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Higher prevalence of seizure activity in a small population of atopic dogs: a retrospective breed- and age-matched study 一小群特应性皮炎犬中癫痫的发病率更高:一个和品种与年龄匹配的回顾性研究
作者：Ina Herrmann , Clarissa Kradischnig, Ondrej Skor, Akos Pakozdy and Lucia Panakova 翻译：朱锋 Background – Atopic dermatitis (AD) is considered to be a systemic disease in people shown to have an association with epilepsy. However, so far, no data about the association of epilepsy and atopy have been reported in dogs. Objectives – Given the homology between human and canine AD, and the increased incidence of epilepsy in atopic people, we investigated the association between AD and seizure-associated activity in a small canine population. Animals – We included 34 atopic dogs and 34 breed- and age range-matched nonatopic dogs. Methods and materials – We investigated the association between canine AD and signs of seizures in a retrospective, breed- and age range-matched, case-controlled study. Dog owners were interviewed using a standardized questionnaire. The presence or absence of signs of seizure activity and possible comorbidities were questioned. Results – Seven of the 34 atopic dogs also suffered from seizure activity. By contrast, only one dog affected with seizure signs could be identified among the 34 nonatopic dogs. Atopic dermatitis was associated with a higher frequency of seizure activity (McNemar test, P = 0.035; one-sided) and atopic dogs had a higher odds ratio to develop seizures [(95% CI) 7 (0.9–56.9)] compared to the age- and breed-matched nonatopic control group. No other comorbidities were detected. Conclusion and clinical importance – In our small retrospective study, we observed an increased prevalence of seizure activity in the atopic dog population. Further larger and prospective studies are needed to confirm these results. 背景-特应性皮炎(AD)被认为是人类的一种与癫痫相关的全身性疾病。然而，到目前为止，还没有关于犬癫痫和特应性皮炎之间关系的数据报道。 目的-考虑到人AD和犬AD的同源性，以及特应性皮炎患者中癫痫发病率的增加，我们在少数犬中调查了AD和癫痫发作的相关性。 动物-包括34只患特应性皮炎的犬和34只品种和年龄范围匹配的无特应性皮炎的犬。 方法和材料-我们通过回顾性、品种和年龄范围匹配的病例对照研究，调查了犬AD和癫痫发作之间的关系。研究人员使用标准化问卷对宠主进行了采访。询问是否有癫痫发作症状和可能的合并症。 结果-34只特应性皮炎犬中有7只也出现癫痫发作。相比之下，在34只无特应性皮炎的犬中，只有一只有癫痫症状。特应性皮炎与较高的癫痫发作频率有关(McNemar检验，P = 0.035），与年龄和品种匹配的非特应性皮炎对照组相比，有特应性皮炎的犬发生癫痫的比例更高[(95%置信区间) 7(0.9-56.9)]。未发现其他合并症。 结论和临床重要性-在我们的小型回顾性研究中，我们观察到在特应性皮炎患犬中癫痫发作的发病率增加。需要进一步更大规模和前瞻性的研究来证实这些结果。
Introduction 介绍 Atopic dermatitis (AD) is a chronic, pruritic and inflammatory skin disease in dogs that reveals many similarities to human AD. The pathogenesis of AD in humans and dogs is multifactorial involving genetics, environmental exposure and immunoglobulin (Ig)E-sensitization against environmental and food allergens. A key feature of AD is the inflammatory component, shown to be a systemic response affecting many organ systems, not only the skin. In people, numerous studies have reported AD-associated comorbidities including asthma, hay fever, extracutaneous and cutaneous infection, psychological and behavioural comorbidities, and epilepsy. Two studies in humans, conducted in Taiwan and the United States, have shown the association between having AD and an increased risk of developing epilepsy later in life. In the US, an odds ratio (OR) of 1.72 was calculated for atopic children to develop epilepsy later in life. Interestingly, having severe AD signs increased