Clinical signs and diagnosis of feline atopic syndrome: detailed guidelines for a correct diagnosis
猫特应性综合征的临床症状和诊断:正确诊断的详细指南(中)
Domenico Santoro* , Cherie M. Pucheu-Haston† , Christine Prost‡, Ralf S. Mueller§ and Hilary Jackson
翻译:王帆
Noncutaneous clinical signs associated with FASS
与FASS相关的非皮肤临床症状·
The true frequency in which cats with FASS develop extracutaneous clinical signs is unknown. In most reports with a dermatological bias, no mention is made of noncutaneous signs at all, which may be because they were not present or simply were not recorded for inclusion in the paper. Alternately, concurrent noncutaneous signs may be masked by anti-inflammatory therapy directed towards the skin disease.
患有FASS的猫出现非皮肤临床症状的真实比例尚不清楚。在大多数有皮肤倾向的报告中,根本没有提到非皮肤症状,这可能是因为它们不存在或只是没有被记录在论文中。另外,并发的非皮肤症状可能被针对皮肤疾病的抗炎治疗所掩盖。
Specifics regarding the presence of noncutaneous signs were provided in seven manuscripts. One of these included some cats with concurrent flea (11 of 45) and/or food allergy (six of 45), both of which were presumably in remission when the diagnosis was made. Of the 230 cats described in these seven manuscripts, 8.3% (19 of 230) of the cats reportedly had some form of respiratory disease, of which five had sneezing, three had asthma and 11 had nonspecified respiratory signs.Conjunctivitis was reported in 4.8% (11 of 230) of the cats and nonspecified digestive signs in 3.9% (nine of 230). Overall, there were 39 instances of noncutaneous signs reported; however, several of these cats had more than one condition (e.g. rhinitis and conjunctivitis). Because these manuscripts include only a minority of the reported cases of FASS, it is unclear whether these values may be generalised to the atopic feline population as a whole.
关于存在非皮肤症状的细节在七份手稿中提供。其中包括一些同时患有跳蚤(45只猫中有11只)和/或食物过敏(45只猫中有6只)的猫,这两种猫在诊断时都可能处于缓解状态。在这7份手稿中描述的230只猫中,据报道8.3%(230只猫中的19只)患有某种形式的呼吸系统疾病,其中5只打喷嚏,3只哮喘,11只非特异性呼吸症状。据报道,有4.8%(230只猫中的11只)患有结膜炎,3.9%(230只猫中的9只)有不明确的消化症状。总的来说,有39例报告的非皮肤症状;然而,其中几只猫有不止一种疾病(例如鼻炎和结膜炎)。由于这些手稿只包括了少数报告的FASS病例,尚不清楚这些值是否可以推广到整个特应性疾病猫群体。
Association of FASS with flea and food allergy. In many case series focusing on cats with FASS, cases with concurrent flea or food allergy have been specifically excluded for the purpose of clarity. For this reason, the relatively small number of manuscripts in which this information has been provided limits estimation of the frequency with which other allergic skin diseases appear concurrently with FASS. Together, these manuscripts describe 321 cats with FASS, of which 74 cats had concurrent flea allergy, food allergy or both. If all of the cats are examined as a group, flea allergy was present in association with FASS in 16.5% (53 of 321) of cats reported in these studies. Concurrent food allergy was seen in 5.9% (19 of 321) of the patients and 0.6% (two of 321) of the patients were affected by all three disorders. These figures should be interpreted with some degree of caution, as the focus of these particular manuscripts was on FASS, and some cases with food- or flea-related issues may have been missed, or excluded based upon individual differences in diagnostic criteria. Alternately, cats with flea allergy started on aggressive flea control in the autumn or winter may be mistakenly characterised as having seasonal allergic dermatitis consistent with FASS.
