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Food allergy in dogs and cats; current perspectives on etiology, diagnosis, and management
犬和猫的食物过敏;目前对病因、诊断和治疗的看法
Hilary A. Jackson, BVM&S, DACVD, DECVD*
翻译：王帆
ABSTRACT
摘要
Food allergy is a recognized clinical entity in dogs and cats and is an important differential to consider in the workup of a pruritic animal. Food can be a trigger factor for canine atopic dermatitis, and food allergy may coexist with feline atopic skin syndrome. Other clinical signs such as urticaria, recurrent pyoderma, and dorsolumbar pruritus can be seen in dogs, and urticaria, conjunctivitis, and respiratory signs can be seen in cats. In both species, gastrointestinal signs may be present. The pathogenesis in dogs and cats is complex and incompletely understood, which limits the development of reliable diagnostic laboratory tests. The diagnosis currently relies on an appropriately performed diet trial with subsequent provocation. This paper briefly reviews food allergies in people and explores our current knowledge of the disorder in dogs and cats.
食物过敏在犬和猫中是一种公认的临床疾病，在对有瘙痒的动物进行检查时，食物过敏是一个需要考虑的重要鉴别。食物可能是犬特应性皮炎的触发因素，食物过敏可能与猫特应性皮肤综合征共存。其他临床症状如荨麻疹、复发性脓皮病和背腰瘙痒可见于犬，荨麻疹、结膜炎和呼吸系统症状可见于猫。在这两个物种中，都可能出现胃肠道症状。犬和猫的发病机制复杂且不完全清楚，这限制了可靠诊断实验室检测的发展。目前诊断依赖于适当的食物排查试验和随后的激发试验。本文简要回顾了人类的食物过敏，并探讨了我们目前对犬和猫的疾病的认识。
Definition and Pathogenesis
定义和发病机制
Adverse food reactions can either have a true immunological basis (food allergy) or can occur as a result of toxic, pharmacological, or idiosyncratic reactions to food (food intolerance). Examples of food intolerance in pets are lactose intolerance, chocolate poisoning (dogs), and bacterial toxins contaminating diets leading to enteritis. There are no confirmed reports of adverse food reactions in dogs and cats causing recurrent or ongoing pruritus with or without gastrointestinal signs. There is evidence of an immunological basis for cutaneous adverse food reactions in dogs; there is a paucity of research into the condition in cats. Consequently, this review will focus on food allergy.
食物不良反应可以有真正的免疫学基础(食物过敏)，也可以是对食物的毒性、药理学或特异质反应(食物不耐受)的结果。宠物食物不耐受的例子包括乳糖不耐受、巧克力中毒(犬)和导致肠炎的细菌毒素污染饮食。目前关于犬和猫的食物不良反应引起反复或持续的瘙痒伴或不伴胃肠道症状没有明确报道。有证据表明，犬的皮肤食物不良反应有免疫学基础;关于猫的这种情况的研究很少。因此，本文就食物过敏作一综述。
Food allergy is the result of the breakdown of immunological tolerance to food that results in immunoglobulin E (IgE) or non-IgE-mediated immune disorders resulting in clinical disease. In the normal individual, food allergens are presented by local dendritic cells in the gastrointestinal tract and stimulate a regulatory T cell (T-reg) response in the local lymph node. In patients with food allergy, this process is compromised and a specific Th2 response is triggered, which is responsible for B-cell immunoglobulin class switching, and an allergen-specific IgE response is initiated. A non-IgE, cell-mediated reaction may also develop or a combination of both reactions.
食物过敏是机体对食物的免疫耐受被打破，导致免疫球蛋白E (IgE)或非IgE介导的免疫紊乱而引起的临床疾病。在正常个体中，食物过敏原由胃肠道局部的树突状细胞提呈，并刺激局部淋巴结的调节性T细胞(T-reg)反应。在食物过敏患者中，这一过程受到损害，并触发特异性Th2反应，Th2反应负责B细胞免疫球蛋白类别转换，并启动过敏原特异性IgE反应。也可发生非IgE的、细胞介导的反应或两种反应的组合。
Humans
人类
Most cases of food allergy in people are IgE mediated, and there is consistent evidence for food as a trigger in some atopic children. Cell-mediated food allergy in humans is a heterogeneous group of diseases such as eosinophilic oesophagitis and food protein-induced allergic proctocolitis, which primarily affect the gastrointestinal tract.
大多数人的食物过敏是由IgE介导的，有一致的证据表明，食物是一些儿童特应性疾病的触发因素。人类细胞介导的食物过敏是一类异质性疾病，如嗜酸性食管炎和食物蛋白诱导的过敏性直结肠炎，主要影响胃肠道。
The prevalence of (IgE-mediated) food allergy in humans is estimated at around 2.8% in infants rising to 10% at 2 years of age and falling to 7% in adolescents. In this age group milk, tree nuts, peanut, and shellfish are the most common allergens. The same authors estimated a prevalence of 10.8% in adults. Certain allergies such as those to peanuts, tree nuts, and shellfish are more likely to persist whereas milk and egg allergies usually resolve. It is estimated that around 33% of children with moderate to severe AD have food allergy.
