本帖最后由 刘欣 于 2019-2-27 18:18 编辑
犬异位性皮炎：诊断和过敏原检测的详细指南 Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification摘要 Abstract 王帆翻译，刘欣校对 背景：犬异位性皮炎（AD）是一种常见的遗传性、炎性和瘙痒性皮肤病。由于此病的遗传因素、病变程度、疾病阶段、继发感染以及与其他非过敏性皮肤病相似的原因，所以其临床表现具有差异，这使犬AD的确诊方法变得复杂。动物过敏性疾病国际委员会小组（ICADA）负责制定一套临床指南，用于帮助执业医师和研究人员诊断犬AD。通过检索网络引文数据库和国际会议摘要，调查与该主题相关的发表文章，并且在必要时结合专家意见。经过全部ICADA委员会批准最终制定了一套指南。 研究结果：本文共回顾了81篇相关的发表文章。指南的制定主要集中于诊断方法的三个方面： 1.排除与犬AD临床症状相似或重叠的皮肤疾病。 2.对犬AD病例的病史调查和临床表现进行详细描述。 3.对比皮内试验和过敏原特异性IgE血清学测试 结论：确诊犬AD的方法是基于满足临床标准以及排除其他有相似临床症状的可能病因。必要时，应把跳蚤梳理、皮肤刮片和细胞学检查作为全面检查的一部分。对于持续性瘙痒和/或并发消化道症状的病例，应进行食物排除激发试验。一旦临床确诊为犬AD，则可进行过敏试验，明确潜在的致病性过敏原，进行过敏原特异性免疫治疗。 Background: Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The variation in clinical presentations, due to genetic factors, extent of the lesions, stage of the disease, secondary infections, as well as resemblance to other non-atopic related skin diseases, can complicate a diagnosis of canine AD. A sub-group of the International Committee for Allergic Diseases in Animals (ICADA) was tasked with the development of a set of practical guidelines that can be used to assist practitioners and researchers in the diagnosis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to the topic, and combined with expert opinion where necessary. The final set of guidelines was approved by the entire ICADA committee. Results: A total of 81 publications relevant for this review were identified. The guidelines generated focus on three aspects of the diagnostic approach: 1. Ruling out of other skin conditions with clinical signs resembling, or overlapping with canine AD. 2. Detailed interpretation of the historical and clinical features of patients affected by canine AD. 3. Allergy testing by intradermal versus allergen-specific IgE serum testing. Conclusions: The diagnosis of canine AD is based on meeting clinical criteria and ruling out other possible causes with similar clinical signs. Flea combing, skin scraping and cytology should be performed, where necessary, as part of a thorough work-up. Elimination diet trials are required for patients with perennial pruritus and/or concurrent gastrointestinal signs. Once a clinical diagnosis of canine AD is made, allergy testing can be performed to identify potential causative allergens for allergen-specific immunotherapy.
第1步-考虑跳蚤感染的可能性 Step 1 – Consider the possibility of fleas 虽然犬感染跳蚤的临床症状多种多样，但与跳蚤叮咬过敏性皮炎（FAD）有关的局部瘙痒性皮肤病变常见部位有腰骶部区域、尾根部和双侧腿前部（图1）。跳蚤感染与跳蚤数量增加有关，但在犬FAD病例中并非如此。此外，临床医生必须意识到许多异位性皮炎患犬可能同时患有FAD，这可能使临床诊断复杂化。 While the clinical signs in a dog with flea infestation are variable, the location of skin lesions and pruritus associated with flea allergy dermatitis (FAD) are most commonly found at the lumbosacral area, tail base and caudomedial thighs (Fig. 1). A flea infestation is associated with increased flea counts, whereas in dogs with FAD this may not be the case. In addition, clinicians must be aware that many atopic dogs may suffer from concurrent FAD, which may complicate the clinical diagnosis. 具体来说，一例瘙痒性病例，为了排除FAD或跳蚤感染的潜在病因，临床医师应该遵循以下几点： To exclude FAD or flea infestation as a possible cause of pruritus in a particular case, clinicians should apply the following guidelines： ● 跳蚤感染以及与跳蚤有关的过敏反应的发病率取决于动物的生活地区。在亚热带和热带气候区域，跳蚤感染问题全年存在，在温带气候区域季节性存在，在干旱、高海拔或寒冷气候区域几乎不存在。即使认为一些特殊地区没有跳蚤，临床医生也应该考虑是否近期有到跳蚤流行地区旅行史，或与来自这些地区的动物接触史。 ● The prevalence of fleas and associated hypersensitivities depends on the geographical area in which the animal lives. Fleas can be a perennial problem in subtropical and tropical climate zones, seasonal in more tempered climate zones and practically non-existent in arid, high elevation, or cold climates. Even if fleas are considered to be absent from a particular area, clinicians should consider any recent travel history to flea endemic areas or contact with animals from such areas. ●对于瘙痒性和/或机体的病变部位不是跳蚤感染主要部位（例如：爪部或耳道）的犬，FAD可能并不是瘙痒的唯一病因。 ● In dogs with pruritus and/or lesions in areas of the body that are not primarily affected by fleas (e.g., the paws or ear canals), FAD may not be the sole cause of pruritus. ●临床医生应对所有瘙痒犬进行直接检查或被毛梳理（跳蚤梳）检查跳蚤或跳蚤粪便。