特应性皮炎患犬和异位样皮炎患犬的皮肤统计学数据、疾病严重程度 ...

王帆

Comparison of demographic data, disease severity and response to treatment, between dogs with atopic dermatitis and atopic-like dermatitis: a retrospective study

特应性皮炎患犬和异位样皮炎患犬的皮肤统计学数据、疾病严重程度和治疗反应的比较:一项回顾性研究

Larissa S. Botoni , Sheila M. F. Torres, Sandra N. Koch , Marcos B. Heinemann and Adriane P. Costa-Val

 

翻译：王帆

Abstract

Background – Limited information is available describing the features of canine atopic-like dermatitis (ALD) compared with atopic dermatitis (AD).

Objectives – To compare demographic data, disease severity and response to therapy between ALD and AD dogs.

Animals – Two hundred and fifty-three atopic dogs with intradermal and serum allergen-specific IgE test results were selected retrospectively.

Methods and materials – Dogs were enrolled into the ALD group if both IgE tests were negative and into the AD group if at least one test was positive. Demographic data, pruritus level and number of body sites affected before and during therapy, in addition to maintenance therapy protocols, were compared between groups.

Results – There were 216 (85.38%) dogs in the AD group and 37 (14.62%) in the ALD group. The soft-coated wheaten terrier, American Staffordshire terrier, English bulldog and Labrador retriever were over-represented in the AD group. No significant differences between the groups were noted regarding the other demographic variables evaluated. There were no differences in the mean pruritus scores and number of affected body sites at the first visit or during treatment. Furthermore, no significant differences between the groups were noted for the maintenance treatment scores and reduction of pruritus level and number of body sites affected during treatment.

Conclusions and clinical significance – The soft-coated wheaten terrier, American Staffordshire terrier, English bulldog and Labrador retriever were over-represented in the AD group. No significant differences in the other demographic data and clinical features were noted between dogs with ALD and AD in the present study.

摘要

背景 – 相比于特应性皮炎（AD），对犬异位样皮炎（ALD）特征信息的描述信息有限。

目的 – 比较ALD和AD患犬的数量统计学数据、疾病严重程度和对治疗的反应。

动物 – 回顾性分析了253只特应性疾病患犬的皮内和血清过敏原特异性IgE检测结果。

方法和材料 - 如果两项IgE检测均为阴性，则将犬归入ALD组；如果至少一项检测为阳性，则将其归入AD组。除了维持治疗方案之外，在两组之间比较数量统计学数据、瘙痒水平和治疗之前和期间机体发病部位的数量。

结果 – AD组有216只犬(85.38%)，ALD组有37只犬(14.62%)。在AD组中，大多是软毛小麦㹴、美国斯塔福德郡㹴、英国斗牛犬和拉布拉多猎犬。两组的其它统计学变量方面评估，无显著差异。首次就诊或治疗期间，平均瘙痒评分和发病部位的数目没有差异。此外，两组之间在维持治疗评分、瘙痒水平减少和治疗期间发病的机体部位数量等方面无显著差异。

结论和临床意义 – AD组中，软毛小麦㹴、美国斯塔福德郡㹴、英国斗牛犬和拉布拉多猎犬的比例较高。本研究中，ALD和AD患犬在其它统计资料和临床特征方面无显著差异。

 

Introduction

介绍

In humans, atopic dermatitis (AD) has been traditionally classified into two subtypes according to the level of serum total IgE and the presence of specific IgE against environmental and food allergens. The intrinsic type (IAD), also named nonallergic AD, nonatopic eczema, atopiform dermatitis or nonallergic atopic eczema/dermatitis syndrome, is characterized by low or normal serum total IgE levels and negative allergen-specific IgE reactions to common environmental and food allergens, in the serum and skin prick test. The extrinsic type of AD (EAD) or allergic atopic eczema/AD is characterized by high serum total IgE levels and positive allergen-specific IgE to common environmental and food allergens. It has been hypothesized that IAD and EAD are different stages of AD. The condition in infancy may begin as nonallergic (IAD) and progress to atopy (EAD) overtime. This hypothesis has been supported by two studies that reported allergen sensitization with positive allergen-specific IgE in a number of patients initially diagnosed as IAD.