据估计，人类(IgE介导)食物过敏的患病率在婴儿中约为2.8%，在两岁时上升至10%，在青少年中下降至7%。在这个年龄段，牛奶、树坚果、花生和贝类是最常见的过敏原。同样的作者估计成人的患病率为10.8%。某些过敏，如花生、树坚果和贝类，更有可能持续存在，而牛奶和鸡蛋过敏通常会消退。据估计，大约33%的中度至重度AD患儿有食物过敏。
The development of food allergy is a complex interaction between genetics, epigenetics, and environmental factors leading to a breakdown in normal tolerance to dietary components. The higher incidence in infants may reflect an immature immune system. It would also appear that specific timing can be critical in infants and the composition of the gut microbiota early in life could be important for the development of allergy in the future.
食物过敏的发展是遗传、表观遗传和环境因素之间复杂的相互作用，导致对饮食成分的正常耐受性崩溃。婴儿较高的发病率可能反映了不成熟的免疫系统。似乎特定的时间对婴儿来说也很关键，生命早期肠道微生物群的组成可能对未来过敏的发展很重要。
In addition to the gastrointestinal route, epicutaneous exposure to allergens is thought to be important in this age group, especially in those affected with AD where inflamed skin facilitates allergen absorption.
除了胃肠道途径外，皮肤接触过敏原被认为对这一年龄组很重要，特别是对那些患有AD的人来说，有炎症的皮肤促进过敏原的吸收。
There is insufficient evidence to support the maternal avoidance of foods during pregnancy and lactation or the feeding of a hydrolyzed milk formula and breastfeeding postnatally.
没有足够的证据支持母亲应该在怀孕和哺乳期间避免食物或喂养水解配方奶和产后母乳喂养。
Class II sensitization to food allergens is more common in later life and occurs after a primary sensitization to pollen allergens with subsequent crossreactivity with homologous epitopes in vegetables and fruits, the pollen-food allergy syndrome (PFAS).7 The particular foods triggering PFAS varies geographically with birch pollen being the primary sensitizer in Europe.
对食物过敏原的II类致敏在晚年更常见，发生在对花粉过敏原的初次致敏之后，随后与蔬菜和水果中的同源表位发生交叉反应，即花粉-食物过敏综合征(PFAS)引发PFAS的特定食物在地理上有所不同，在欧洲桦树花粉是主要的致敏剂。
Adult sensitization to food allergens can also be percutaneous with dairy, wheat, and soy allergies developing as a consequence of the use of skin care products containing these ingredients.
成人对食物过敏原的致敏也可以是经皮的，使用含有乳制品、小麦和大豆这些成分的护肤品时出现过敏反应。
Dogs
犬
There is less known about the pathogenesis of food allergy in dogs when compared to humans. To develop a hypersensitivity reaction, there is a loss of tolerance to food antigens, which likely arises from a genetic predisposition, alterations in gastrointestinal permeability, local immune surveillance, and dysbiosis of the gut microbiome. The prevalence of food-induced disease is greater in dogs less than 12 months of age with another peak in older dogs. A recent review of the onset of food-induced clinical signs in dogs was reported to be less than 6 months (22%) to less than 12 months (38%) with the range extending to 13 years of age. Estimates of the prevelance in dogs vary between 25% and 49% of allergic dogs and between 8% and 62% of dogs with pruritus. In many cases, the clinical presentation is of an AD phenotype (9% to 50%) and food allergens can be demonstrated to cause a flare of the disease.
与人类相比，关于犬的食物过敏的发病机制知之甚少。一旦对食物抗原的耐受性缺失，就会出现过敏反应，这可能是由于遗传易感性、胃肠道通透性改变、局部免疫监视和肠道微生物群的生态失调。食源诱发性疾病的患病率在12个月以下的犬中更高，在老年犬中另一个高峰。最近一项关于犬出现食物引起的临床症状的综述报告称，发病年龄在6个月(22%)至12个月(38%)之间，范围可达13岁。据估计，过敏症患犬发病率在25%-49%，瘙痒患犬发病率在8%-62%不等。在许多病例中，临床表现为AD表型(9% ~ 50%)，食物过敏原可引起疾病发作。
Although there is evidence that IgE is involved in the pathogenesis of canine food allergy, lymphocyte blastogenic responses to food allergens also showed a strong correlation with offending allergens in dogs with a confirmed food allergy. Furthermore, the reactivity was attenuated when the dogs were fed an elimination diet. This supports a mixed immunological reaction in canine food allergy; while Th cells can stimulate a B-cell response, a delayed-type hypersensitivity can also be initiated.
虽然有证据表明IgE参与了犬食物过敏的发病过程，但在确诊食物过敏的犬中，对食物过敏原的淋巴细胞母细胞反应也显示出与致病过敏原的强相关性。此外，当犬进行食物排查时，反应性减弱。这支持了犬食物过敏的混合免疫反应;虽然Th细胞可以刺激B细胞应答，但也可以启动迟发型超敏反应。
There is a paucity of studies investigating the development of canine food allergy and most researchers have focused on AD. A prospective study followed 90 West Highland White Terrier puppies, a breed known for developing AD, for the first 3 years of life. Of this group, 52% developed clinical signs consistent with AD, and of this 17% were confirmed to have food-related AD.