the OR to 23.89. In Taiwan, an increased incidence of epilepsy was reported in 35312 atopic people in comparison to age- and sex-matched controls. Except for an increased risk of atopic dogs developing epitheliotropic T-cell lymphoma, data about AD-associated comorbidities in dogs are widely lacking. We hypothesized that, analogous to people, atopic dogs have an increased risk of developing seizures and epilepsy. Therefore, this retrospective study aimed to investigate the association between seizure activity and canine AD when compared to a breed- and age range-matched, nonatopic control group, 特应性皮炎(AD)是一种慢性、瘙痒性和炎性犬皮肤病，与人AD有许多相似之处。人和犬的AD发病机制是多因素的，涉及遗传、环境暴露和免疫球蛋白(Ig) E对环境和食物过敏原的敏感。AD的一个关键特征是炎症成分，这是一种影响许多器官系统的全身反应，而不仅仅是皮肤。在人类中，许多研究报告了AD相关的合并症，包括哮喘、花粉热、皮肤外和皮肤感染、心理和行为合并症以及癫痫。在中国台湾和美国进行的两项人类研究表明，患有AD与生命后期发生癫痫的风险增加相关。在美国，计算出特应性疾病儿童在以后的生活中发生癫痫的比例(OR)为1.72，有趣的是，有严重AD症状会使OR升高到23.89。在台湾，与年龄和性别匹配的对照组相比，有35312例特应性疾病患者的癫痫发病率增加。除了特应性皮炎犬发生趋上皮性T细胞淋巴瘤的风险增加外，关于犬AD相关合并症的数据普遍缺乏。我们假设，与人相似，特应性皮炎犬患抽搐和癫痫的风险更高。因此，本回顾性研究旨在研究与品种和年龄范围匹配的非特应性皮炎对照组相比，癫痫发作与犬AD之间的相关性。
Methods and materials 方法和材料 Study design 研究设计 We investigated the association between canine AD and seizure activity in a retrospective, breed- and age range-matched, case-control study, following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Dogs with AD were selected and an owner questionnaire was completed over the telephone. The seizure-associated signs were collected and reported based on the owner-reported signs. Following the inclusion of 100 AD patients, breed- and age range-matched dogs were searched, and owners were asked to complete the same questionnaire as given previously to the owners of the atopic dogs. Verbal or written consent was given by all owners before participating in this study. The OR was calculated between dogs having seizures in the AD group and the control group, defining the primary outcome measurement. Likewise, we included other concurrent diseases in the questionnaire to find additional AD-associated comorbidities. 我们在遵循加强流行病学观察研究报告(STROBE)指南的前提下，在一项与品种和年龄范围相匹配的回顾性病例对照研究中，我们研究了犬AD与癫痫发作的关系。我们选择AD患犬，然后通过电话填写问卷调查表，根据宠主提供的症状报告我们收集有癫痫发作相关症状的患犬。通过电话填写主人问卷。收集癫痫发作相关症状并根据业主报告的症状报告。在纳入100名AD患犬后，研究人员对与品种和年龄范围匹配的其他犬进行了搜索，并要求宠主填写与之前给特应性皮炎患犬的宠主相同的问卷。所有宠主在参与本研究前均给予口头或书面同意。计算有癫痫发作的AD组和对照组之间的OR值，确定主要结果测量值。同样，我们在问卷中纳入了其他并发疾病，以发现其他AD相关的合并症。
Questionnaire 问卷调查 An identical questionnaire was given to all participating owners and consisted of 10 questions. The English version (original in German language) is shown in Appendix S1. The form includes questions about any general diseases of the dog and any medication given long-term or periodically. Detailed questions about any clinical signs that can be associated with AD and/or repeated seizures are included. Only completed questionnaires were accepted; partially completed forms led to exclusion of the dog. 所有参与调查的宠主都收到了一份相同的问卷，其中包括10个问题。英文版本(原文为德语)见附录S1。这张表格包括关于犬的全身性疾病和任何长期或定期服用药物的问题。对可能与AD和/或反复发作相关的任何临床症状的详细问题也包括在内，只接受问卷填写完整的动物，排除了未全部完成问卷的。
Matching 匹配 In this study, cases were matched to controls 1:1. The exact breed was matched and any mixed-breed dogs were excluded. Atopic dogs were matched to nonatopic dogs with an age range of 2 years in <8-year-old dogs and 4 years in >8-year-old dogs. This allowed us to increase patient numbers. No sex matching was applied. 在本研究中，病例组与对照组1:1匹配。准确的品种是匹配的，任何混血犬都被排除在外。特应性皮炎患犬与非特应性皮炎犬相匹配，小于<8岁犬的年龄范围在2年内，>8岁犬的年龄范围为4年内。这使得我们能够增加病人数量。性别问题未做考虑。