当没有发现跳蚤或跳蚤粪便时为了排除FAD，需要采取一套有效的跳蚤控制方法。临床医生应该知道现有的防跳蚤药物都没有有效的驱避效果，这是因为跳蚤在蛹的阶段能存活174天。在跳蚤流行地区，建议根据其存在时间，始终保持跳蚤的预防。也建议使用快速起效的全身杀虫药，因为与其他局部使用的驱跳蚤药相比，这能更有效地减少瘙痒。 ● Clinicians should check all pruritic dogs for fleas or flea faeces on direct examination or brushing the hair coat (flea combing). To exclude FAD when fleas or flea faeces cannot be found, an effective flea control program should be initiated. Clinicians should be aware that none of the current flea preventatives have an effective repellent effect, and that the fleas in the pupal stage can survive up to 174 days. Based on duration of survival it is recommended to maintain consistent flea prevention in flea endemic areas. It is also advised that fast-acting systemic adulticides are used as these may be more effective at reducing pruritus quickly compared to other topically applied flea preventatives. ●犬AD研究招募的病例，应在研究登记前进行有效跳蚤管控。因为在进入研究前，管理跳蚤可能会影响一些试验结果，近期有研究表明在研究登记前，犬应该进行3个月的跳蚤防控。此外，家中所有其他的犬猫也都需要进行有效的跳蚤防控。 ● Cases that are being entered into a study of canine AD should undergo effective flea control prior to study enrollment. Because the duration of flea control, prior to study inclusion, may influence the outcome of such trials, a recent study suggests that dogs should be on flea prevention for at least 3 months prior to study enrollment. In addition, all other dogs and cats in the household need to be on effective flea control as well. 第2步-考虑其他外寄生虫感染可能性 Step 2 – Consider the possibility of other ectoparasites 除了跳蚤以外，其他体外寄生虫（例如：疥螨、姬螯螨、虱子、恙螨、耳螨）也可能与瘙痒有关，或可能作为并发疾病被发现（例如：蠕形螨病）。虽然大多数寄生虫有特殊易感部位（图2、3、4、5和6），但是在临床上很难进行区分。 Besides fleas, other ectoparasites may be associated with pruritus (e.g., sarcoptic mange, cheyletiellosis, pediculosis, trombiculiasis, otoacariasis) or can be found as a concurrent disease (e.g., demodicosis). Although the majority of these parasites favour specific body areas (Figs. 2, 3, 4, 5 and 6), they can be difficult to distinguish clinically. 在进行过敏原调查之前，应尽可能排除潜在的外寄生虫性皮肤病。可使用多种采样方法进行采样，如皮肤刮片、被毛梳理、拔毛镜检、耳拭子和透明胶带粘贴法。在显微镜下，用低倍物镜（4倍或10倍）和暗光源检查这些寄生虫。下列采样方法可有效用于各种体外寄生虫： Prior to an allergy investigation, every attempt should be made to rule out potential ectoparasitic skin diseases. Various sampling methods such as skin scraping, hair combing, hair plucking, ear swabbing, and acetate tape impressions can be used to collect specimens. For the identification of these parasites a microscopic examination with a low-power objective (4× or 10×) and low light intensity should be used. The following list indicates which sampling methods are effectively used for various ectoparasites: ●犬疥螨：多处皮肤浅刮进行显微镜检，以及可使用血清学试验（间接酶联免疫吸附试验（ELISA））。疥螨在皮肤活检和粪便漂浮法中偶见。 ● Sarcoptes scabiei var. canis: Microscopic examination of multiple superficial skin scrapings, and, where available, blood serum for serology testing (indirect Enzyme-Linked ImmunoSorbent Assay (ELISA). Sarcoptes mites can occasionally be found on skin biopsies and fecal flotation. ●蠕形螨：多处皮肤深刮和挤压皮肤用透明胶带粘贴显微镜检以及拔毛镜检。如果对多处病变部位进行采样，很容易发现蠕形螨。但是对爪部病变或皮肤厚的品种进行采样，可能不总是有效，因此有时需要进行皮肤活检。 ● Demodex spp.: Microscopic examination of multiple deep skin scrapings and acetate tape impressions of “squeezed” skin, and hair pluckings. Usually Demodex mites are easy to find if multiple affected body areas are sampled. However, sampling infected feet or in breeds with thick skin (e.g., shar peis) may not always be effective and skin biopsies may sometimes be required. ●姬螯螨、恙螨（恙螨）和虱子：梳理被毛、透明胶带粘贴和皮肤浅刮进行显微镜检。姬螯螨和虱子也产卵，卵位于毛干且通过镜检能确认。 ● Cheyletiella spp., Trombicula spp. (chiggers), and lice: Microscopic examination of coat brushings, acetate tape impressions and superficial skin scrapings . Cheyletiella spp. and lice also produce eggs, which are attached to hair shafts and can be identified by trichography. ●耳螨：显微镜下检查耳道分泌物。分泌物通常表现为深棕色且易碎（咖啡渣样），螨虫是白色的、快速移动且怕光。偶尔能在身体其他部位皮肤浅刮样本中发现耳螨。 ● Otodectes cynotis: Microscopic examination of aural discharge. The discharge often appears dark brownblack and crumbly (coffee ground-like) and the mites are white, very mobile and light shy. Occasionally ear mites can be found on superficial skin scrapings at other body sites. 