目前关于犬类食物过敏发生发展的研究很少，大多数研究人员都集中在AD上。一项前瞻性研究跟踪了90只西高地白梗幼犬(一种以患AD而闻名的品种)3岁前的情况。在这一人群中，52%出现了符合AD的临床症状，其中17%被证实患与食物相关的AD。
In a small study looking at the expression of Foxp in the canine gut, this was shown to increase with age, suggesting a progressive establishment of oral tolerance. The effect of diet on the gut microbiota has also been studied. The gut microflora was compared between 2 groups of dogs, 1 on a raw diet and the other on commercial feed. The raw-fed dogs were found to have a greater diversity of bacteria in their gut but also a higher incidence of opportunistic pathogens such as Clostridia perfringens, and in a small study feeding a raw meat diet to Staffordshire Bull Terriers with AD, changes in the skin transcriptome were seen. A number of investigators have looked at whether a dietary modification in pregnancy or early puppyhood could influence the development of AD in later life. In a case-controlled Swedish study, the feeding of noncommercial foods to the pregnant bitch had a protective effect on the development of AD in West Highland White Terriers, Boxers, and Bull Terriers. In an owner-reported survey, in Finland an association between the consumption of 80% or more of the diet as kibble with added mixed oils and sugary fruit and the development of adult-onset AD was reported. It should be noted that a causal relationship was not established in this study and other management variables of the puppies were not addressed. Whether dietary modifications in these cited studies had an influence on the development of food-induced AD in the dogs was not reported. Further research into whether dysbiosis of the gastrointestinal microbiome is a factor in the development of canine allergic diseases is required.
在一项小型研究中，研究人员观察了Foxp在犬肠道中的表达情况，发现它会随着年龄的增长而增加，这表明口服耐受的逐步建立。饮食对肠道菌群的影响也有研究。比较两组犬的肠道菌群，一组饲喂生食，另一组饲喂市售饲料。研究发现，生食犬的肠道细菌多样性更大，但条件致病性病原体(如产气荚膜梭菌)的发生率更高。在一项小型研究中，给患AD的斯塔福斗牛梗喂食生肉，观察到皮肤转录组发生了变化。许多研究人员都在研究孕期或幼年期的饮食调整是否会影响晚年AD的发生。在瑞典的一项病例对照研究中，给怀孕母犬喂食非商业性食物对西高地白梗、拳师犬和斗牛梗的AD发生具有保护作用。在芬兰一项业宠主报告的调查中，据报道，摄入≥80%的添加了混合油和含糖水果的犬粮与成年发病型AD之间存在关联。值得注意的是，本研究中没有建立因果关系，也没有处理幼犬的其他管理变量。在这些被引用的研究中，饮食调整是否对犬的食物诱导的AD的发展有影响没有报道。需要进一步研究胃肠道微生物群的失调是否是犬过敏性疾病发生的一个因素。
Allergens
过敏原
The most common food protein allergens range in size between 15 and 40 kDa although some smaller or larger proteins can be allergenic. They are generally resistant to digestion.
最常见的食物蛋白质过敏原的大小在15到40 kDa之间，但一些较更小或更大的蛋白质也可能引起过敏。它们通常不容易消化。
A review of allergens reported by owners to provoke a clinical response in cats and dogs with a presumed food allergy between 1985 and 2015 suggested beef, dairy, chicken, and wheat were most common in dogs and beef, fish, and chicken in cats. Our knowledge of clinically relevant componentderived diagnostic (CRD) allergens (specific epitopes) in animals is minimal and was reviewed 2017. To date, bovine serum albumin (Bos d6), phosphoglutaminase, and bovine IgG (Bos d7) have been identified in dogs with a clinical allergy to beef. Five dogs with clinical hypersensitivity to hens egg had allergen-specific IgE to ovomucoid (Gal d1), ovalbumin (Gal d2), and ovotransferrin (Gal d3), and dogs with confirmed fish (cod) allergy had serum IgE specific for tropomyosin and enolase (Gad m2). Knowledge of CRD will help with diagnostics and discrimination between cross and cosensitization in the future. A recent investigation compared 3 groups of dogs; first, those consuming a diet with no chicken but no clinical hypersensitivity or positive serum IgE to chicken; second, a group with AD and positive IgE titers to chicken (whether the dogs had clinical reactivity to chicken was unknown); and finally, a group of dogs with clinical chicken hypersensitivity confirmed by food challenge. Using immunoblotting and mass spectrometry, 7 major chicken allergens were identified in the chicken-sensitized dogs, 3 of which were recognized allergens in humans and all of which were common to other food sources such as fish, meats, or plants. Serum IgE cross-reactivity was demonstrated by the same researchers between chicken and fish when serum from dogs with suspected food allergy was examined using ELISA, inhibition ELISA, and inhibition immunoblots. Further serological cross-reaction in the serum of suspected food-allergic dogs has been demonstrated between ruminants (ie, beef and lamb and cow milk), poultry, and grains, as well as unrelated sources such as pork and ruminant.