FASS与跳蚤和食物过敏的关系。在许多关注FASS患猫的病例系列中,同时有跳蚤或食物过敏的病例已被明确排除。因此,提供这一信息的相对较少的手稿限制了对其他过敏性皮肤病与FASS同时发病的评估。这些手稿共描述了321只FASS患猫,其中74只猫同时患有跳蚤过敏、食物过敏或两者兼有。如果将所有猫作为一个群体进行检查,在这些研究中报道的16.5%(321只猫中的53只)的跳蚤过敏与FASS有关。5.9%(19 / 321)的患猫同时发生食物过敏,0.6%(2/321)的患猫时发生这三种疾病。对这些数字的解释应该有一定程度的谨慎,因为这些特定手稿的重点是FASS,一些与食物或跳蚤相关的问题可能被遗漏,或基于诊断标准的个体差异被排除。另外,在秋天或冬天开始积极控制跳蚤过敏的猫可能会被错误地定性为与FASS一致的季节性过敏性皮炎。
However, these figures may be somewhat misleading, as there was great variability in the prevalence of concurrent flea allergy and food allergy between manuscripts. Specifically, FASS cats with concurrent flea allergy represented 100%, 48.5%, 33.3%, 24.4% and 0% of the cases reported in their corresponding studies.The reason for this extreme variability is uncertain. However, review of another report from one of these authors covering the same time period suggests that feline flea allergy may simply represent an unusual diagnosis (3.7% of 1,497 cases) at that institution.This particular institution is located in the upper northeastern portion of the United States, suggesting that the low reported prevalence of flea allergy may be more reflective of a relatively low flea population overall (geographical location) rather than a decreased relative frequency of flea allergy.
然而,这些数字可能有些误导,因为手稿中关于并发跳蚤过敏和食物过敏的发病率多变。具体而言,FASS猫同时患有跳蚤过敏的案例在相应研究中分别占100%、48.5%、33.3%、24.4%和0%。这种差异大的原因还不确定。然而,对同一时期一位作者的另一份报告的回顾表明,在该机构,猫跳蚤过敏可能只是一种不常将的诊断(占1497例的3.7%)。这个特殊的机构位于美国的上东北部,这表明跳蚤过敏的低流行率可能更多地反映了跳蚤总数相对较低(地理位置),而不是跳蚤过敏的比例相对下降。
Other possible reasons for the variation in the reported frequency of flea allergy include the more recent availability of more user-friendly and effective flea control products, as well as individual differences in the criteria required to diagnose flea allergy. For example, one investigator might diagnose flea allergy solely based upon the clinical response to insecticidal therapy, while others might require the concurrent presence of positive serology or intradermal test results or response to live flea challenge. Finally, the possibility cannot be excluded that the diagnosis of flea allergy may have been missed in some cases as a consequence of confounding variables such as (unreported) poor owner compliance.
报告的跳蚤过敏比例变化的其他可能原因包括:最近出现了更方便使用和有效的跳蚤控制产品,以及诊断跳蚤过敏所需标准的个体差异。例如,一名研究人员可能仅根据对杀虫剂治疗的临床效果来诊断跳蚤过敏,而其他研究人员可能需要同时存在的阳性血清学或皮内试验结果或对活跳蚤激发的反应。最后,不能排除的可能性是,在某些病例中,由于混杂变量,如(未报告的)宠主依从性差,跳蚤过敏的诊断可能会漏诊。
By contrast with flea allergy, the presence of food allergy was less variable, with 13.3%, 6.1% and 4.6% of cats affected in three studies, and 0% affected in both of the final two studies.
与跳蚤过敏相比,食物过敏的变化较小,在三项研究中,13.3%、6.1%和4.6%的猫患病,最后两项研究均为0%。
Other diseases in the FAS spectrum
其他FAS疾病
Feline food allergy
猫食物过敏
Because of the striking clinical similarities between FASS and food allergy, it is essential to perform a strict food trial to identify and/or rule out a diagnosis of food allergy in cats before starting diagnostics for FASS. As in dogs, a strict food trial (only the prescribed diet and water) should be followed using either a novel limited ingredient (commercial or home cooked diet) or a hydrolysed diet. During the trial, anti-inflammatory medications may be allowed in the initial stages to ameliorate the clinical signs and improve the quality of life for pets and their owners. In some circumstances a second diet trial may be required to confidently rule out food allergy.
