the following sensitive Boolean query string: (dog or dogs or canine or cat or cats or feline) and (food* or diet*) and (allerg* or hypersens*) not (human* or child*). There were no restrictions for publication dates or languages. We did not search conference abstracts or include review papers because of our need for original patient data. Finally, we scanned the bibliography of each selected article as well as those of previously-published critically-appraised topics on CAFRs in dogs and cats for additional references.

我们于2019年10月23日搜索了Web of Science Core Collection和CAB Abstract数据库，使用以下敏感的布尔查询字符串:(犬或犬或犬或猫或猫或猫)和(食物*或饮食*)和(过敏*或hypersens*)而不是(人类*或儿童*)。对出版日期或语言没有限制。我们没有搜索会议摘要或包括综述论文，因为我们需要原始的患病动物数据。最后，我们浏览了每一篇选定文章的参考书目，以及先前发表的关于猫犬CAFR的经过严格评估的主题，以获得额外的参考。

 

Identified evidence

确定证据

Our query of the Web of Science and CAB Abstracts databases identified 489 and 877 articles, respectively. Among these, we searched for papers that reported specific information on the time for a flare of clinical signs to occur during the OFCs that followed elimination diets in dogs and cats with skin-manifesting FAs. For the purpose of this study, we considered OFCs made both with the original diet and its composing ingredients. Thus, we selected nine and two papers relevant to dogs and cats with FAs, respectively. After scanning the bibliography of these articles and those of the previously published critically-appraised topics on CAFRs of companion animals, we identified three additional papers. We subsequently eliminated one report whose cases had been included in a second article published 2 years later. Ultimately, the total number of articles selected was 13 of whom 11 were large case series or clinical trials and the other two were case reports of one animal each. All but two studies involved dogs and cats with spontaneously-arising FAs occurring in a natural home environment, the last two were from dogs with spontaneous FAs who lived in a university-based laboratory animal facility.

我们查询了Web of Science和CAB Abstracts数据库，分别发现了489和877篇文章。在这些研究中，我们搜索了报告了在有皮肤FAs的犬和猫的排除饮食之后，OFC期间出现大量临床症状的具体信息的论文。为了研究的目的，我们考虑了用旧饮食及其组成成分制成的OFC。因此，我们分别选择了9篇和2篇与犬和猫FA相关的论文。在浏览了这些文章的参考书目以及之前发表的关于伴侣动物CAFR的评论性主题的参考书目后，我们确定了另外三篇论文。我们随后删除了一篇两年后发表的第二篇文章中包含的病例报告。最终选择的文章总数为13篇，其中11篇为大型病例系列或临床试验，2篇为病例报告，每只动物1例。除了两项研究外，所有的研究都涉及在自然的家庭环境中自发产生FA的犬和猫，最后两项研究来自生活在大学实验室动物设施中自发产生FA的犬。

 

The patients included in the studies had a worldwide distribution, as five articles reported data from pets seen in the USA two articles contained cases from the United Kingdom and France and there was one article from the Netherlands, Japan and Australia. The last paper included dogs from Switzerland and the USA. The studies spanned nearly 30 years, as they were published between 1990 and 2019.

纳入研究的患病动物分布在世界各地，五篇文章报告了来自美国宠物的数据，两篇文章包含来自英国和法国的病例，还有一篇文章来自荷兰、日本和澳大利亚。最后一篇论文包括了来自瑞士和美国的犬。这些研究跨度近30年，发表于1990年至2019年之间。

 

Evaluation of evidence

评估证据

Altogether, we reviewed the study results of nine papers that included 234 dogs and four articles containing data from 83 cats. As multiple OFCs could be done in the same patient or not all animals included were subjected to an OFC, we were able to compile 315 and 72 times to flare (TTF) after an OFC in dogs and cats, respectively. The full details are available in the Supplementary Tables 1 (dogs) and 2 (cats).

我们总共回顾了包括234只犬的9篇论文和包含83只猫数据的4篇文章的研究结果。由于可以在同一患病动物中进行多个OFC，或者不是所有纳入的动物都遭受OFC，我们能够在犬和猫的OFC之后分别编译315次和72次的TTF。详情见补充表一(犬)及表二(猫)。

 

There was some variation in the reporting of TTF in the different studies. While the case reports and three of the large case series specifically mentioned the TTF after OFCs in individual days, all other papers included TTF data in ranges two to sevenday long.