Animals 动物 Atopic dermatitis group Client-owned dogs diagnosed with AD between 2010 and 2017 by the University of Veterinary Medicine Vienna were searched through the hospital electronic database. Canine AD was diagnosed based on clinical signs, exclusion of other pruritic diseases and an eight-week strict food trial with a commercial or homemade elimination diet. Dogs with AD resulting from environmental triggers were included; however, coexisting food allergy was allowed. A list of all qualifying atopic dogs seen in the aforementioned timeline was generated. The person contacting the owners was not involved in any patient care and did not see the full medical record of the dogs. All owners were first asked via email about their willingness to participate in a health-related study without mention of AD or seizure activity before participation agreement. When consent was given, they were called later to participate in the study. Each of the 10 questions was read to the owners and additional questions from the owners were discussed. The verbal answer was documented in a written form on the questionnaire. All telephone calls and communications with the owners were performed by one author between October 2016 and July2017. Initially, 100 dogs with AD were questioned to generate a sufficiently large study population. 通过医院电子数据库检索维也纳兽医大学在2010年至2017年期间被诊断为AD的犬。犬AD的诊断是基于临床症状，排除其他瘙痒性疾病，并通过商品化或自制的饮食进行8周严格的食物排除试验。研究对象包括环境诱发的AD犬。然而，允许同时存在食物过敏。生成了上述时间线中所有符合条件的特应性皮炎犬的列表。联系宠主的人没有参与任何动物的护理，也没有看到患犬的完整医疗记录。通过电子邮件，向所有宠主首先询问他们是否愿意参加一项与健康有关的研究，在参与协议之前不提及AD或癫痫发作。获得同意后，随后受邀参与研究。向宠主阅读全部的十个问题，并讨论了宠主提出的其他问题。口头回答并以书面形式记录在问卷上。所有与宠主的电话和沟通都是由一名作者在2016年10月至2017年7月期间进行的。最初，100只患有AD的犬被询问以产生足够大的研究群体。
Control group 对照组 The control group was recruited during a dog training camp, a dog show event and via dog training facilities. Dog owners were asked about the breed and the age of their dog with no further information requested before inclusion in the study. The owners of identified controls were given the questionnaire and assistance was given in case of any questions. To increase the population,matched controls also were searched in the hospital electronic database and contacted in the same manner as the owners of the dogs with AD. The recruitment of control dogs happened between November 2016 and July 2017 following the same author questioning the owners of dogs with AD. In case of a provided answer being suggestive of allergic disease, the case was excluded from the study and a new match was searched. Compatible breed and age were the only inclusion criteria for the control cases; no healthy status was evaluated or asked for before the inclusion of the dog. 对照组是在犬训练营、犬展活动和犬训练机构中招募的。向宠主询问犬的品种和年龄，在纳入研究之前没有要求进一步的信息。向符合对照组要求的宠主发放调查表，并在有任何问题时给予协助。为了增加实验动物数量，还在医院的电子数据库中搜索了匹配的对照，并用和患AD犬的宠主相同的方式联系。研究人员在2016年11月至2017年7月期间招募了对照组犬，此前该作者还询问了患有AD犬的宠主。如果提供的答案提示过敏性疾病，则将该病例排除在研究之外，并继续搜索匹配的动物。对照组的唯一入组标准为匹配的品种和年龄;入组前未评估或询问犬的健康状况。
Statistical analyses 统计分析 In order to test our hypothesis that atopic dogs have an increased risk of developing seizure activity and epilepsy in a breed- and age matched case-control study, we used McNemar’s test. McNemar’s test was calculated to evaluate an association between atopy and seizures, reporting one-sided P-value (P < 0.05) and OR with 95% confidence interval ( http://vassarstats.net/propcorr.html; page last accessed July 12, 2020). 为了验证我们的假设，即在一项与品种和年龄匹配的病例对照研究中，患有特应性皮炎的犬发生癫痫发作 和癫痫的风险更高，我们使用了McNemar的测试。计算McNemar’s检验评估特应性疾病 与癫痫发作之间的关系，报告单侧P值(P < 0.05)和OR, 95%置信区间（http://vassarstats.net/propcorr.html;页面最后访问时间为2020年7月12日)。