犬疥螨和姬螯螨很难发现。因此可能需要经验性驱虫治疗来排除这些寄生虫（例如：塞拉菌素、莫昔克丁、伊维菌素、双甲脒、石硫合剂）。耳廓抓挠反射阳性可能与疥螨有关，需要经验性治疗诊断。特别是在过敏试验中，疥螨可能与室内尘螨发生交叉反应，强烈建议对严重瘙痒的病例进行经验性治疗。 Sarcoptes scabiei var. canis and Cheyletiella spp. can be difficult to find. For this reason a response to an antiparasitic trial treatment (e.g., selamectin, moxidectin, ivermectin, amitraz, lime sulfur) may be necessary to rule out these parasites. A positive pinnal pedal reflex has been associated with Sarcoptes and justifies trial therapy. Especially in the light that Sarcoptic mites are able to cross-react with house dust mites (HDM) in allergy testing, a trial treatment in very pruritic patients is strongly recommended. 第3步-考虑葡萄球菌感染和马拉色菌过度增殖的可能性 Step 3 – Consider the possibility of Staphylococcal infection and Malassezia overgrowth 脓皮病 Pyoderma 由假中间型葡萄球菌（SP）感染引起的细菌性皮肤病在犬AD中很常见。浅表性脓皮病的典型病变表现，如出现脓疱性丘疹和表皮环，常具有明显的特征性，仅凭肉眼就可做出临床诊断。但是，最初确诊应该通过对从皮肤上直接压片或用透明胶带粘贴下的样本，进行Diff-Quik染色，随后进行细胞学检查。穿刺脓疱进行采样最有可能得到明确结果，而从丘疹或表皮环进行采样有价值的结果可能较少。并不是每一个病例的需氧菌培养和药敏试验都能得到明确结果，但是如果满足特定条件的话（例如：有抗生素治疗病史、最初选用的抗生素治疗无效、该地区耐甲氧西林SP发病率高），应该进行细菌培养以明确抗菌谱。当犬正在接受全身抗生素治疗时，可进行细菌培养。 Bacterial skin infections caused by Staphylococcus pseudintermedius (SP) are common in dogs with AD. The typical lesions of superficial pyoderma, such as papulopustular eruption and epidermal collarettes, are often distinctive enough to make a clinical diagnosis on gross appearance alone. However, the initial diagnosis should be confirmed by examining cytological samples, stained with Diff-Quik®, taken from the skin by impression smears or acetate tape impressions. Samples from pricked pustules will most likely yield definitive results, while samples from papules and epidermal collarettes may be less rewarding. Aerobic bacterial culture and sensitivity testing is not indicated in every case, but if particular conditions are fulfilled (e.g., previous history of antibiotic treatment, initial appropriate antibacterial treatment has not been effective, high prevalence of meticillinresistant SP in the area, etc.), a bacterial culture with antibiogram should be performed. Bacterial cultures can be performed while the dog is currently being treated with systemic antibiotics. 葡萄球菌性脓皮病在大多是情况下是继发问题，与潜在的瘙痒性和非瘙痒性疾病有关，如犬AD，但也与其他过敏症和内分泌疾病有关。脓皮病经常导致瘙痒总体水平或分布模式发生改变。在这些情况下，排除脓皮病可确定原发病是否是瘙痒本身，并且明确其严重程度和可能的分布模式。除了典型脓皮病病变表现以外，AD患犬会出现细菌过度增殖，这会使其他病变类型变得复杂化。因此，明智的做法是对多种病灶进行采样，以确定细菌感染程度，并适当控制感染。当病例对“抗过敏”治疗无效时，或是正在进行犬AD研究时，一定要这样检查。 Staphylococcal pyoderma is in most cases a secondary problem associated with underlying pruritic and nonpruritic diseases such as canine AD, but also other allergies as well as endocrinopathies. The pyoderma often causes a change in the overall level or distribution pattern of the pruritus. In these cases, eliminating the pyoderma will determine if the primary disease is itself pruritic, and what its severity and distribution pattern may be. In addition to typical pyoderma lesions, dogs with AD can develop bacterial overgrowth that can complicate other lesion types. Hence, it is wise to sample a variety of lesions to characterise the extent of bacterial involvement and manage the infection appropriately. This should certainly be done whenever cases are poorly responsive to “anti-allergy” therapies, or if studies on canine AD are being performed. 马拉色菌性皮炎 Malassezia dermatitis 鉴别马拉色菌最有效的诊断试验是在皮肤皱褶、皮肤苔藓化和有油性皮脂溢的部位采样，进行细胞学检查（图7）。厚皮马拉色菌是出芽酵母菌（直径3-5μm），外形特征是椭圆形、花生或“俄罗斯套娃”形状，很容易识别。一般来说，临床症状结合细胞学检查发现酵母菌，表明是酵母菌过度增殖或感染。但是，对于犬的马拉色菌超敏反应，仅需极少微生物即可引起瘙痒和相关病变。因此，诊断马拉色菌性皮炎应基于临床症状和细胞学检查结果，并通过对抗真菌的治疗效果得以确认。也可进行真菌培养，但是因为有假阴性培养结果的报道，所以该方法不能用于马拉色菌性皮炎的常规诊断。因此在犬AD的研究中，出现任何数量的马拉色菌，都应进行经验性治疗，以判断是否是少量马拉色菌导致了犬的瘙痒。 