不同研究对TTF的报道存在一定差异。虽然案例报告和三个大型案例系列特别提到了在OFC之后的个别天的TTF，但所有其他论文都包含了2至7天的TTF数据。

 

When regrouping all cases together, the TTF after OFCs are depicted in Fig. 1. About 9% of dogs and 27% of cats exhibited a flare of clinical signs on the first day after an OFC; 21% of dogs and 29% of cats had such relapse by the end of the second day. The time needed for half of the dogs and cats to exhibit a deterioration of clinical signs (TTF50) was 5 and 4 days, respectively. Similarly, the TTF80 was 7 days for both species, and the TTF90 was 14 and 7 days for dogs and cats, respectively. By 14 days after an OFC, nearly all food-allergic patients from both species had had a relapse of clinical signs.

将所有案例重新组合在一起时，OFC后的TTF如图1所示。约9%的犬和27%的猫在有OFC后的第一天表现出明显的临床症状;21%的犬和29%的猫在第二天结束时复发。半数犬和猫出现临床症状恶化(TTF50)所需时间分别为5天和4天。两种动物的TTF80均为7 d，犬和猫的TTF90分别为14和7 d。在OFC后的14天，几乎所有来自两个物种的食物过敏患病动物的临床症状都复发了。

 

Two factors limit our interpretation of the data: 1) there was only a small number of animals (especially cats) with observations reported in the first day that follows an OFC, and, 2) several studies only included the TTF data in durations encompassing several days. Both factors likely led to an underreporting of TTF in the first hours or day after an OFC, the time when IgE-mediated acute allergic reactions typically are recognized.

两个因素限制了我们对数据的解释:1)只有少数动物(尤其是猫)在OFC之后的第一天进行了观察，2)一些研究只包括了持续数天的TTF数据。这两种因素都可能导致OFC后最初几个小时或一天的TTF漏报，这段时间通常是IgE介导的急性过敏反应被识别出来的时间。

 

Conclusion and implication for practitioners

结论及对实践者的启示 

Veterinary clinicians performing an OFC need to wait for 14 and 7 days for more than 90% of dogs and cats with a skin-manifesting FA to have a flare of clinical signs (either skin lesions or pruritus), respectively. Despite the limitations highlighted above, the relatively low number of dogs and cats exhibiting a flare of cutaneous signs on the first day after an OFC suggest that, in these species, FAs might have more often a cell- rather than IgE-mediated pathogenesis. This hypothesis could be one of the factors behind the low accuracy of foodspecific IgE serological tests.

执行OFC的兽医临床医生需要等待14天和7天，分别为超过90%的皮肤显示FA的犬和猫出现明显的临床症状(皮肤病变或瘙痒)。尽管有上述所强调的局限性，但在OFC发生后的第一天出现皮肤症状的犬和猫的数量相对较少，这表明，在这些物种中，FA可能更多的是由细胞而不是IgE介导的发病机制。这一假设可能是食物特异性IgE血清学检测准确性低的原因之一。

 

Future research needs

未来的研究需要

Studies need to better document the flares that occur on the first day--especially in the first hours--after an OFC to establish the specific percentage of dogs and cats likely to have IgE-mediated FAs. Furthermore, as none of the papers reviewed herein provided sufficient details on the protocol of OFCs, there is a critical research need for the establishment of a standard OFC regimen with both commercial or homemade diets or single ingredients. In particular, the quantity of food provided, the type of diet (raw, cooked, a mix thereof) and the need, or lack thereof, for an escalating quantity and/or frequency of administration need to be investigated and harmonized.

研究需要更好地记录OFC后第一天发生的急性发作，特别是在头几个小时内，以确定可能患有IgE介导的FA的犬和猫的具体比例。此外，由于本文所审查的论文都没有提供关于OFC方案的足够细节，因此，建立一种包括商业或自制饮食或单一成分的标准OFC方案是至关重要的研究需要。特别是，需要调查和协调提供的食物数量、饮食类型(生的、熟的、混合的)以及对不断增加的服药数量和/或服药频率的需要或缺乏。

 

杨先生