Results 结果 We included 68 dogs, grouped into 34 breed- and age matched pairs. Detailed patient data are shown in Appendix S2. The mean age differed minimally between the AD group (6.3 years) and the control group (6.8 years)as a consequence of the age range-matching and not exact age-matching. The most commonly represented breeds included German shepherd dog (10 dogs), Labrador retriever (eight dogs) and ShibaInu (six dogs). The overall female:male ratio was 2:1 (45 female, 23 male).Among female spayed dogs, 14 individuals were in the AD group and 19 in the control group. The ratio for female intact was 8 (AD) to 4 (control), for male 5:7 and male intact 7:4. Overall, 13 pairs were sex- and neuter status matched, six pairs were sex-matched and not neuter status-matched, and 15 pairs were of mixed sex. In the AD group, seven of 34 (21%) dogs were reported to have seizures compared to only one of 34 (3%) individuals in the control group. McNemar’s test showed a statistically significant association between canine AD and signs of seizures (P < 0.035, one-sided) (Table 1). Atopic dogs had as even-fold greater likelihood of developing seizure activity compared to nonatopic dogs [OR (95% CI) 7 (0.9–56.9)]. Detailed information about the dogs with seizure activity is shown in Table 2. The mean age of the atopic dogs with signs of seizures was 8.9 years at the time of questioning. Information about the age of the dogs at the onset of seizures was not requested. According to the owners, six dogs had generalized epileptic seizures and two dogs had focal epileptic seizures. All eight owners reported that the diagnosis was made by a primary care veterinarian and seven dogs were taking anti-epileptic medication. All other comorbidities were reported only once in the study population. No statistics were calculated to evaluate a correlation between seizures and anti-inflammatory medication or canine AD and other comorbidities owing to the low number of seizure cases and reported comorbidities.Anti-allergic medications administered to the atopic dogs are shown in Appendix S3. 我们纳入68只犬，分成34对品种和年龄匹配的犬。详细的病患资料见附录S2。AD组(6.3岁)和对照组(6.8岁)的平均年龄差异很小，这是年龄范围匹配而不是确切的年龄匹配的结果。最常见的品种包括德国牧羊犬(10只)、拉布拉多寻回犬(8只)和柴犬(6只)。公母比例为2:1(45只母犬，23只公犬)。在母绝育犬中，AD组有14只，对照组有19只。未绝育母犬中AD组8只，对照组4只。绝育公犬中AD组5只，对照组7只；未绝育公犬中AD组7只，对照组4只。总的来说，13对已绝育的性别配对，6对未绝育的性别配对，15对是混合的。在AD组，34只犬中有7只(21%)有癫痫发作，而对照组中只有1只(3%)有癫痫发作。McNemar的测试显示，犬AD与癫痫发作症状之间存在统计学意义上的显著关联(P < 0.035，单侧)(表1)。与非AD犬相比，AD犬发生癫痫的可能性要高出一倍[OR (95% CI) 7(0.9-56.9)]。有关癫痫发作犬的详细信息见表2。有癫痫发作症状的特应性皮炎犬的平均年龄为8.9岁。没有要求提供犬在癫痫发作时的年龄信息。据宠主说，有六只犬出现了全身性癫痫发作，两只犬出现了局灶性癫痫发作。所有8名宠主都报告说，诊断是由一位初级护理兽医做出的，7只犬正在服用抗癫痫药物。所有其他合并症在研究群体中仅报道过一次。由于癫痫病例和报告的合并症病例较少，因此没有统计数据来评估癫痫发作与抗炎药物或犬类AD及其他合并症之间的相关性。给过敏性犬服用的抗过敏药物见附录S3。