The most effective diagnostic test for the identification of Malassezia organisms is skin cytology from affected areas such as skin folds, areas with lichenification and oily seborrhea (Fig. 7). Malassezia pachydermatis is a budding yeast organism (3–5 μm in diameter) with a characteristic oval, peanut or “Russian doll” shape, allowing easy identification. In general, clinical signs associated with the cytological presence of yeasts reflect a yeast overgrowth or infection. However, in dogs with Malassezia hypersensitivity, few organisms may elicit pruritus and associated skin lesions. For this reason a diagnosis of Malassezia dermatitis should be based on the clinical and cytological findings and confirmed by a response to antifungal therapy. Fungal culturing can be performed as well, but is not used routinely for the diagnosis of Malassezia dermatitis, because false negative culture results have been reported. Therefore, in studies of canine AD, the presence of any number of Malassezia organisms should warrant a trial therapy to determine what role, if any, low numbers of Malassezia are playing in causing the dog’s pruritus. 第4步-考虑皮肤食物副反应（CAFR） Step 4 – Consider the role of cutaneous adverse food reaction (CAFR) 与食物有关的瘙痒可能由两种不同的机制引发，一种是非免疫介导反应（食物不耐受），另一种是免疫介导反应，包括IgE介导的过敏反应（食物过敏）。因为对食物成分的反应可有与犬AD一样的临床表现，或作为加重犬AD的诱因，因此CAFR的犬在临床表现上可能与犬AD难以区分。出现胃肠道症状，如腹泻、呕吐、里急后重、软便、胃肠胀气和肠蠕动次数增加的情况，更常见于食物诱导型犬AD。在所有全年都有临床症状的犬AD病例中，CAFR只能通过严格有效的食物排除试验进行排除，而目前还没有合适的商品化的诊断试验。这在治疗犬AD的药物评估试验中尤为重要，因为像糖皮质激素这类药物对食物诱导型AD效果不佳。不幸的是，没有一种日粮被证明对所有CAFR病例都有效。因此，在某些情况下，尤其是出现胃肠道症状时，可能需要进行多次不同的食物试验，直到临床症状完全得到控制。 Food related pruritus can be caused by two different mechanisms, one a non-immune mediated reaction (food intolerance), the other immune mediated which includes IgE-mediated hypersensitivity (food allergy). Because reactions to food components can present clinically as canine AD, or serve as a flare factor in canine AD, dogs with CAFR may be indistinguishable clinically from canine AD. The presence of gastrointestinal signs, such as diarrhoea, vomiting, tenesmus, soft stools, flatulence, and increased number of bowel movements is more typically seen with food-induced canine AD. In any canine AD case that has year-round clinical signs, CAFR can only be ruled out by effective strict elimination diet trials, since accurate diagnostic commercial tests are not currently available. This is especially important in trials evaluating drugs for the treatment of canine AD since food-induced AD may not respond well to those drugs, as shown for corticosteroids. Unfortunately, there are no diets that have been shown to be effective in all cases of CAFR. Therefore in some cases, especially when gastrointestinal signs are present, multiple different diet trials may be needed until a sufficient control of the clinical signs has been achieved. 理想情况下，食物排除试验应该选择犬从未接触过的一种食物成分。不幸的是，大多数可购买的商品日粮包含的食物成分和配料很广泛，很难选择一款合适的食物。大多数非处方日粮和有些单一处方日粮可能会被其他食物成分污染。虽然市场上有水解日粮可以作为备选，但其蛋白质来源是鸡肉或大豆。因此，一些对鸡肉和/或大豆过敏的犬不能使用这样的日粮。犬最常见的食物过敏原是：牛肉、乳制品、鸡肉制品和小麦，较少见的过敏原如大豆、羊肉、猪肉、鱼和玉米。 Ideally an elimination diet trial should be performed with a diet to which ingredients the dog has never been exposed before. Unfortunately, most commercially available diets contain a wide range of ingredients and byproducts, making the selection of an appropriate diet difficult. Most over the counter diets as well as some prescription elimination diets may be contaminated with traces of other food components. Although hydrolysed diets are offered as an alternative option, the protein source is based on either chicken or soy. For this reason some dogs allergic to chicken and/or soy may not respond to such diets [36]. The most common food allergens in dogs are: beef, dairy, chicken products and wheat, and to a lower degree soy, lamb, pork, fish, and corn. 食物试验是进行严格的食物管理，包括商品化或家庭自制的新奇蛋白（例如：兔肉、袋鼠肉、鹿肉、马肉等），或水解蛋白成分。这些新奇蛋白的使用带来了更多的问题，因为其中几种新奇蛋白现在也包含在能买到的商品粮中。一项人医研究也表明，在体外实验中，鹿肉与牛肉IgG存在交叉反应，而另一项研究报告表明，高达85%的食物过敏患犬可能对鹿肉有副反应。在大多数情况下，所有严格的食物排除试验都应该至少单独饲喂8周，已达临床症状完全缓解。如果病情好转，应继续饮食管理，以确定临床症状是否完全缓解或是仅部分缓解。如果一只犬对商品化单一蛋白日粮没有效果，应再次尝试使用家庭自制食物。如果制作得当，家庭自制食物被认为是成分限制最严格的食物。所有食物应该持续饲喂，直到兽医师检查该犬。这点很重要，因为有些犬主人可能没有注意到犬的某些反应，或当犬的症状改善时病变仍存在。如果再重新饲喂以前的食物时，临床症状复发则确诊与食物有关。临床医生应该知道，主人/病犬依从性不良是一个常见的问题。在食物排除试验中，最具代表性的误区是：饲喂餐桌上的食物、生肉皮、零食、将药藏在食物中、使用带风味剂的牙膏、带胶囊的药、带风味剂的药物（例如：非甾体抗炎药、抗生素、防心丝虫或跳蚤的咀嚼片），以及犬吃其他动物的粪便。主人需要知道摄入非常少量的其他食物或食物添加剂，即便是间断性的，也会干扰疗效。