在人医中，特应性皮炎(AD)传统上根据血清总IgE水平和是否有针对环境和食物过敏原的特异性IgE分为两种亚型。内源性(IAD)，也称为非过敏性AD、非特应性湿疹、异位样皮炎或非过敏性特应性湿疹/皮炎综合征，特征是血清总IgE水平低或正常，在血清和皮肤针刺试验中，常见环境和食物过敏原特异性IgE反应阴性。外源性AD (EAD)或变应性特应性湿疹/AD的特点是血清总IgE水平高，对常见环境和食品过敏原特异性IgE呈阳性。推测AD和EAD是AD的不同阶段。婴儿期的症状可能以非过敏性(IAD)开始，随着时间的推移逐渐发展为特应性(EAD)。这一假设得到了两项研究的支持，这两项研究报告了在一些最初诊断为IAD的患者中，过敏原致敏同时过敏原特异性IgE阳性。

 

Canine atopic-like dermatitis (ALD) has been defined as an inflammatory and pruritic skin disease with clinical features identical to those seen in canine AD, in which an IgE response to environmental or other allergens cannot be documented. Because total serum IgE levels have a poor correlation with the atopic status in dogs, this parameter cannot be used to distinguish AD and ALD in dogs. Thus, in dogs, the differentiation has been made on the basis of the results of intradermal (IDT) and serum allergen-specific IgE tests (AST).

犬异位样皮炎(ALD)被定义为一种炎性和瘙痒性皮肤病，临床特征与犬AD相同，无法测到对环境或其他过敏原IgE。由于血清总IgE水平与犬的特应性疾病相关性较差，该参数不能用于区分犬的AD和ALD。因此，根据皮内(IDT)和血清过敏原特异性IgE测试(AST)的结果，对犬进行了区分。

 

To the best of the authors’ knowledge, there is only one study, published as an abstract, contrasting the clinical and epidemiological features of canine AD versus ALD. Several other studies have investigated different aspects of ALD; however, the diagnosis was made based on either IDT or serum test, not strictly both. The primary aim of this retrospective study was to compare, in a population of dogs diagnosed with AD or ALD using both the IDT and AST tests, the following: (i) demographic data; (ii) disease severity measured by pruritus level, number of body sites affected and treatment and (iii) response to therapy measured by reduction in pruritus level and number of body sites affected during treatment. The secondary aim was to summarize the demographic data of all dogs included in the study.

据作者所知，只有一项研究以摘要形式发表，对犬AD和ALD的临床和流行病学特征进行了对比。然而，诊断是基于IDT或血清测试，而不是严格地同时进行。本回顾性研究的主要目的是比较，在使用IDT和AST测试诊断为AD或ALD的犬病例中，如下:(i)统计学数据;(ii)以瘙痒程度、机体病变部位数目及治疗来衡量疾病的严重程度;(iii)以治疗期间瘙痒程度及机体病变部位数目的减少来衡量治疗的反应。第二个目的是总结所有纳入研究的犬的统计学数据。

 

Methods and materials

方法和材料

Medical record search and data collection

医疗记录搜索和数据采集

Medical records of dogs seen in a veterinary teaching hospital from 2007 to 2015 were searched using the keywords as follows: atopic dermatitis, atopy, allergy, dog and canine. Inclusion criteria for eligible dogs were (i) diagnosis of AD; (ii) IDT and AST test results available, and (iii) IDT and AST tests performed on the same day. Exclusion criteria were (i) dogs with nonseasonal clinical signs of AD with no records of an elimination diet trial performed; and (ii) dogs assigned to the ALD group that had a positive response to a food trial (because this could represent an IgE-mediated allergic response). Data collected from each dog included sex, breed, age of disease onset, seasonality, presence of respiratory signs, presence of conjunctivitis, performance of food trial, food trial response, percentage of time spent indoors, body regions affected, pruritus level and treatment. A standard history questionnaire was part of the electronic medical record (UVIS, Universal Veterinary Information System, Ross Group Inc.; Miamisbur, OH, USA); therefore, the listed information was documented consistently for all cases.

以特应性皮炎(atopic dermatitis)、特应性(atopy)、过敏症(allergy)、犬(dog)、犬(canine)为关键词，对2007年至2015年在某兽医教学医院就诊的犬的病历进行检索。纳入标准为:(1)诊断为AD;(二)有IDT和AST测试结果，(三)同一天进行了IDT和AST测试。排除标准:(i)有非季节性AD临床症状，并且没有进行食物排查试验的记录;(ii) ALD组的犬对食物试验有阳性反应(因为这可能代表IgE介导的过敏反应)。从每只犬收集的数据包括性别、品种、发病年龄、季节性、呼吸症状、结膜炎、食物试验表现、食物试验反应、待在室内的时间百分比、患病机体部位、瘙痒程度和治疗。一份标准的病史问卷是电子病历的一部分(UVIS);因此，所列信息对所有病例进行了一致的记录。

 

Intradermal and serum allergen-specific IgE test protocols

皮内和血清过敏原特异性IgE测试方案

The IDT test was performed by clipping the dog’s lateral thorax and injecting in the dermis 0.1 mL of 60 environmental allergens (Stallergenes Greer; Lenoir, NC, USA). The reactions were evaluated 15 min after the injections and subjectively graded 0 to 4+ based on the negative (saline) and positive (1:100,000 histamine) controls. The dogs were sedated for the test using dexmedetomidine hydrochloride (Orion Corp.; Espoo, Finland) intravenously at the dose of 0.004 mg/kg. Drug withdrawal time prior to IDT was as follows: two weeks for antihistamines, essential fatty acids and topical products containing glucocorticoids, four weeks for oral glucocorticoids, ciclosporin and oclacitinib and, six to eight weeks for injectable glucocorticoids.