由于FASS和食物过敏之间惊人的临床相似性,在开始对FASS进行诊断之前,有必要进行严格的食物试验,以确定和/或排除猫的食物过敏诊断。就像对犬一样,应严格遵循食物试验(只提供规定的日粮和水),使用一种新奇限制成分(商业或家庭自制日粮)或水解日粮。在试验期间,可能会在初始阶段允许抗炎药物,以改善宠物临床症状和宠主生活质量。在某些情况下,可能需要进行第二次食物排查试验,以有把握地排除食物过敏。
A review of the literature (1982–2014) revealed 243 cats diagnosed with food allergy. Concurrent FASS was reported in 2.4% (24 of 243) of cats and FAD in 0.002% (two of 243) of them, with only one cat having both FASS and FAD. However, it should be noted that there will be bias in these figures as the majority of publications were selecting for cats with confirmed food allergy.
一项文献回顾(1982-2014)显示,243只猫被诊断为食物过敏。2.4%(243只猫中有24只)同时患有FASS, 0.002%(243只猫中有两只)同时患有FAD,只有一只猫同时患有FASS和FAD。然而,应该注意的是,这些数据会有偏差,因为大多数出版物选择的是被证实对食物过敏的猫。
In 10 studies, the age of onset of clinical signs was detailed and of these 95 cats, 27% (26 of 95) developed clinical signs before the age of 12 months. The age range of disease onset was three months to 13 years with mean calculations between 3.4 and 4.9 years. A median range of onset was not possible to determine from the published data. Domestic short hair cats were the predominant breed, although purebred cats also were reported in small numbers. In one study, Siamese cats were computed to be at increased risk (RR 5.0) compared with the hospital population. The female:male ratio (where reported) was 1.4:1.
在10项研究中,研究人员详细记录了猫出现临床症状的年龄,在这95只猫中,27%(95只猫中的26只)在12个月前出现临床症状。发病年龄范围为3个月至13岁,平均计算为3.4至4.9岁。从公布的数据无法确定发病的中位值范围。家养的短毛猫是主要的品种,但纯种猫也有少量报道。在一项研究中,与医院病例数相比,暹罗猫的风险增加(RR 5.0)。报道的雌性与雄性的比例为1.4:1。
Reports of clinical signs are varied, making conclusions about “typical” presenting clinical signs difficult. The data from nine studies involving 153 cats with food allergy either reported specific reaction patterns (e.g. MD, HNP, SIAH, EGC), or allowed extrapolation to one or more of these patterns. Head and neck pruritus was reported in 42% (65 of 153), SIAH in 52% (80 of 153), MD in 31% (47 of 153) and EGC in 18% (28 of 153) of the cats. Pruritus was invariably present. Other reported cutaneous signs included urticaria, nonpruritic cutaneous nodules and plasma cell pododermatitis. Involvement of the ears was frequently reported, yet differentiation between the pinna and ear canal was unclear. Extracutaneous signs were reported in five studies; gastrointestinal signs (e.g. flatulence, vomiting and diarrhoea) affected 18% (15 of 83) of the cats, conjunctivitis was present in 12% (nine of 75), respiratory signs in 11% (seven of 61) and hyperactivity in one cat. A favourable response to antipruritic doses of oral or topical (one cat) glucocorticoids was reported in 85% (23 of 27) of cases, whilst no response to injectable glucocorticoids was seen in another study.
临床症状的报道多种多样,很难对“典型”临床症状下结论。涉及153只食物过敏猫的9项研究的数据要么报告了特定的反应模式(例如MD、HNP、SIAH、EGC),要么允许推断这些模式中的一种或多种。42%(153只猫中有65只)报告有头颈部瘙痒,52%(153只猫中有80只)有SIAH, 31%(153只猫中有47只)有MD, 18%(153只猫中有28只)有EGC。瘙痒总是存在的。其他报告的皮肤症状包括荨麻疹、非瘙痒性皮肤结节和浆细胞足皮炎。耳廓患病的病例较多,但耳廓与耳道的区分不清楚。有5项研究报道了皮肤外症状;18%(83只猫中有15只)出现肠胃症状(如胀气、呕吐和腹泻),12%(75只猫中有9只)出现结膜炎,11%(61只猫中有7只)出现呼吸症状,一只猫出现多动症。据报道,85%(23 / 27)的病例对口服或外用(一只猫)糖皮质激素止痒剂有良好的反应,而在另一项研究中,注射糖皮质激素没有反应。
In these studies, the diagnosis of food allergy was achieved by conducting a hypoallergenic diet trial using a limited antigen or novel protein diet selected on the basis of the cat’s previous dietary history. The duration of the diet trial varied from one to 13 weeks, which was generally determined by the time to resolution of clinical signs without the concurrent use of anti-inflammatory medications. In one study, although not ideal, no challenge was performed as the cats’ clinical signs resolved completely and in a second only 59% (10 of 17) of the cats were challenged for the same reason. Because no challenge was performed to confirm the diagnosis of food allergy, the assumption that the nonchallenged cats were indeed food-sensitive must be interpreted with caution. The time to clinical relapse after dietary challenge was reported in three studies and ranged from 15 min to 18 days. In 60 cases the offending allergens were reported and these are tabulated in Table 3.