| 品种 | 年龄 | 有无AD | 曾用药物 | 诊断 | 临床症状 | 抗癫痫药 | 并发症；其他药物 | | | | | | | | | | | | | | | | | | | | | | | | | 抓蝇综合征，强直痉挛性癫痫伴踏板无意识行为，流涎和意识丧失 | | | | | | | | | | | | | | | | | | 伴有踏板无意识行为的强直痉挛性发作， 流涎和失去意识 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Discussion 讨论 Our breed- and age-matched case-control study demonstrated a significant association between seizure activity and atopic status. The incidence of seizures in the healthy control population was 3% compared to 21% in our atopic dogs. Our study reports a seven-fold greater risk of atopic dogs having seizure-associated activity, in agreement with two human studies in which atopic individuals had ORs of 1.79 and 2.32 to develop seizures and epilepsy later in life. 我们的品种和年龄匹配的病例对照研究表明癫痫发作和特应性疾病之间有显著的联系。健康对照组的癫痫发作发生率为3%，而我们的特应性皮炎犬为21%。我们的研究报告显示，患AD犬的出现癫痫的风险增加了7倍，这与两项人类研究一致，在这两项研究中，患特应性疾病的个体在以后的生活中发生癫痫的ORs分别为1.79和2.32。
The mechanisms connecting AD with seizures are unknown, as is the full pathophysiology of either of the diseases. Presumed mechanisms explaining a causality between the development of seizures in atopic individuals involve systemic inflammation, cytokines and mastcells. Following a flare, systemic inflammation occurs in atopic individuals which could affect the blood–brain barrier and the cytokine milieu. For example, elevated levels of interleukin (IL)-17 and IL-1ß have been shown in epileptic people and correlated with seizure frequencies. Likewise, over expression of IL-6 in the brain of transgenic mice led to a predisposition for seizures. By contrast with these potential seizure-triggering T helper cell (Th) 1 and pro-inflammatory cytokines, the early detected cytokines in canine AD are Th2 type cytokines.21 However, less is known about atopic endotypes in dogs and some breeds may indeed have a predominantly Th17-driven inflammation producing IL-17. With time, affected atopic people and dogs switch to a chronic, predominant Th1 response and a pro-inflammatory state, especially with frequent concurrent bacterial infections. Systemic inflammation was shown to induce temporal lobe epilepsy and lead to an impaired blood–brain barrier contributing to the changed cytokine milieu in the brain. AD与癫痫发作的联系机制尚不清楚，这两种疾病的完整病理生理学也是如此。解释特应性皮炎个体和癫痫发作之间因果关系的假定机制涉及全身炎症、细胞因子和肥大细胞。在过敏症发作时，特应性皮炎个体会发生系统性炎症，可能会影响血脑屏障和细胞因子环境。例如，癫痫患者的IL-17和IL-1ß水平升高，并与癫痫发作频率相关。同样，转基因小鼠的大脑中IL-6的过度表达导致了癫痫的易感性。与这些潜在的癫痫触发T辅助细胞(Th) 1和促炎细胞因子相比，犬AD早期检测到的细胞因子是Th2型细胞因子。然而，关于犬的特应性内型知之甚少，一些品种可能确实有主要由Th17驱动的炎症产生IL-17。随着时间的推移，患病人和犬转变为慢性的，主要的Th1反应和促炎状态，特别是在频繁并发细菌感染的情况下。全身性炎症被证明会诱发颞叶癫痫，导致血脑屏障受损，从而导致大脑中细胞因子环境的改变。
Consequently, cells producing cytokines also are assumed to be connected with both diseases. Mast cells, as IgE-dependent and -independent cytokine producers, are found in the brain and in the skin where they contribute to the inflammation. In addition, microglia/macrophages, potent cytokine producers, may play a role in the development of epilepsy and AD. The upregulated inflammatory cells and systemic cytokines produced in atopic individuals could induce neuroinflammation potentially leading to a hyper excitable state inducing seizures. Interestingly, it was also shown that autoimmune diseases, such as systemic lupus erythematosus and type 1 diabetes, are associated with the development of epilepsy, strengthening a plausible inflammatory connection. Thus, it seems that chronic allergic disease might provoke seizures or there could be a common pathway that triggers both diseases. 因此，产生细胞因子的细胞也被认为与这两种疾病有关。肥大细胞，作为IgE依赖性和非依赖性的细胞因子产生者，在大脑和皮肤中发现，它们在那里导致炎症。此外，小胶质细胞/巨噬细胞，强大的细胞因子产生者，可能在癫痫和AD的发展中发挥作用。特应性皮炎个体产生的炎症细胞和全身性细胞因子上调可诱发神经炎症，可能导致高兴奋状态诱发癫痫发作。有趣的是，研究还表明，自身免疫疾病，如系统性红斑狼疮和1型糖尿病，与癫痫的发展有关，加强了可能的炎症联系。因此，似乎慢性过敏性疾病可能引起癫痫发作，或者可能有一个共同的途径触发这两种疾病。