患犬胸侧剃毛进行IDT试验，60种环境过敏源(Greer)进行皮内注射0.1毫升。注射后15 min评价反应，根据阴性对照(生理盐水)和阳性对照(1∶10万组胺)主观评分为0 ~ 4+。使用盐酸右美托咪定静脉注射，剂量为0.004 mg/kg。IDT前停药时间如下:抗组胺药、必需脂肪酸和含糖皮质激素的外用药物停2周，口服糖皮质激素、环孢素和奥拉替尼停4周，注射用糖皮质激素停6 ~ 8周。

 

Approximately 3 mL of blood was collected for the AST and placed in serum separator glass tubes. The serum was separated by centrifugation and stored refrigerated under 2–4°C until submission to the laboratory within 12 h of collection. The AST was performed by IDEXX reference laboratories (IDEXX Laboratories, Inc.; Westbrook, MA, USA) using the Greer Aller-g-complete kit (Stallergenes Greer). A monoclonal antibody cocktail-based ELISA was used for the detection of serum allergen-specific IgE, as described previously.

采集约3 mL血液用于AST，置于血清分离机玻璃管中。血清通过离心分离并在2 ~ 4℃下冷藏保存，直至在采集后12 h内提交实验室。AST由IDEXX参考实验室(IDEXX)使用Greer Aller-g-complete试剂盒。如前所述，我们使用基于单克隆抗体鸡尾酒的ELISA检测血清过敏原特异性IgE。

 

The allergen panel used in the IDT and AST included household allergens, moulds and pollens of trees, grasses and weeds (Tables S1 & S2, respectively).

IDT和AST使用的过敏原板包括家庭过敏原、树木、草和杂草的霉菌和花粉(分别见表S1和表S2)。

 

Study population

研究对象

Dogs were placed into the AD or ALD group based on their IDT and AST results. The dogs that did not show any positive reactions on both the IDT and AST were classified as ALD. The ones that showed one or more positive reactions on one or both tests were placed in the AD group. To be considered positive on the IDT, any reaction had to have a 2+ or higher score, and be associated with erythema and skin turgidity.9 To be considered positive on the AST, the reaction had to be ≥80 EAU (ELISA absorbance units) as reported by IDEXX Laboratories.

根据IDT和AST结果将犬分为AD组或ALD组。对IDT和AST均未显示任何阳性反应的犬被归类为ALD。在一项或两项测试中表现出一项或多项阳性反应的人被置于AD组。被认为是阳性的IDT，任何反应必须有2+或更高的评分，并与皮肤发红和皮肤肿胀有关IDEXX实验室报告的AST阳性反应必须≥80 EAU (ELISA吸光度单位)。

 

Statistical analyses

统计分析

All dogs were included in the demographic data analysis. However, for all other analyses, only dogs with at least four follow-up visits were included because this was considered to be a reasonable minimal number of visits necessary to determine the maintenance treatment regimen and evaluate response to therapy. Means and standard deviations were used to report the time period to achieve four follow-up visits, the maximum duration of the follow-up period and the number of follow-up visits.

所有犬均纳入统计学数据分析。然而，在所有其他分析中，仅纳入至少有4次随访的犬，因为这被认为是确定维持治疗方案和评估治疗应答所需的合理最低访视次数。使用均值和标准差报告实现4次随访的时间、随访期间的最长持续时间和随访次数。

 

Descriptive statistics was used to characterize the demographic variables in each group in addition to the groups combined. Means were compared between the AD and ALD groups using the chi-square test or Fisher’s exact test for the qualitative data and the Wilcoxon–Mann–Whitney U-test for the quantitative data. To determine whether there was breed predisposition to develop AD or ALD, breed frequency was compared between each group and the general canine hospital population seen during the study period, using Fisher’s exact test.

除合并组外，采用描述性统计量表征每组的人口统计学变量。采用χ 2检验或Fisher确切概率法对定性资料进行比较，采用Wilcoxon-Mann-Whitney u检验对定量资料进行比较。为了确定是否存在患AD或ALD的犬种易感性，我们比较了各组与研究期间医院普通犬群的犬种频率，使用了Fisher精确检验。

 

In order to assess differences in disease severity, the mean pruritus level and number of body sites affected at the first visit were compared between the AD and ALD groups using the Wilcoxon– Mann–Whitney U-test. In order to standardize the information available in the medical records, the dog’s body surface was divided as follows: face, ears, neck, thorax, dorsum, flanks, abdomen, axillae, groins, front legs, hind legs, front paws, hind paws, perineum and tail. Each of these body sites was counted as one affected area, totalling 16 sites. The pruritus level recorded in the medical records was based on a 0–10 scoring system using owner’s verbal assessment (before 2009) or the pruritus Visual Analog Scale (pVAS) as reported previously (after 2009).