地板上的面包屑，甚至是舔另一只犬的空碗都可能会破坏结果。主人的工作是确保犬只吃规定的食物和清水。 A diet trial is performed by instituting a strict trial with a diet containing commercial or home-cooked novel (e.g., rabbit, kangaroo, venison, horse, etc.) or hydrolysed protein ingredients. The use of these novel proteins is becoming more problematic because several of these novel proteins are now available in over the counter commercial diets. A study in humans has also shown that venison does cross-react in vitro with bovine IgG, while another study reported that up to 85 % of food allergic dogs may adversely react to venison. Any strict elimination diet trial should be fed exclusively for a minimum of 8 weeks to achieve complete clinical remission in most cases. If the condition improves, the diet should be continued to determine if there is complete or only partial control of the clinical signs. If a dog is not responding to a commercial elimination diet a second attempt with a home-cooked diet should be performed. Home-cooked diets are considered the most limited ingredient diets if done properly. All diet trials should be continued until the veterinarian examines the dog. This is important as some owners may not recognize a partial response or be aware of lesions still present when a dog appears to have improved. Dietary involvement is confirmed if there is a relapse of clinical disease when the original diet is re-introduced. Clinicians should be aware that poor owner/patient compliance is a common problem. Typical pitfalls during a diet trial are: feeding table food, raw hides, treats, “hiding” medication in food, using flavoured tooth paste, giving medication in gelatine capsules, using flavoured drugs (e.g., NSAIDs, antibiotics, chewable heartworm or flea preventative), and dogs eating other animals’ faeces. Clients need to realize that very small amounts of other foods or food additives ingested, even intermittently, can prevent a favourable response. Crumbs on the floor and even licking another pet’s empty bowl may result in a poor outcome. The client’s job is to make sure the dog ingests nothing but the prescribed diet and water. 一旦完成第1-4步诊断工作，如果瘙痒依旧存在，则临床上可确诊为犬AD。 Once steps 1–4 of the diagnostic work-up has been completed, a clinical diagnosis of canine AD should be considered if the pruritus is still present. 仔细判读犬AD病例的病史和临床表现 Detailed interpretation of the historical and clinical features of canine AD 犬AD的最初临床表现为瘙痒，包括抓挠、摩擦、咀嚼、过度梳理或舔毛、坐地蹭肛门和/或甩头。瘙痒可能有季节性（如：花粉），也可能非季节性（如：尘螨、食物），这取决于所涉及的过敏原。起初瘙痒可能无病变表现，或表现为原发性皮肤病变，如红斑和偶见丘疹（表2）。面部、耳廓凹面、腹部、腋下、腹股沟处、会阴部和四肢远端，是犬AD最常见发病部位（图8），但已发现犬AD发病部位的变化与品种差异有关（表3、图9）。更多的慢性阶段，由于自我损伤、慢性炎症反应和继发感染，会有继发性皮肤病变表现（表2）。典型的继发性皮肤病变表现有抓痕、脱毛、苔藓化、色素沉着、结痂和皮脂溢（图10a-c）。 The initial clinical feature of canine AD is pruritus, which can include scratching, rubbing, chewing, excessive grooming or licking, scooting, and/or head shaking. Depending on the allergens involved, the pruritus may be seasonal (e.g., pollen) or non-seasonal (e.g., dust mites, food). At the beginning the pruritus may be alesional or associated with primary skin lesions such as erythema and occasionally papules (Table 2). The face, concave aspect of the ear pinnae, ventrum, axillae, inguinal area, perineal area and distal extremities are most commonly affected in canine AD (Fig. 8), but breed associated variations of body sites affected by canine AD have been identified (Table 3, Fig. 9). In more chronic stages secondary skin lesions (Table 2) will occur due to self-trauma, chronic inflammation and secondary infections. Typical secondary skin lesions are excoriations, alopecia, lichenification, hyperpigmentation, crusting, and seborrhea (Fig. 10a-c). 当面对一只瘙痒犬时，一种能帮助判读临床症状的新型工具，即临床应用标准，称为“Favrot’s 准则”（表4）。这些是由大量确诊为犬AD的病例总结制定的一套标准。应用复杂的统计分析法，归纳出一组与犬AD关系最密切的临床表现。分析法得出两套标准，在敏感性和特异性方面程度不同。临床医生可根据需求随意选用。例如，使用一套特异性最高的标准，更能确诊出某个特定病例是犬AD。但是，这套标准会漏检掉一些患此病的瘙痒犬。一套敏感性最高的标准更能捕捉犬AD病例，但可能会把其他疾病的犬归为异位性皮炎，而实际上它们并不是。