Inflammation may not be the only explanation and could be only part of a multifactorial disease pathogenesis leading to each disease. Therefore, the proof of causality between seizures and AD is complex, and it is reasonable to start with a more detailed understanding of each of these individual diseases. 炎症可能不是唯一的解释，可能只是导致每种多因子疾病的发病机制的一部分。因此，癫痫发作和AD之间因果关系的证明是复杂的，从更详细地了解每一种疾病开始是合理的。
The retrospective nature and the limited patient number are clear limitations of this study. Owing to the matching process, a limited number of dogs with AD could be adequately matched with controls and, therefore, the study remains under powered. Thus, an age range was implemented instead of an exact age match. However, the two-year range should have had minimal effect and the mean age was almost identical in both groups. Owing to the low patient numbers, the effect of anti-allergic medication on seizure activity and the finding of additional comorbidities associated with AD could not be evaluated. 本研究的回顾性和患犬数量有限是其明显的局限性。由于匹配过程，有限数量的AD犬可以与对照组进行充分匹配，因此，这项研究强度不够。因此，实现了一个年龄范围匹配，而不是一个确切的年龄匹配。然而，两年的范围应该对此项研究的影响很小，两组的平均年龄几乎相同。由于患者数量较少，抗过敏药物对癫痫发作的影响以及与AD相关的其他合并症的发现无法评估。
Furthermore, we could only cover signs of seizures reported by the owner; no information was provided by the owner regarding the diagnostic approach or the ultimate type of epilepsy that was diagnosed. However, although all eight owners reported that the diagnosis of epilepsy was made by a primary care veterinarian, no information was available about diagnostic tests to rule out structural forms of epilepsy. Questions regarding the age of seizure onset and the allergy onset were not asked as a result of the concern of inaccuracy in the data. Epilepsy and AD are both chronic diseases, potentially present for years before questioning the owner and the medical records were unavailable to confirm the data. Therefore, this study was not able to provide data on a timeline of disease onset or causality of AD increasing the seizure risk later in the dog’s life. However, this information would be very interesting; these data should be collected in a prospective and ideally longitudinal study, also including cofounding factors such as the severity of AD and medication scores of anti-allergic medications. One longitudinal study in people included patients newly diagnosed with AD and no history of epilepsy and found that the first signs of seizures were reported on average3.3 years after the diagnosis of AD. In addition, the onset of epilepsy in patients with AD was six years younger compared to the age- and sex-matched control group. As a consequence of the design of our cross-sectional study, we cannot exclude the possibility that some dogs in the control group might still develop AD or that some dogs from both groups may develop seizures later in their life. However, 71% of all dogs included in the study were ≥5 years old and 88% were ≥3 years old, and therefore the likelihood of developing AD later in life for this age group is low. In a similar way to AD, the age of onset of idiopathic epilepsy with a genetic or genetically suspected origin for most breeds is usually between six months and 6 years. Next, the question of a seizure preventative effect using strict anti-inflammatory treatment of AD arises. Although no data are available in people that answered this interesting question, future data in dogs could be collected in a proactive study. Another limitation to note is that the control cases were not examined by a veterinarian and potential signs of AD were evaluated based on the questionnaire only. 