一项关于1985年至2015年期间宠主报告的过敏原的综述表明，牛肉、乳制品、鸡肉和小麦在犬中最常见，而牛肉、鱼和鸡肉在猫中最常见。这些过敏原引起了猫和犬的临床反应。我们对动物中临床相关的成分衍生的诊断(CRD)过敏原(特异性表位)的知识很少，并在2017年进行了综述。到目前为止，牛血清白蛋白(Bos d6)、磷酸谷氨酰胺酶和牛IgG (Bos d7)已经在对牛肉临床过敏的犬中鉴定出来。对鸡蛋临床过敏的5只犬对卵黏蛋白(半乳糖d1)、卵清蛋白(半乳糖d2)和卵转铁蛋白(半乳糖d3)有过敏原特异性IgE，确诊对鱼(鳕鱼)过敏的犬对原肌球蛋白和烯醇化酶(Gad m2)有血清特异性IgE。对CRD的了解将有助于未来的诊断和区分交叉敏化和共敏化。最近的一项调查比较了3组犬;第一组为饮食中不含鸡肉但无临床超敏反应或对鸡肉无血清IgE阳性的人群;二是对鸡IgE滴度阳性的AD组(犬对鸡是否有临床反应尚不清楚);最后，一组临床对鸡过敏的犬通过食物激发得到了证实。通过免疫印迹和质谱分析，在鸡致敏的犬中鉴定出7种主要的鸡过敏原，其中3种是已知的人类过敏原，所有这些过敏原都是其他食物来源(如鱼、肉或植物)的共同过敏原。用酶联免疫吸附试验(ELISA)、抑制ELISA和抑制免疫印迹法检测可疑食物过敏犬的血清，发现鸡和鱼的血清IgE存在交叉反应。在疑似食物过敏的犬的血清中，反刍动物(如牛肉、羊肉和牛奶)、家禽和谷物，以及不相关的来源(如猪肉和反刍动物)之间有进一步的血清学交叉反应。
It is currently unknown whether class II sensitization occurs in dogs. Between 10 and 35% of dogs are naturally sensitized to birch; however, it is unknown whether this is specifically Bet v1, the major crossreacting allergen in humans, and whether this has clinical relevance to the ingestion of vegetables and fruit by dogs has not been investigated. In Japan, sensitization to Japanese cedar is a common airborne allergen with subsequent PFAS developing to tomato in people. This has been reported in an individual dog.
目前尚不清楚II类致敏是否发生在犬身上。10%到35%的犬天生对桦树过敏;然而，尚不清楚这是否是人类主要交叉反应过敏原betv1的特异性，也未调查这是否与犬摄入蔬菜和水果具有临床相关性。在日本，对杉木的致敏是一种常见的空气传播过敏原，随后PFAS在人体内发展到番茄。这在一只犬身上有过报道。
While in some cases the specific allergens responsible for clinical reactions in sensitized dogs have been identified the clinical relevance of positive results in dogs with no signs of allergy and the significance of cross-reactivity with homologous allergens remains to be investigated. In theory, exposure to “hidden” proteins such as traces of bovine serum albumin and casein in vaccinations or infestation with Toxocara canis may act as sensitizing allergens.
虽然在某些病例中，引起致敏犬临床反应的特异性过敏原已被确定，但在没有过敏症状的犬中，阳性结果的临床相关性以及与同源过敏原的交叉反应的意义仍有待研究。理论上，接触“隐藏”蛋白(如接种疫苗时残留的牛血清白蛋白和酪蛋白)或感染犬弓首线虫可能成为致敏过敏原。
The research reviewed herein has focused on an IgE-mediated pathogenesis, and further work needs to be directed at the possibility of dysregulation in other immune pathways.
本文综述的研究主要集中在IgE介导的发病机制上，进一步的工作需要针对其他免疫途径失调的可能性。
Clinical Presentation
临床表现
Dogs
犬
In a Swiss study in which the allergic population was compared with all registered dogs, West Highland White Terriers, Rhodesian Ridgebacks, and Pugs were predisposed to food allergy, supporting a genetic predisposition to the disease. It should be noted however that these breeds are also commonly affected by canine AD. In the same study, gastrointestinal signs were more common in the affected population with food allergy and clinical signs tended to develop earlier, 48% in the food-allergic dogs (< 1 year) as compared with 16% of dogs with AD.
在瑞士的一项研究中，过敏患犬与所有登记的犬进行了比较，西高地白梗、罗得西亚脊背犬和巴哥犬易患食物过敏，这支持了对这种疾病的遗传易感性。值得注意的是，这些品种也经常患犬AD。在同一项研究中，胃肠道症状在食物过敏的患犬中更为常见，临床症状往往出现得更早，48%的食物过敏犬(＜1岁)，而患有AD的犬只有16%。
Food-allergic dogs with the atopic phenotype present with pruritus affecting the paws, ventral abdomen, axillae, groin and perineum, face, and ears. Not all these body sites will be affected, and some may present with only pedal pruritus or recurrent otitis for example. Although in young dogs clinical signs may initially be controlled with diet, some of these dogs will subsequently develop environmental hypersensitivities later in life.
具有特应性表型的食物过敏犬的爪子、腹部、腋窝、腹股沟和会阴、面部和耳朵出现瘙痒。并非所有这些机体部位都会患病，有些部位可能只出现脚部瘙痒或复发性耳炎等症状。虽然幼犬的临床症状最初可以通过饮食来控制，但其中一些犬在以后的生活中会发展为环境过敏。
Other dogs can present with urticaria, recurrent pyoderma, or dorsolumbar pruritus and may also exhibit gastrointestinal signs manifested by soft feces, flatulence, intermittent diarrhea, and clinical signs consistent with colitis. Conjunctivitis and sneezing have also been reported in a small number of dogs.