关于应用这些标准的进一步指导详见表4. A new tool to assist with the interpretation of the clinical findings when confronted with a pruritic dog is application of clinical criteria known as “Favrot’s criteria” (Table 4). These include a set of criteria that have been developed from a large case series of confirmed cases of canine AD. The use of complex statistical analysis allowed a set of clinical features to be identified that had maximum association with canine AD. The analysis revealed two sets of criteria, which yield varying levels of sensitivity and specificity for the condition. Clinicians can use whichever set best serves their needs. For example, use of a set of criteria that yields the highest specificity is more likely to ensure that a particular case actually has canine AD. However, this set would exclude some pruritic dogs that were suffering from the disease. A set yielding the highest sensitivity is more likely to capture cases of canine AD, but it could allow some dogs with other conditions to be classified as atopic when in fact they were not. Further guidance about application of these criteria sets is shown in Table 4. 重点要记住，这些标准不应该作为犬AD的“诊断性测试”单独使用。它们应与本文概述的其他方法一起使用。也就是说，如果犬已按上文所述经过详细检查，那使用这些标准时准确性将会显著提高。 It is crucial to remember that these criteria should not be used in isolation as a “diagnostic test” for canine AD. They should be applied alongside the other guidelines outlined in this review. In other words, the accuracy of using these criteria will be greatly enhanced if the dog has been subjected to a careful work-up as described in the previous section. 过敏原检测 Allergy testing 一旦临床上确诊了犬AD，几种因素将会决定是否需要进行过敏原检测。严重的临床症状，每年临床症状持续时间超过3个月，并且因为使用的药物副作用和/或主人依从性差，导致对症治疗效果不佳，大多数情况可以进行过敏源检测。可使用IDT和ASIS。这两种检测都不推荐作为筛查试验，应该只用于证实犬AD的临床诊断。根据检测结果可确定过敏原，从而制定过敏原特异性免疫疗法（ASIT）。虽然IDT会被皮肤科医生作为首选的诊断方法，但与比IDT相比，ASIS具有一些优势，如：病畜无风险（无需镇静）、创伤小（无需重复注射）、更方便（无需剃毛、耗时短）以及药物干扰试验结果风险更低（可同时进行抗炎/止痒治疗）。但是，ASIS只针对血液中的过敏原特异性IgE进行测量，不能顾及其他过敏途径，并且无过敏症的犬经常会有阳性反应结果。 Once a clinical diagnosis of canine AD has been made several factors may play a role in the decision-making whether an allergy test is necessary or not. Severe clinical signs, duration of clinical signs for more than 3 months per year, and insufficient management with symptomatic therapy, due to side effects to the drugs used and/or poor owner compliance, justify in most cases allergy testing. These can be performed by IDT and ASIS. Both tests are not recommended as screening tests and should only be used to confirm the clinical diagnosis of canine AD. The results of these tests are also used to identify the offending allergen(s) in order to formulate an allergen-specific immunotherapy (ASIT). Although IDT is considered the preferred diagnostic method among dermatologists, ASIS has several advantages over IDT, such as: no patient risk (no sedation required), less traumatic (no repeated injection required), more convenient (no clipping needed, less time consuming), and lower risk of drugs interfering with test results (concurrent anti-inflammatory/antipruritic therapy). However, ASIS only measures circulating allergen-specific IgE, does not take into account other allergic pathways and often shows positive reactions in non-allergic dogs. 始终没有标准化的IDT和ASIS，并且怀疑会出现假阳性和假阴性结果。根据评估临床确诊的犬AD中10-30%的犬可能出现IDT阴性。假阴性结果比例这么高可能是由于多个因素造成，包括技术操作不当、过敏原浓度太低、药物干扰、宿主自身因素、过敏原选择不正确、IDT测试时间太长（>60天）或处于过敏症季节的高峰，以及存在异位样皮炎的情况。 IDT and ASIS are still lacking standardization and it is suspected that false positive and false negative results do occur. It is estimated that between 10 and 30 % of dogs with a clinically confirmed canine AD may show a negative IDT. This high percentage of false negative results can be due to several factors including improper technique, too low test concentration of allergens, drug interference, intrinsic host factors, incorrect selection of allergens, IDT performed too long after (>60 days) or during the peak allergy season, and presence of a condition called atopic-like dermatitis. 犬异位样皮炎疾病在临床症状上与犬AD相同，但是测不到对环境或其他过敏原反应的IgE。然而，最近一项研究中表明这种情况与淋巴细胞介导的食物反应有关。虽然已知人的年龄和季节会影响ASIS，但这一信息在犬尚未得到证实。 