为了评估疾病严重程度的差异，使用Wilcoxon - Mann-Whitney u检验比较了首次就诊时AD组和ALD组的平均瘙痒水平和患病机体部位数量。为规范病历中可获得的信息，将犬体表分为:面、耳、颈、胸、背、胁、腹、腋窝、腹股沟、前腿、后腿、前爪、后爪、会阴和尾巴。每一个机体部位算作一个患病部位，共16个部位。病历中记录的瘙痒水平是基于0 ~ 10分的评分系统，使用宠主的口头评估(2009年之前)或之前报告的瘙痒视觉模拟量表(pVAS)(2009年之后)。

 

The dog’s pruritus level at the first visit also was evaluated by categorizing the scores in severity levels according to the recommendations of the International Committee on Allergic Diseases of Animals (ICADA) as follows: mild: 2.0–3.5; moderate: 3.6–5.5 and severe: 5.6–10). The frequency of each severity score was compared between the groups using Fisher’s exact test. Additionally, to indirectly assess disease severity, the maintenance treatment modalities were scored and compared between the AD and ALD groups using Fisher’s exact test. The following empirical treatment scoring system was developed and used in the analysis: 1 (antihistamines and/or essential fatty acids and/or allergen-specific immunotherapy); 2 [one immunomodulatory agent (i.e. oral glucocorticoid, ciclosporin, oclacitinib or lokivetmab) with or without one or more of the medications included in score 1] and 3 (two or more immunomodulatory drugs, with or without one or more of the medications included in score 1). We considered maintenance treatment to be the most frequently used protocol that controlled the disease and this was determined as the average treatment scores during four or more follow-up visits.

根据国际动物过敏性疾病委员会(ICADA)的建议进行严重程度评分:轻度:2.0 ~ 3.5分;中度:3.6 ~ 5.5，重度:5.6 ~ 10。采用Fisher精确检验比较组间各严重程度评分的频率。此外，为了间接评估疾病严重程度，我们对维持治疗模式进行了评分，并使用Fisher精确检验在AD组和ALD组之间进行了比较。建立了以下经验性治疗评分系统并用于分析:1(抗组胺药和/或必需脂肪酸和/或过敏原特异性免疫治疗);2[一种免疫调节剂(即口服糖皮质激素、环孢素、奥拉替尼或洛基维特单抗)联用或不联用1分中包含的一种或多种药物]和3(两种或多种免疫调节剂联用或不联用1分中包含的一种或多种药物)。我们认为维持治疗是控制疾病的最常用方案，这是在≥4次随访期间的平均治疗评分。

 

In order to assess differences in response to therapy, the mean pruritus scores and mean number of body sites affected during treatment were compared between the ALD and AD groups using the Wilcoxon–Mann–Whitney U-test. The pruritus scores were then categorized in severity levels as described above, and the frequency of each severity score was compared between the groups using Fisher’s exact test. Because there were no significant differences between the groups in the number of dogs in each of the maintenance treatment scores, the analysis was not blocked by treatment scores. The reduction of pruritus scores and number of lesions overtime also were compared between the groups to measure differences in therapy responses using a marginal linear regression model. All statistical analyses were performed using the software R v.3.2.4 (R Core Team. R: A Language and Environment for Statistical Computing. http://www.R-project.org; R Foundation for Statistical Computing, Vienna, Austria, 2014). A P-value ≤0.05 was considered significant.

为了评估治疗反应的差异，使用Wilcoxon-Mann-Whitney u检验比较了ALD组和AD组治疗期间的平均瘙痒评分和患病机体部位的平均数量。然后按照上述严重程度对瘙痒评分进行分类，并使用Fisher精确检验比较各组之间各严重程度评分的出现频率。由于各维持治疗评分中犬的数量在组间无显著差异，因此分析未被治疗评分阻碍。我们还比较了各组随时间推移瘙痒评分和皮损数量的减少情况，以使用边际线性回归模型衡量治疗应答的差异。采用R v.3.2.4软件(R Core Team。R:统计计算的语言和环境。http://www.R-project.org;R基金会统计计算，维也纳，奥地利，2014年)。p值≤0.05被认为是显著的。

 