其他犬可表现为荨麻疹、复发性脓皮病或腰背瘙痒，也可表现为胃肠道症状，表现为软便、胀气、间歇性腹泻和与结肠炎一致的临床症状。结膜炎和打喷嚏在少数犬也有报道。
As food allergy can develop at any age, the onset of pruritus, recurrent otitis, and or recurrent pyoderma should be considered as a differential diagnosis for any dog in which parasite infestation and other causes of pruritus have been comprehensively ruled out.
由于食物过敏可以在任何年龄发生，瘙痒症、复发性耳炎和/或复发性脓皮病的发作应被视为任何犬的鉴别诊断，其中寄生虫感染和其他原因的瘙痒症已被全面排除。
Cats
猫
The figures for cats are similar with the onset of clinical signs before 12 months in 27% of cases where reported. Cats usually present with pruritus, which may be associated with self-induced symmetrical alopecia, miliary dermatitis, head and neck pruritus, the eosinophilic granuloma complex, or a combination of patterns. Extracutaneous signs such as conjunctivitis (12%), gastrointestinal (18%), and respiratory signs may also be present.
在报告的病例中，27%的猫病例在12个月前出现临床症状。猫通常表现为瘙痒，这可能与自损性对称性脱毛、粟粒性皮炎、头颈部瘙痒、嗜酸性肉芽肿综合征或多种模式的组合有关。还可能出现结膜炎(12%)、胃肠道(18%)和呼吸系统症状等皮肤外症状。
Diagnosis
诊断
The diagnosis of food allergy in dogs and cats currently relies on performing a diet trial and subsequent provocation. This is currently the only reliable diagnostic test. This should not contain any previously consumed foods and be based on a “novel” or hydrolyzed protein diet. Selection of an appropriate diet therefore relies on a comprehensive diet history obtained from the owner and any other individuals who take care of the animal. Identification and sourcing novel proteins can be challenging and are potentially complicated by the possibility of crossreaction with apparently unrelated food sources as discussed previously. For this reason, hydrolyzed diets are commonly used (Figure 1). Pivotal to the performance of a successful diet trial are owner education and compliance. Time needs to be set aside within a busy clinical setting to explain the premise of the trial and address any potential obstacles, which might arise. Using trained technicians to make regular phone contact with owners during the trial will improve compliance.
目前，犬和猫食物过敏的诊断依赖于进行食物试验和随后的激发试验。这是目前唯一可靠的诊断试验。不应含有任何先前食用的食物，应以“新型”或水解蛋白饮食为基础。因此，选择合适的饮食依赖于从 宠主任何其他照顾动物的人那里获得的全面的饮食史。如前所述，鉴定和寻找新的蛋白质可能具有挑战性，并且可能因与明显无关的食物来源发生交叉反应而变得复杂。因此，通常使用水解食物(图1)。食物试验成功的关键是宠主的教育和依从性。在繁忙的临床环境中，需要留出时间来解释试验的前提，并解决可能出现的任何潜在障碍。使用训练有素的技术人员在试验期间定期与宠主进行电话联系将提高依从性。
Composition of the diet
食物组成
It is increasingly difficult to source a “novel” protein source, ie, one the pet has not previously eaten. In this context, it has been suggested that employing insect-based diets to which the dogs have not had previous exposure and that contain highly valuable digestible proteins might be a reasonable option. However, these contain a source of allergen that is phylogenetically related to house dust and storage mites. Serum containing house dust and storage mite-specific IgE was collected from clinically normal and dogs with confirmed AD. In both groups, the IgE bound to insect (mealworm) proteins on a Western blot with no significant difference seen between the groups. It is not currently clear whether these findings represent clinically relevant allergy, sensitization, or carbohydrate moieties causing false positive results. However, a novel protein diet trial based on insects in dogs previously sensitized to house dust and storage mites may not be the optimal choice.
现在越来越难找到一种“新型”蛋白质，也就是宠物以前没有吃过的蛋白质。在这种情况下，有人建议，使用以昆虫为基础的食物，这些食物是犬以前没有接触过的，并且含有高价值的可消化蛋白质可能是一个合理的选择。然而，这些含有过敏原的来源是演化史相关的房屋灰尘和储物螨。从临床正常和确诊AD的犬中收集含有屋尘和储存螨特异性IgE的血清。在两组中，IgE均与昆虫(粉虫)蛋白结合，组间无显著差异。目前尚不清楚这些发现是否代表有临床意义的过敏、致敏或导致假阳性结果的碳水化合物部分。然而，一项基于先前对屋尘和储物螨过敏的犬的昆虫的新型蛋白质饮食试验可能不是最佳选择。
An additional problem is the potential for residues of unlisted food sources to be present in the diet. Various studies have examined pet foods proposed as novel protein diets using PCR, ELISA, or direct microscopy and demonstrated foreign elements in 33 to 83% of these diets, reviewed by Olivry and Mueller. The hydrolyzed diets examined did not have food contaminants present.