Canine atopic-like disease is clinically identical to canine AD, but IgE response to environmental or other allergens cannot be documented. However, in a recent study the condition has been associated with a lymphocyte-mediated reaction to food. Although it is well known that in people age and season may influence ASIS, this information has not been well established in dogs. 两种检测方法差异很大，且未标准化，必然导致两者检测结果的相关性较差。尽管如此，基于ASIS和IDT的ASIT的成功率比较无显著差异。最后重点要记住，虽然信息很少，但相关过敏原之间的交叉反应已有报道，例如尘螨和储存螨。基于这一点，重点是要确定一只犬是否真的接触了过敏原并且也发生了反应。结合病史调查和临床表现，对测试结果进行正确解读是很复杂的并且很费时。因此，建议转诊给兽医皮肤专科医生。 Both testing methods are very different and not standardized, which inevitably results in poor correlation between both tests. Nonetheless the success rate of ASIT based on ASIS vs. IDT is not significantly different. Finally, it is important to remember that, although little information is available, cross-reactions between related allergens, e.g., house dust and storage mites, have been reported. Based on this problem it is important to determine if a dog is really exposed to the allergen(s) it reacted too. The proper interpretation of these test results, in conjunction with the clinical history and clinical presentation, can be complex and time-consuming. For this reason a referral to a veterinary dermatologist is recommended. 皮内试验 Intradermal testing IDT是一种因为存在IgE而对皮肤的肥大细胞反应性进行间接测量的方法。选择合适的过敏原进行测试是获得可靠IDT结果的基础。事实上，过敏原以花粉为主，受地理变化影响差异很大。因此，对操作IDT的兽医来说，明确病患生活环境中存在的过敏原非常重要。过敏原的相关信息可以通过联系兽医皮肤专科医生、兽医和医学院、过敏原实验室、教科书、当地人医过敏症专科医生、气象局和国家过敏局(http://www.worldallergy.org/pollen/)获得。应对IDT整体结果不断进行评估，并将无反应的过敏原替换成其他重要过敏原。也可调整皮内试验浓度，因为随着时间延长，建议采用不同的试验浓度（表5）。 IDT is an indirect measure of cutaneous mast cell reactivity due to the presence of IgE. The appropriate selection of allergens to test is fundamental to obtain reliable IDT results. In fact, allergens, mainly pollens, are subject to a great geographic variability. Thus, it is important for veterinarians performing IDT to identify the allergens present in the regional location where the patients live. Information about relevant allergens can be obtained by contacting veterinary dermatologists, veterinary and medical schools, allergy laboratories, textbooks, local human allergists, weather bureau as well as National Allergy Bureau (http://www.worldallergy.org/pollen/). From time to time the overall IDT results should be assessed and allergens, which do not exhibit a reaction may be replaced with other important allergens. Intradermal test concentration may also be adjusted since different test concentrations have been suggested over time (Table 5). 过敏原稀释后相对稳定，且能在玻璃瓶中储存8周，在4 °C环境中在塑料注射器内储存可长达2周。IDT操作前提前先从冰箱内取出测试溶液，放置达到室温。如前所述，应根据特定地区的流行程度选择要测试的过敏原。但是，检测过敏原的选择通常基于个人偏好和经验，即使在同一地区，皮肤专科医生之间的选择也会明显不同。 Allergens are relatively stable once diluted and can be stored in glass vials up to 8 weeks and in plastic syringes for up to 2 weeks at 4 °C. The test solutions should be removed from the refrigerator just prior to the IDT long enough to reach room temperature. As mentioned before the selection of test allergens should be made based on the prevalence of the allergens in a specific geographical region. However, the selection of test allergens is often based on personal preference and experience and can vary significantly among dermatologists even within the same geographical region. 最常用于IDT的皮内注射部位是胸腔侧面，轻柔剃毛并标记注射部位（至少间隔2cm）后进行。通常情况下，每个试验浓度皮内注射0.05-0.1ml，15-20分钟后进行评估。每个注射部位的反应与阳性（磷酸组胺）和阴性（含苯酚的生理盐水）对照组进行比较。对反应进行主观和/或客观判读。主观评估是对红斑、肿胀和/或形成的风疹块的强度和/或大小进行评估，而客观评估是测量红斑或形成的风疹块面积的平均直径。但是，对比两种评估方法未见明显差异。按照惯例，当形成的风疹块至少等于或大于阴性和阳性对照组的反应的中间值时，则过敏原反应呈阳性。如果使用主观评估，阳性对照组一般为4级，阴性对照组为0级。如果过敏原反应为2级或更高，则是为阳性。 