Results

结果

Demographic data

皮肤学数据

A total of 2,691 cases were initially retrieved, and 253 were considered eligible for the study based on the inclusion and exclusion criteria. Two hundred and sixteen (85.38%) dogs were included in the AD group and 37 (14.62%) in the ALD group. There were no significant differences between the groups in the demographic variables presented in Table 1. The proportion of males (51.4%; 51.4%) and females (48.6%; 48.6%), respectively, in the ALD and AD groups was identical (P = 0.997). There were no significant differences in the age of disease onset (ALD: 16.2 months; AD: 20.9 months; P = 0.232). The respiratory signs recorded in the medical records were sneezing, coughing and running nose. The most common respiratory sign in the ALD and AD groups was sneezing. The proportion of dogs with respiratory signs was low in both groups (ALD: 24.3%; AD: 19.0%; P = 0.317), as was the frequency of dogs with conjunctivitis (ALD: 21.6%; AD: 18.1%; P = 0.648). Clinical signs of AD were predominantly yearround in the ALD and AD groups (70.3%; 60.2%; P = 0.244) and the dogs in each group spent on average>80% of the time indoors (ALD: 87.0%; AD: 83.5%; P = 0.385).

共检索到2 691例患者，根据纳入和排除标准筛选出符合研究条件的患犬253例。AD组216只(85.38%)，ALD组37只(14.62%)。表1所示的统计学变量在组间无显著差异。雄性(51.4%;51.4%)和雌性(48.6%;48.6%)差异无统计学意义(P = 0.997)。两组患犬发病年龄(ALD: 16.2月AD: 20.9月;P = 0.232)。在医疗记录中记录的呼吸症状有打喷嚏、咳嗽和流鼻涕。ALD组和AD组最常见的呼吸症状是打喷嚏。两组犬出现呼吸症状的比例均较低(ALD: 24.3%;AD:19.0%;P = 0.317)，犬结膜炎的发生率也是如此(ALD: 21.6%;AD:18.1%;P = 0.648)。在ALD组和AD组中，AD的临床症状主要集中在全年(70.3%;60.2%;P = 0.244)，每组犬平均80%的时间在室内(ALD: 87.0%;AD:83.5%;P = 0.385)。

 

A strict food elimination diet trial followed by challenge was performed in 222 of 253 dogs (87.7%), and a partial positive response was observed in 25 of 253 dogs (11.3%), all from the AD group. The 31 dogs that did not have a food trial performed (26 AD and 5 ALD) had strictly seasonal clinical signs (Table 1).

对253只犬中的222只(87.7%)进行了严格的食物排查试验，253只犬中有25只(11.3%)出现部分阳性反应，均来自AD组。31只没有进行食物试验的犬(26只AD和5只ALD)有严格的季节性临床症状(表1)。

 

There were 34 of 216 (13.4%) dogs with positive serology and negative intradermal test results in the AD group. When all study dogs were compared to the general hospital population seen during 2007 and 2015, the softcoated wheaten terrier (P<0.000; OR = 5.8), American Staffordshire terrier (P<0.000; OR = 4.76), English bulldog (P=0.005; OR = 3.49) and the Labrador retriever (P=0.037; OR = 1.40) were predisposed to developing AD. Breeds over-represented in the AD group also included the soft-coated wheaten terrier (P<0.001; OR = 5.8), American Staffordshire terrier (P<0.000; OR = 5.61), English bulldog (P=0.002; OR = 4.11) and the Labrador retriever (P=0.024; OR = 1.46). There were no over-represented breeds in the ALD group when compared to the general hospital population seen during the study period.

AD组216只犬中有34只(13.4%)血清学阳性、皮试阴性。将所有研究犬与2007年至2015年全科住院病例的进行比较时，软毛麦㹴(P＜0.000;OR = 5.8)、美国斯塔福德㹴(P＜0.000;OR = 4.76)、英国斗牛犬(P=0.005;OR = 3.49)和拉布拉多寻回犬(P=0.037;OR = 1.40)是AD的易感因素。在AD组中比例过高的品种还包括软毛麦㹴(P＜0.001;OR = 5.8)、美国斯塔福德㹴(P＜0.000;OR = 5.61)、英国斗牛犬(P=0.002;OR = 4.11)和拉布拉多寻回犬(P=0.024;Or = 1.46)。与研究期间所见的全科住院病例相比，ALD组中没有易感品种。

 

For the analyses of disease severity and response to therapy, 171 dogs with records of at least four followup visits were included. The mean time period to achieve four follow-up visits was 5.1 months (SD: 1.7; range: 2–11), and the maximum duration of the followup period was eight years (mean: 3.0 years; SD: 1.9 years; range: four months to eight years). The mean number of follow-up visits was 6.7 (SD: 2.39; range four to 18).