另一个问题是饮食中可能存在未列出的食物来源的残留物。各种研究使用PCR、ELISA或直接显微镜检查了被提出作为新型蛋白质饮食的宠物食品，并发现其中33% ~ 83%有外来元素，由oliver和Mueller进行了综述。所检测的水解饲料不存在食物污染物。
The use of hydrolyzed diets eliminates the requirement to find a novel protein source. The proteins are generally hydrolyzed to a molecular weight < 5 kDa, which theoretically prevents cross-linking of IgE. The antigenicity of a hydrolyzed diet depends on the degree of hydrolysis; for IgE-mediated food allergy, an extensively hydrolyzed diet is optimal; and regular monitoring of the product batches is desirable. Extensively hydrolyzed elemental diets that contain oligopeptides are also available in certain countries. Hydrolyzed diets usually contain a carbohydrate moiety, in this regard cornstarch appears less likely to induce an IgE reaction in dogs and cats than corn flour.
使用水解食物无需寻找新的蛋白质来源。蛋白质一般水解为分子量＜5 kDa，理论上可以防止IgE的交联。水解食物的抗原性取决于水解的程度;对于IgE介导的食物过敏，广泛水解的饮食是最佳的;定期监测产品批次是必要的。某些国家也可获得含有寡肽的广泛水解元素食物。水解饲料通常含有碳水化合物部分，在这方面，玉米淀粉诱发犬和猫IgE反应的可能性比玉米粉小。
A small study demonstrated that 10 dogs with proven chicken allergy did not react clinically to an extensively hydrolyzed poultry feather diet < 1 kDa; however, when the diet was only partially hydrolyzed, 40% of the dogs had clinical reactions.
一项小型研究表明，10只被证实对鸡肉过敏的犬对广泛水解的家禽羽毛饮食< 1 kDa没有临床反应;然而，当饮食只是部分水解时，40%的犬有临床反应。
It has been shown however that hydrolyzed proteins can stimulate T-lymphocytes in dogs with suspected food allergy suggesting that these diets may not be uniformly reliable for diet trials, and this supports a cell-mediated pathway of food allergy in dogs.
然而，有研究表明，水解蛋白可以刺激疑似食物过敏的犬的T淋巴细胞，这表明这些饮食在饮食试验中可能并不完全可靠，这支持了犬食物过敏的细胞介导途径。
Home-cooked diets often are advocated to avoid pet food additives that may cause adverse reactions, although there are no well-documented reports to support this in pets. However, home cooking with a single source of protein should avoid the problem of contamination with foreign proteins in manufactured pet foods discussed above. The diets are usually based on a single protein to which the animal has not been previously exposed; this is usually mixed with a carbohydrate source. Home-cooked diets are usually nutritionally inadequate for maintenance or growth, and clinicians are advised to use recipes available in veterinary textbooks or the services of a diplomate in veterinary nutrition to create balanced diets. In 1 study, 36% of clients preparing home-cooked food for their dogs discontinued the diet trial prematurely. Another study documented a failure rate of 52% of clients, although the failure rate dropped to 27% after better client education was instituted. This emphasizes the importance of client communication if home-cooked diets are used. Clients should also be made aware that preparing home-cooked diets is time consuming and generally more expensive than feeding commercially available foods.
家庭烹饪常被提倡避免可能引起不良反应的宠物食品添加剂，但在宠物中没有充分的记录报告支持这一点。然而，使用单一来源的蛋白质进行家庭烹饪应避免上文所讨论的人造宠物食品中受到外来蛋白质污染的问题。这些饮食通常是基于动物之前没有接触过的单一蛋白质;这通常与碳水化合物混合。家庭烹饪的饮食通常营养不足，无法维持或生长，建议临床医师使用兽医教科书或兽医营养学专科医师提供的食谱来创建平衡的饮食。在一项研究中，36%的客户在为他们的犬准备家庭烹饪食物时提前终止了食物试验。另一项研究记录了52%的客户的失败率，但在实施了更好的宠主教育后，失败率下降到27%。这就强调了如果使用家庭烹饪，与客户沟通的重要性。还应让客户意识到，准备家庭烹饪食物耗时且通常比供应市售食物更昂贵。
The diet trial and challenge
食物试验和激发
The diet trial should be continued for a number of weeks, and based on an analysis of previously published studies, 85% of dogs will have improved by 5 weeks and extending the trial to 8 weeks will be adequate for over 95% of dogs. Similar figures for cats are 80% at 6 weeks and over 90% at 8 weeks. If gastrointestinal signs are concurrently present, then these can resolve more quickly than the cutaneous signs.
食物试验应持续数周，根据对先前发表的研究的分析，85%的犬在5周后会有所改善，而将试验延长至8周将足以满足95%以上的犬。类似的数字在猫6周时是80%，8周时超过90%。如果同时出现胃肠道症状，那么这些症状比皮肤症状消退得更快。
Using anti-inflammatory treatment during the initial phase of the diet trial in dogs has the potential to shorten the duration of the diet trial to 4 to 6 weeks and consequently improve client compliance. Prednisolone tapered to 0.5mg/kg daily was administered for a minimum of 2 weeks until affected dogs exhibited an acceptable level of pruritus as assessed by a validated pruritus analog scale. After discontinuing the prednisolone, the diet was continued for a further 2 weeks without an increase in pruritus before a dietary challenge was performed.