此外，我们只能通过宠主报告的癫痫症状;宠主未提供关于诊断出癫痫的方法或类型的信息。然而，尽管所有8名宠主报告说，癫痫的诊断是由一名初级保健兽医作出的，但没有关于诊断测试以排除结构性癫痫的信息。由于担心数据不准确，没有询问癫痫发作和过敏发作的年龄。癫痫和AD都是慢性疾病，在询问宠主之前可能存在多年，也没有医疗记录来证实数据。因此，这项研究无法提供有关疾病发作时间轴的数据，或AD增加犬日后癫痫发作风险的因果关系。然而，这些信息会非常有趣;这些数据应该在一个前瞻性和理想的纵向研究中收集，也包括共同的因素，如AD的严重程度和抗过敏药物的药物评分。一项对人群的纵向研究包括了新诊断为AD且没有癫痫史的患者，发现癫痫发作的第一个症状平均出现在确诊AD后3.3年。此外，与对照组相比，AD患者癫痫发作的年龄要小6岁。由于我们的横断面研究的设计，我们不能排除对照组的一些犬仍然可能患AD或两组的一些犬在以后的生活中可能患癫痫的可能性。然而，研究中71%的犬≥5岁，88%≥3岁，因此这个年龄段的犬在以后的生活中患AD的可能性很低。与AD类似，大多数品种的特发性癫痫的发病年龄通常在6个月至6岁之间，病因可能是遗传性的或遗传起源的。接下来，使用严格的抗炎治疗来预防AD发作的问题出现了。虽然目前还没有关于人类的数据来回答这个有趣的问题，但未来在犬上的数据可以通过一项前瞻性研究来收集。另一个需要注意的局限性是，对照组没有经过兽医检查，潜在的AD症状仅基于问卷调查进行评估。
Moreover, female dogs are over-represented (45 total including 33 spayed) in this study. This could relate to the increased risk of female spayed dogs developing AD. By contrast, male dogs, independent of the neuter status, develop epilepsy more frequently than females. However, the female: male ratio was similar between the two groups (22 versus 23 females and 12 versus 11males in the AD and control groups, respectively), and thus the higher epilepsy risk for males does not affect our study results. 此外，在本研究中，母犬的比例过高(共45只，其中33只已绝育)。这可能与绝育母犬患AD的风险增加有关。与此相反，未绝育的公犬比母犬更容易患癫痫。然而，两组的雌性:雄性比例相似(AD组和对照组分别为22：23,12：11)，因此公犬癫痫风险较高并不影响我们的研究结果。
Potential selection bias arose from the recruitment of control dogs at a show and dog training camp. These owners might not report or not be aware of the clinical signs of their dogs compared to the atopic dog owners that sought veterinary specialized care at least once. 潜在的选择偏差来自于在犬展和犬训练营招募的对照组犬。这些宠主可能不报告或不知道他们的犬的临床症状，而患AD犬的宠主至少寻求1次兽医专业治疗。
This is a small retrospective breed-age controlled study that revealed an association between clinical signs of seizures and atopy in concordance with human studies. Despite the study limitations, we were surprised by the high prevalence of seizure activity in dogs with AD and the association in our study population. These results require confirmation, ideally in a prospective, longitudinal study including dogs examined and diagnosed by veterinary neurologists and dermatologists. Based on these results, a detailed history and thorough dermatological and neurological examination of dogs presenting with either condition are recommended. In addition, caregivers may provide better client education and recommend anti-inflammatory disease treatment to patients with AD to prevent systemic inflammation. Finally, further questions to address are the relationships between the time of onset of the diseases and whether the treatment of one disease may influence the other disease in dogs with AD and idiopathic epilepsy. 这是一项小型限定品种和年龄的回顾性对照研究，揭示了癫痫发作的临床症状和特应性皮炎之间的联系与人类研究一致。尽管研究有局限性，但我们对AD犬癫痫发作的高患病率及其在我们研究的群体中的相关性感到惊讶。这些结果需要确认，理想情况下是在前瞻性的、纵向的研究中，包括由兽医神经学家和皮肤科医生检查和诊断的犬。基于这些结果，建议对出现这两种情况的犬进行详细的病史和全面的皮肤和神经学检查。此外，医护人员可以为AD患者提供更好的客户教育，并推荐抗炎治疗，以预防全身性炎症。最后，需要进一步解决的问题是，在患有AD和特发性癫痫的犬中，疾病的发病时间与一种疾病的治疗是否会影响另一种疾病之间的关系。
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发表于 2022-6-8 09:04:00
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