为了分析疾病严重程度和对治疗的反应，171只犬至少有四次随访记录。实现4次随访的平均时间为5.1个月(SD: 1.7;随访范围:2 ~ 11年)，最长随访时间为8年(平均3.0年;SD: 1.9年;范围:四个月至八年)。平均随访次数为6.7次(SD: 2.39;范围从4到18)。

 

Comparison of disease severity between the AD and ALD groups

AD组和ALD组疾病严重程度的比较

The pruritus scores and number of affected body sites of dogs at the first visit and the maintenance therapy protocols across visits were used as parameters to assess disease severity in the groups. There was no significant difference (Wilcoxon–Mann–Whitney U-test, P = 0.433) in the mean pruritus score of dogs in the AD (6.5±2.1; range: 0–10) and ALD (6.87±1.86; range: 2–9) groups (Figure 1a). When pruritus scores were categorized in severity levels, most dogs in the AD (70.4%) and ALD (81.2%) groups had severe pruritus. There were no significant differences between the groups (Fisher’s exact test; P = 0.908) in the frequencies of cases classified as having mild, moderate or severe pruritus levels (Figure 1b).

以首诊时犬瘙痒评分、患病部位数量及每次随访维持治疗方案作为评估各组疾病严重程度的参数。AD组犬的平均瘙痒评分(6.5±2.1;范围:0 ~ 10)和ALD (6.87± 1.86;范围:2-9)组(图1a)。当瘙痒评分按严重程度分类时，AD组(70.4%)和ALD组(81.2%)的大多数犬有重度瘙痒。组间差异无统计学意义(Fisher精确检验;P = 0.908)在分类为轻度、中度或重度瘙痒的病例频率方面(图1b)。

 

There was no significant difference (Wilcoxon–Mann– Whitney U-test; P = 0.474) in the mean number of affected body sites between the AD (3.8±1.8; range: 0– 11) and the ALD (3.7±2.6; range = 0–8) groups (Figure 2).

无显著性差异(Wilcoxon-Mann - Whitney u检验;P = 0.474)， AD (3.8±1.8;范围:0 - 11)和ALD (3.7±2.6;range = 0-8)组(图2)。

 

No significant differences (Fisher’s exact test; P = 0.796) in the frequencies of dogs receiving each of the categorized maintenance treatment modality was noted between the AD and ALD groups (Figure 3).

无显著差异(Fisher精确检验;P = 0.796)，在AD组和ALD组之间，接受每种分类维持治疗方式的犬的频率(图3)。

 

Comparison of response to therapy between the AD and ALD groups

AD组与ALD组治疗反应比较

The pruritus scores and number of affected body sites of the dogs taken across at least four revisits (i.e. during treatment) were used as parameters to assess response to therapy between the groups. There was no significant difference (Wilcoxon–Mann–Whitney Utest; P = 0.949) in the mean pruritus score of the dogs in the AD (4.7±1.4; range: 1.1–10) and ALD (4.7±1.9; range = 2.8–7.1) groups during treatment (Figure 4a). When the pruritus scores were categorized in severity levels, most dogs in the AD (51.6%) and ALD (68.8%) had moderate pruritus. There were no significant differences between the groups (Fisher’s exact test; P = 0.528) in the frequencies of cases classified as having mild, moderate or severe pruritus levels (Figure 4b).

在至少4次复诊(即治疗期间)中，瘙痒评分和患病机体部位的数量被用作评估组间治疗反应的参数。两组间差异无统计学意义(Wilcoxon-Mann-Whitney Utest;P = 0.949)的平均瘙痒评分(4.7±1.4;范围:1.1 ~ 10)和ALD (4.7±1.9;范围= 2.8-7.1)组(图4a)。当瘙痒评分按严重程度分类时，AD组(51.6%)和ALD组(68.8%)的犬均为中度瘙痒。组间差异无统计学意义(Fisher精确检验;P = 0.528)在分类为轻度、中度或重度瘙痒的病例频率方面(图4b)。

 

There was no significant difference (Wilcoxon–Mann– Whitney U-test; P = 0.093) in the mean number of affected body sites between the AD (3.0±1.2; range: 0.4–8.5) and the ALD (3.0±1.4; range = 1–5.8) groups during treatment (Figure 5).

无显著性差异(Wilcoxon-Mann - Whitney u检验;P = 0.093)，平均患病机体部位数在AD (3.0±1.2;范围:0.4-8.5)和ALD (3.0±1.4;范围：1-5.8)组(图5)。

 

No significant difference was noted between the groups in the reduction of pruritus level (marginal linear regression model; P = 0.061) or number of body sites affected (marginal linear regression model; P = 0.365) during treatment.

两组间瘙痒程度的减少无显著差异(边际线性回归模型;P = 0.061)或患病机体部位数量(边际线性回归模型;P = 0.365)。

 

Discussion

讨论

In the present study, ALD comprised 14.62% of the enrolled population. This incidence is lower than a previous report of 25.6% for dogs; by comparison, the reported incidence is 10–45% in humans with IAD. Moreover, in contrast to humans where females appear to be at increased risk for developing both, IAD and EAD, neither our study nor a previous study found a significant difference in sex distribution within the groups. We observed an earlier mean age of onset in ALD dogs compared to AD (16.2 versus 20.9 months);however, this difference was not statistically significant. A previous study reports the mean age of onset to be identical in both groups. In contrast, human patients with IAD are known to have a later disease onset compared to EAD, even though IAD remains more common in children than adults.