在犬食物试验的初始阶段使用抗炎治疗有可能将犬食物试验的持续时间缩短至4至6周，从而提高宠主依从性。泼尼松龙逐渐减少到每天0.5mg/kg，持续至少2周，直到患犬表现出可接受的瘙痒水平，通过有效的瘙痒模拟评分表评估。停止泼尼松龙治疗后，在进行食物挑战之前，继续食物2周，瘙痒没有增加。
If clinical improvement is sustained, then a dietary challenge must be performed to confirm food allergy and relapse of clinical signs demonstrated. In most allergic skin diseases in dogs and cats, the pruritus waxes and wanes over a period of weeks. Great care must be taken with the interpretation of any apparent improvement in response to a restricted diet as an improvement may be due to concurrent topical antimicrobial treatment, better management, or a seasonal effect. Any pet that improves with a restricted diet should be challenged with its original diet, which should include all treats, scraps, biscuits, chews, and dietary supplements. In the majority of cases, clinicians rely on owners to report a relapse. It is worth pointing out that if an animal has concurrent environmental hypersensitivities, then complete resolution of clinical signs is unlikely to occur. These cases can often be more difficult to interpret as pruritus associated with environmental allergen exposure can wax and wane. The author recommends performing the dietary challenge on a weekend when the owners are with their animals, and if there is seasonality to AD, then performing the diet trial during the winter months may be optimal.
如果临床改善持续出现，则必须进行食物激发，以确认食物过敏和所显示的临床症状复发。在大多数犬和猫的过敏性皮肤病中，瘙痒在几周内会有增有减。对于限制饮食后出现的任何明显改善，必须非常谨慎地解释为改善可能是由于同时进行的外部抗微生物治疗、更好的管理或季节性影响。任何通过食物排查来改善的宠物都应该使用旧饮食激发，包括所有的零食、剩饭、饼干、咀嚼和膳食补充剂。在大多数病例中，临床医师依赖宠主反馈复发情况。值得指出的是，如果动物同时有环境过敏反应，那么临床症状不太可能完全消失。这些病例通常更难以解释，因为与环境过敏原暴露相关的瘙痒可反复发作。作者建议在周末当主人和他们的动物在一起时进行食物激发，如果AD有季节性，那么在冬季进行食物排查试验可能是最佳的。
In 1 recent prospective study including 46 dogs, the median time to relapse after a challenge was 12 hours (range, 1.5 hours to 10 days) with 23.9% within 3 to 6 hours and 60.9% within 12 hours. Pruritus primarily affected the limbs and face. In a previously mentioned study with confirmed chicken-allergic dogs, 44% (4/9) became pruritic within 12 hours of challenge. However, in a retrospective review of publications between 1990 and 2019, only 9% of dogs and 27% of cats reportedly flared within 24 hours. The time to flare of 50% and 90% of dogs, respectively, was 5 and 14 days and for cats was 4 and 7 days. Variability in these reports is likely due to owner observation, specific protein and amount fed, individual variability, and the immune reaction elicited. While an IgE-mediated reaction would be expected to evoke clinical signs within hours of provocation, a mixed or cell-mediated reaction could take considerably longer.
在最近一项包括46只犬的前瞻性研究中，激发后至复发的中位时间为12小时(范围，1.5小时至10天)，23.9%在3-6小时内，60.9%在12小时内。瘙痒主要出现在四肢和面部。在之前提到的一项对鸡过敏的犬进行的研究中，44%(4/9)的犬在激发后12小时内出现瘙痒。然而，在对1990—2019年发表的论文进行的一项回顾性综述中，据报告只有9%的犬和27%的猫在24小时内复发。50%和90%的犬的发作时间分别为5天和14天，猫的发作时间分别为4天和7天。这些报告的差异可能是由于宠主观察、特异性蛋白质和饲喂量、个体差异和引起的免疫反应。虽然IgE介导的反应预计可在激发后数小时内引起临床症状，但混合或细胞介导的反应可能需要相当长的时间。
Other Diagnostic Tests
其它诊断试验
Serum allergy testing for food allergy in dogs has received considerable scrutiny over the years but has been proven to be unreliable in predicting clinical allergy. There are potentially a number of reasons for this. First, serum allergy testing assumes that food allergy in dogs is IgE mediated and serum IgE has a short half-life, and testing is most valid when performed in association with recent exposure.
犬食物过敏的血清过敏原测试多年来受到了相当多的审查，但已被证明在预测临床过敏方面是不可靠的。这可能有很多原因。首先，血清过敏测试假设犬的食物过敏是由IgE介导的，并且血清IgE的半衰期短，并且在与近期暴露相关的情况下进行的测试最有效。
Specific epitopes can vary with processing; the allergens employed for testing may not resemble those present in pet foods; and additionally, positive reactions on serum allergy testing may not predict clinical hypersensitivity. If serum allergy testing is to be used at all, then foods to which serum antibodies are not detected should be selected for the diet trial.
特定的表位可以随加工过程而变化;用于测试的过敏原可能与宠物食品中存在的过敏原不同;此外，血清过敏试验的阳性反应可能不能预测临床过敏。如果要使用血清过敏测试，那么应该选择血清抗体检测不到的食物进行食物试验。
Serum was submitted to 2 laboratories for food specific IgE and IgG from dogs with confirmed food allergy, AD, other skin diseases, and healthy dogs, and the results lacked concordance and were unable to distinguish reliably between the 4 groups.
将确诊为食物过敏、AD等皮肤病犬和健康犬的血清分别送交2个实验室检测食物特异性IgE和IgG，结果缺乏一致性，无法可靠区分4组。
These results have been corroborated by other investigators.