Intradermal injections for IDT are most commonly performed on the lateral thorax, after the hair has been gently clipped and the injection sites marked (minimum 2 cm apart). Typically a volume of 0.05– 0.1 ml of each test concentration is injected intradermally and evaluated after 15–20 min. The reaction at each injection site will be compared between those of the positive (histamine phosphate) and negative (saline with phenol) controls. The reaction can be read subjectively and/or objectively. In the first case, assessment of the intensity and/or size of the erythema, turgidity and/or wheal formation will be considered, while for the objective evaluation, measurement of mean diameter of the area of erythema or wheal formation is measured. However, no significant differences were seen where the two methodologies have been compared with each other. By convention, an allergen reaction is positive when the wheal formed is at least equal or greater than halfway between the negative and the positive control reaction. If the subjective evaluation is used, the positive control will assume a conventional grade of 4, whereas the negative control will be graded as 0. A reaction to an allergen is considered positive if it’s graded as 2 or greater. 许多阳性对照已被用于犬IDT测试，其中最可靠的是磷酸组胺。在欧洲，组胺的使用剂量为1:10,000 w/v (0.1 mg/mL)，在美国为1:100,000 w/v (0.01 mg/mL)，但是，也有人提出，溶液浓度更高可能会产生更一致的阳性皮肤反应。阴性对照应包括用于稀释IDT过敏原的溶液，通常是用含苯酚的无菌生理盐水作为防腐剂。 Many positive controls have been tested for IDT in dogs; of those the most reliable is histamine phosphate. Histamine has been used at 1:10,000 w/v (0.1 mg/mL) in Europe and 1:100,000 w/v (0.01 mg/mL) in the USA; nevertheless it has been suggested that the more concentrated solution (1:10,000) may yield a more consistent positive skin reaction. The negative control should consist of the solution, which is used to dilute the allergens for the IDT; this is generally sterile saline with phenol as preservative. 过敏原特异性IgE血清学试验 Allergen-specific IgE serology testing 以固相ELISA为基础的几种试验方法，在人医和兽医已用于血清IgE的检测。这些方法用于针对一组与病例有关的过敏原（例如：花粉、霉菌、尘螨和皮屑过敏原）特异性IgE抗体的检测。在近20年里，采用单克隆、单克隆混合物或多克隆的抗犬IgE，检测血清IgE。但是，由于单克隆抗体的敏感性和特异性更高，所以多克隆抗犬IgE抗体的使用明显减少。另一名兽医尝试使用人的细胞外部分IgE高亲和力受体α亚基(FcεRIα) 的单一重组片段进行试验，表现出对犬IgE有高亲和力且缺少对IgG的交叉反应。，Allercept E-screen©(Heska Corp, Ft Collins, CO, USA)的两种临床免疫点分析法，已被确定用于犬血清过敏原特异性IgE的检测。这种检测可用于筛选试验，指导兽医使用跳蚤、尘螨和花粉过敏原混合物进行全板ASIS或IDT，确定可能性。Allercept E-screen©免疫点分析法，能大概率预测IDT和/或ASIS是阴性或是阳性。但是，这是一种混合过敏原筛选试验，不允许识别单个过敏原，因此不能完全替代IDT或ASIS检测。目前其他许多公司都提供过敏原特异性血清学检测，但是根据最近的一项研究，实验室之间的检测结果并不一致。 Several assays, mostly based on solid phase ELISAs, have been tested for serum IgE in both human and veterinary medicine. These assays are used to detect specific IgE antibodies against a panel of allergens (e.g., pollen, mould, HDM and epidermal allergens) considered relevant for the patient. In the past decades, the detection of serum IgE has been done using monoclonal, mixed monoclonal or polyclonal anti-canine IgE. However, due to the higher sensitivity and specificity of a monoclonal antibody, the use of polyclonal anti-canine IgE antibodies has decreased markedly. Another veterinary assay using a unique recombinant fragment of the extracellular portion of the human high affinity IgE receptor alpha-subunit (FcεRIα) has shown a strong affinity for canine IgE and a lack of cross-reactivity with IgG. Two versions of in-clinic immunodot assay, Allercept E-screen© (Heska Corp, Ft Collins, CO, USA) has been validated to detect allergen-specific IgE in canine sera. This test has been used as screening test to guide the veterinarian to determine the possibility to perform a full panel ASIS or IDT using mixtures of flea, HDM and pollen allergens. The Allercept E-screen© immunodot assay was able to predict with high probability whether an IDTand/or ASIS would be negative or positive. However, this test is a screening test using mixed allergen, which does not allow the identification of the individual offending allergen, and so does not replace complete IDT or ASIS testing. Currently many other companies are offering allergenspecific serology testing, but based on a recent study test results do not agree well between laboratories.
图9：拳师犬、德国牧羊犬、金毛犬、沙皮犬、大麦町犬、拉布拉多犬、法国斗牛犬、西高地白㹴和杰克犬的异位性皮炎轮廓图（按此顺序排列）。每种颜色对应患病动物百分比。Fig. 9Silhouettes of atopic boxers, German shepherd dog, golden retrievers, shar peis, Dalmations, Labradors retriever, French bulldogs, West Highland white terriers and Jack Russell terriers (in this order). Each colour corresponds to the percentage of affected animals
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