在这些研究中,食物过敏的诊断是通过低过敏性食物试验实现的,试验使用有限的抗原或根据猫旧日粮史选择的新奇蛋白日粮。食物排查试验的持续时间从1周到13周不等,这通常由临床症状缓解的时间决定,而不同时使用抗炎药物。在一项研究中,虽然不是很理想,但当猫的临床症状完全消失时,没有进行激发,在另一项研究中,同样原因,只有59%(17只猫中的10只)的猫进行了激发试验。由于没有进行激发试验来确认食物过敏的诊断,假设没有激发的猫确实是食物过敏,必须谨慎解释。三项研究中报告了饮食激发后临床复发时间从15分钟到18天。60个病例中报道的过敏原,见表3。
Feline asthma
猫哮喘
Asthma is a common lower airway inflammatory condition in cats with significant morbidity and occasional mortality. From a clinical and pathogenetic point of view, feline asthma is remarkably similar to human asthma, thus justifying the use of the cat as an animal model. As in people, affected cats show a spontaneous and natural hyperexcitability of the airways resulting in reversible bronchoconstriction. Feline asthma is driven by a type-1 hypersensitivity response to aeroallergens, characterised by a T helper 2 cell-dominated cytokine profile [interleukin (IL)-5, IL-4, IL-6 and IL-13].
哮喘是一种常见的下呼吸道炎症疾病,在猫有显著的发病率和偶尔的死亡率。从临床和病理学的角度来看,猫哮喘与人类哮喘非常相似,因此,使用猫作为动物模型是合理的。和人类一样,患猫表现出气道自发和自然的过度兴奋,导致可逆的支气管收缩。猫哮喘是由对空气过敏原的1型超敏反应驱动的,其特征是由T辅助细胞2主导的细胞因子[白细胞介素(IL)-5, IL-4, IL-6和IL-13]。
Affected cats exhibit bronchial hyper-reactivity associated with lower airway inflammation causing dyspnoea with expiratory wheezing, chronic cough and exercise intolerance. The clinical signs observed during an asthma attack result from multiple factors which may include reversible spontaneous bronchoconstriction (airway smooth muscle constriction), oedema of the bronchial mucosa, excessive mucus production and chronic airway remodelling. Generally, cats with asthma are affected by a chronic inflammation of the airways whether or not they have clinical signs. Such inflammation is dominated by eosinophils, which represent the main effector cells of this inflammatory process. They infiltrate the submucosa and the resulting damage may lead to epithelial desquamation. The asthmatic cat may present with an acute onset of expiratory dyspnoea with respiratory distress, open-mouth breathing, hyperpnoea, tachypnoea, pallor, cyanosis and collapse. The clinical signs are usually reversible with combined administration of glucocorticoids, a bronchodilator and oxygen. In some cases, a chronic cough may be the only clinical sign observed. Auscultation reveals wheezes and expiratory cracklings. The thorax may be hyper-resonant due to chronic pulmonary overinflation. Auscultation between episodes of bronchoconstriction may be completely normal. It should be remembered that coughing in the cat may resemble vomiting, because many cats will terminate a paroxysm of coughing with a retch, mimicking hacking up hairballs. Exercise intolerance in younger or more active cats often is noted.