这些结果已得到其他调查人员的证实。
Similarly, food allergen-specific IgE is not reliable as a diagnostic tool in cats.
同样，食物过敏原特异性IgE作为猫的诊断工具也不可靠。
Western blotting (WB) has been examined as a possible diagnostic tool for dogs with suspected food allergy. Serum from dogs with confirmed food allergy was tested against extracts from diets commonly used in diet trials. While dogs with food allergy had more IgE binding to the extracts than nonfood allergic dogs, the WB could not be recommended as a diagnostic tool. Another study performed WB under nonreducing conditions to preserve conformational epitopes; while the food-allergic dogs demonstrated strong IgE binding to beef and milk compared to the nonfood allergic group, the test was not diagnostically useful.
蛋白质印迹法(WB)已被用作疑似食物过敏犬的一种可能的诊断工具。确诊食物过敏的犬的血清与食物中常用的饮食物提取物进行了测试。虽然食物过敏的犬比非食物过敏的犬有更多的IgE与提取物结合，但WB不推荐作为诊断工具。另一项研究在非还原条件下进行WB以保存构象表位;与非食物过敏组相比，食物过敏组的犬显示出与牛肉和牛奶的强IgE结合，但这项测试并没有诊断意义。
Measurement of serum food-specific IgG or saliva testing for food-specific antibodies is of limited value in the diagnosis of canine food allergy.
血清食物特异性IgG检测或唾液食物特异性抗体检测对犬类食物过敏的诊断价值有限。
Intradermal testing has also been shown to be unreliable for the diagnosis of food allergy in dogs. Patch testing has also been evaluated as a diagnostic tool. It was shown to have a good negative predictive value, which could be useful in selecting proteins for an elimination diet trial, and a recent study combining the prick and patch test suggested that this improved the negative predictive value. Patch testing however is not a practical clinical tool as allergens require to be in contact with the skin for 48 hours.
皮内测试也被证明对犬的食物过敏诊断是不可靠的。斑贴试验也被评价为一种诊断工具。研究表明，该方法具有良好的阴性预测值，可用于为食物排查试验选择蛋白质，最近一项结合针刺和斑帖试验的研究表明，该方法提高了阴性预测值。然而，斑贴试验并不是一种实用的临床工具，因为过敏原需要与皮肤接触48小时。
Long-Term Management
长期管理
The majority of dogs and cats with a diagnosis of food allergy are maintained on an avoidance regime after diagnosis. Dietary indiscretions are treated with short-term antipruritic and anti-inflammatory therapy. It is a clinical observation that many pets will tolerate offending foods later in life; however, good long-term studies on this subject have not been performed.
大多数被诊断为食物过敏的犬和猫在诊断后都保持归避饮食。饮食不谨慎可以用短期的止痒和抗炎治疗来治疗。临床观察表明，许多宠物在以后的生活中会容忍令人不快的食物;然而，关于这一问题的长期研究尚未开展。
The goal of food allergy immunotherapy is to induce tolerance to the offending allergens or increase the threshold dose required to elicit an adverse reaction. In at-risk infants, early controlled introduction of peanut/egg is recommended as there is evidence that this is protective against future severe food allergy. Additionally, sublingual and epicutaneous immunotherapy is successfully employed in children to induce desensitization. In dogs, sublingual immunotherapy has been shown to be well tolerated and effective at reducing the severity of reactions to food after 6 months of therapy in 5 dogs.
食物过敏免疫治疗的目的是诱导对致敏原的耐受或增加诱发不良反应所需的阈剂量。对于有风险的婴儿，建议早期有控制地引入花生/鸡蛋，因为有证据表明这可以预防未来的严重食物过敏。此外，舌下和经皮免疫治疗已成功用于儿童，以诱导脱敏。在犬中，5只犬经过6个月的治疗后，舌下免疫疗法显示出良好的耐受性，并有效降低了食物反应的严重程度。
Conclusion
结论
Food allergy is a recognized clinical entity in dogs and cats; however, the details of the aetiopathogenesis remain incompletely understood. At the time of writing, a strict diet trial with a provocative challenge is the standard diagnostic tool. As this relies on owner education and compliance, it presents additional challenges for the busy practitioner. Although commercially available serum allergy tests are available, the results are an unreliable predictor of clinical allergy. Further understanding of the aetiopathogenesis of food allergy in dogs and cats and the clinical relevance of allergen-specific IgE is required to advance our knowledge in this field.
食物过敏在犬和猫中是一种公认的临床疾病;然而，发病机制的细节仍不完全清楚。在撰写本文时，标准的诊断工具是进行严格的食物试验并进行激发试验。由于这依赖于宠主的教育和遵从性，它为忙碌的宠主带来了额外的挑战。虽然市面上有血清过敏试验，但其结果并不是临床过敏的可靠预测指标。进一步了解犬和猫食物过敏的发病机制和过敏原特异性IgE的临床相关性，将有助于提高我们在这一领域的知识。
Figure 1—A 7-month-old domestic short-haired cat with head and neck pruritus before (left) and after a 7-weekdiet trial with a hydrolyzed diet (right).
图1 -一只7个月大的家短毛猫，在进行为期7周的水解饲粮试验前(左)和试验后(右)，出现头颈部瘙痒。
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发表于 2023-9-20 22:02:12
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