在本研究中，ALD占登记数的14.62%。这一发病率低于此前报道的25.6%;相比之下，IAD患者的报告发病率为10-45%。此外，与人类相比，女性患IAD和EAD的风险似乎都更高，无论是我们的研究还是之前的研究都没有发现群体内性别分布有显著差异。我们观察到ALD犬的平均发病年龄早于AD(16.2个月vs . 20.9个月);然而，这一差异没有统计学意义。此前的一项研究报告显示，两组患者的平均发病年龄相同。相比之下，已知IAD患者的发病时间比EAD晚，但IAD在儿童中比成人更常见。

 

In humans, IAD is typically not associated with other atopic diseases, such as asthma, rhino-conjunctivitis and contact dermatitis. No differences were found between the groups regarding the presence of respiratory signs and conjunctivitis, which were infrequent in our canine patients. Conjunctivitis was observed in 18.6% of all enrolled dogs and similar results have been reported elsewhere. In another study, the frequency of allergic conjunctivitis in atopic dogs was 60%, suggesting that conjunctivitis could in fact be underdiagnosed in this disease.

在人医中，IAD通常不与其他特应性疾病相关，如哮喘、鼻结膜炎和接触性皮炎。两组间在呼吸症状和结膜炎的存在方面没有发现差异，而这在我们的犬类患者中并不常见。在所有登记的犬中，有18.6%患有结膜炎，其他地方也报道了类似的结果。在另一项研究中，过敏性结膜炎在特应性皮炎犬中发生的频率为60%，这表明事实上，在这种疾病中，结膜炎可能被低估了。

 

Studies evaluating breed predisposition to AD show marked regional variations, yet the Labrador retriever has been frequently reported in various studies from different locations,so our results are in accordance with previous studies. The other overrepresented breeds in our study were the soft-coated wheaten terrier, English bulldog and American Staffordshire terrier. In one study performed in Australia, the English bulldog and American Staffordshire terrier also were shown to be at increased risk for developing AD; in a worldwide multicentre study, bulldogs (English and French combined) were overrepresented. In addition, one study from Switzerland reported an over-representation of soft-coated wheaten terriers and American Staffordshire terriers. Not surprisingly, the breeds over-represented in the AD group were the same ones observed in the whole study population because this group accounted for 85.38% of the cases. The French bulldog was overrepresented in an ALD cohort investigated previously. The present study did not find any overrepresented breeds in the ALD group, again indicating regional differences.

评估品种AD易感性的研究显示出明显的区域差异，然而拉布拉多寻回犬在不同地点的不同研究中经常被报道，所以我们的结果与之前的研究一致。在我们的研究中，其他被高估的品种是软毛㹴、英国斗牛犬和美国斯塔福德㹴。在澳大利亚进行的一项研究中，英国斗牛犬和美国斯塔福德㹴也显示出患AD的风险增加;在一项全球多中心研究中，斗牛犬(英斗和法斗加起来)的比例过高。此外，瑞士的一项研究报告了软毛㹴和美国斯塔福德㹴的易感。不足为奇的是，在AD组中易感犬种与在整个研究群体中观察到的犬种是相同的，因为这一组占了85.38%的病例。法国斗牛犬在之前调查的ALD队列中被高估了。本研究未发现ALD组中有任何易感的品种，再次表明了区域差异。

 

Human patients with IAD have been reported to have significantly lower SCORAD scores, which measures the severity of skin lesions, compared to EAD. Moreover, in a study, IAD patients used tacrolimus, emollients and antihistamines significantly less frequently and reported a better quality of life than EAD patients, suggesting less severe disease in this subtype.1 In the present study, we used number of body sites affected and pruritus scores at the first visit and maintenance treatment scores as surrogates of disease severity. No significant differences in any of these variables were found between the groups. Likewise, a previous study did not find any significant differences in clinical scores between the ALD and AD groups, but no specific information on the scores used was provided. These results suggest that, in contrast to humans, disease severity is similar in dogs with AD and ALD. However, prospective studies including larger numbers of dogs, especially with ALD, are needed to corroborate this hypothesis.

据报道，与EAD相比，人类IAD患者的SCORAD评分(测量皮损的严重程度)明显较EAD低。此外，在一项研究中，IAD患者使用他克莫司、润湿剂和抗组胺药物的频率明显低于EAD患者，且生活质量较EAD患者高，表明该亚型疾病较轻。在本研究中，我们使用了机体患病部位数量、第一次就诊时的瘙痒评分和维持治疗评分作为疾病严重程度的替代指标。在这些变量中，没有发现组与组之间有显著差异。同样，之前的一项研究也没有发现ALD组和AD组的临床评分有任何显著差异，但没有提供使用的具体评分信息。这些结果表明，与人类相比，患有AD和ALD犬的疾病严重程度是相似的。然而，包括大量的犬，特别是患有ALD的犬在内的前瞻性研究需要证实这一假设。

 

In humans, IAD patients seem to present more frequently with Dennie–Morgan infraorbital folds, orbital darkening, cheilitis and anterior neck folds than EAD patients. Because of the retrospective nature of the study, we were not able to evaluate if certain disease features occur more frequently in one group than the other, nevertheless, this should be evaluated in prospective studies.

在人医中，IAD患者似乎比EAD患者更经常出现丹尼-摩根眶下皱褶、眼眶变暗、唇炎和颈前皱褶。由于研究的回顾性，我们无法评估某一组是否比另一组更频繁地出现某些疾病特征，然而，这应该在前瞻性研究中进行评估。

 

Pruritus scores and body sites affected also were evaluated following treatment as indirect indicators of response to therapy. No significant differences between the groups were noted in mean pruritus scores and number of body sites affected or reduction of pruritus and affected areas during treatment. A previous study did not observe any difference in response to glucocorticoids but noted that significantly more AD dogs had good response to ciclosporin compared to ALD dogs (92% and 50%, respectively).

治疗后瘙痒评分和机体患病部位也作为治疗反应的间接指标进行评估。在治疗过程中，两组患犬的平均瘙痒评分、机体患病部位数量、瘙痒程度和受瘙痒影响的区域的减少均无显著差异。之前的一项研究没有观察到糖皮质激素的反应有任何差异，但指出与ALD的犬相比，对环孢素有良好反应的AD犬明显更多(分别为92%和50%)。

 

Finally, in humans, IAD has been shown to be a dynamic disease where individuals could develop allergen-specific antibody at a latter disease phase. The ALD patients included in the study were not retested, thus we do not know if this phenomenon occurs in dogs and it will be interesting to investigate this further.

最后，在人类中，IAD已被证明是一种动态疾病，个体可在疾病的后期发展出过敏原特异性抗体。本研究中纳入的ALD患犬没有进行再测试，因此我们不知道这种现象是否发生在犬上，这将是一个有趣的进一步研究。

 

This study has some limitations inherent to its retrospective nature, including the inability to assess and compare lesion severity and disease phenotype between the groups due to the lack of standardization in the lesion description portion of the medical records. Moreover, the small number of dogs in the ALD could have impacted the results. Furthermore, it could be contended that ideally all of the dogs in the AD group should have had positive tests to both IDT and AST, and that this may have provided a more precise comparison of the groups. Likewise, it could be contended that comparison of the two groups in which no cases showed a partial response to food trials (as in the AD group), may have given a more precise assessment of AD versus ALD.

本研究具有一定的局限性，其回顾性的性质，包括由于缺乏标准化的病变描述部分的医疗记录，无法评估和比较组间病变的严重程度和疾病表型。此外，ALD中少量的犬可能会影响结果。此外，可以认为，理想情况下，AD组的所有犬都应该对IDT和AST都有阳性测试，这可能提供了更精确的组间比较。同样，可以争辩说，比较两组中没有出现对食品试验有部分反应的病例(如AD组)，可能对AD和ALD给出了更精确的评估。

 

In summary, in the present study, the soft-coated wheaten terrier, American Staffordshire terrier, English bulldog and Labrador retriever were over-represented in the AD group. No significant differences in age of disease onset, sex, presence of respiratory and ocular signs, percentage of time spent indoors, disease severity and response to therapy were observed between AD and ALD subtypes. The lack of differences could suggest that there are no real differences between the proposed subtypes and, that in fact, they are part of the same dynamic disease. However, future prospective studies including a larger cohort of dogs with AD, and especially with ALD, are needed to support our findings. In addition, such studies should evaluate carefully any differences in disease phenotype, barrier integrity and immunological responses between the subtypes which could help tailor therapy more effectively.

综上所述，在本研究中，软毛麦㹴、美国斯塔福德㹴、英国斗牛犬和拉布拉多寻回犬在AD组中的比例过高。AD和ALD亚型在发病年龄、性别、呼吸和眼部症状、在室内的时间百分比、疾病严重程度和治疗反应等方面均无显著差异。缺乏差异可能意味着所提议的亚型之间没有真正的差异，事实上，它们是同一动态疾病的一部分。然而，未来的前瞻性研究，包括更大的一群患有AD的犬，特别是ALD的犬，需要支持我们的发现。此外，此类研究应仔细评估亚型之间在疾病表型、屏障完整性和免疫反应方面的差异，以帮助更有效地制定治疗方案。

 

 

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