患猫表现出与下呼吸道炎症相关的支气管高度反应性,导致呼吸困难,呼气喘鸣,慢性咳嗽和运动不耐受。哮喘发作期间的临床症状是由多种因素引起的,包括可逆的自发性支气管收缩(气道平滑肌收缩)、支气管黏膜水肿、粘液过多产生和慢性气道重塑。一般来说,患有哮喘的猫会受到呼吸道慢性炎症的影响,无论它们是否有临床症状。这种炎症以嗜酸性粒细胞为主,它代表着这一炎症过程的主要效应细胞。它们浸润粘膜下层,造成的损伤可导致上皮脱落。哮喘猫可能出现急性发作的呼气困难,伴有呼吸窘迫、张口呼吸、呼吸增强、呼吸急促、脸色苍白、发绀和虚脱。临床症状·通常是可逆的联合给药糖皮质激素,支气管扩张剂和氧气。在某些病例中,慢性咳嗽可能是唯一观察到的临床症状。听诊为喘鸣和呼气爆破音。胸腔可能因慢性肺过度膨胀而产生高鼓音。两次支气管收缩之间的听诊可能完全正常。要记住,猫的咳嗽可能类似于呕吐,因为许多猫会以干呕的方式结束一阵咳嗽,模仿起吐毛球。运动不耐受在年轻或更活跃的猫经常被注意到。
Diagnosis of feline asthma
猫哮喘诊断
As for FASS, there is no specific test for routine diagnosis of asthma in cats. Owing to lack of availability of the instrument and technical difficulties, spirometry and total body plethysmography are rarely performed for the diagnosis and monitoring of feline asthma. Diagnosis is based on history, clinical signs, thoracic imaging (Figure 7), bronchoalveolar lavage (BAL) sampling and cytological examination.Ruling out other diseases that mimic clinicopathological features of asthma, including chronic bronchitis, respiratory parasites, heart disease, pneumothorax, fluid effusions, tumours, foreign bodies, bacterial or viral infections, is essential.
至于FASS,目前还没有针对猫哮喘的常规诊断的特异性检测。由于缺乏可用的仪器和技术上的困难,肺活量测定和全身体积描记术很少用于猫哮喘的诊断和监测。诊断依据是病史、临床症状、胸部影像学(图7)、支气管肺泡灌洗(BAL)采样和细胞学检查。必须排除与哮喘临床病理特征相似的其他疾病,包括慢性支气管炎、呼吸道寄生虫、心脏病、气胸、液体积液、肿瘤、异物、细菌或病毒感染。
Thoracic imaging (X-ray or computed tomography)
胸腔影像(X线或CT)
Radiographs commonly demonstrate a bronchial pattern with thickening of the bronchial walls due to the presence of peribronchial infiltrates, in a pattern suggestive of “doughnuts" or "rails". Pulmonary hyperinflation often is seen, causing flattening of the diaphragm. Local atelectasis also is described, most often involving collapse of the right middle lobe. The presence of air in the stomach and digestive tract may be associated with aerophagia that accompanies dyspnoea. However, some asthmatic cats may have normal thoracic radiographs. Computed tomography (CT) can be used for evaluating asthmatic cats as a complement to radiographs. The use of a Plexiglas cylinder allows acquisition of images with light or no sedation. Although CT is useful to differentiate asthmatic cats from healthy cats, it does not discriminate asthma from other lower-airway diseases.
x线片通常表现为支气管模式,由于支气管周围浸润,支气管壁增厚,提示“甜甜圈征”或“轨道征”。常见肺部过度通气引起横膈膜变平。也可见局部肺不张,最常见的是右中叶塌陷。胃和消化道中存在空气可能与伴呼吸困难的吞气症有关。然而,一些哮喘猫可能胸片正常的。计算机断层扫描(CT)可用于评估哮喘猫作为x线检查的补充。有机玻璃圆筒的使用允许在有光或没有镇静的情况下获取图像。尽管CT有助于区分哮喘猫与健康猫,但它不能区分哮喘与其他下呼吸道疾病。
Airway sampling
气道采样
Cytological examination of the BAL is the key for differential diagnosis from chronic bronchitis. Whilst neutrophils are the markers of chronic bronchial inflammation, asthma is characterised by eosinophilic inflammation. In healthy cats eosinphilis comprise in 6–7% (up to 18%) of the total BAL cell population. Bronchial eosinophilia is defined as the eosinophil count exceeding 17–20%. When undertaking glucocorticoid therapy, administration should be stopped for 48 h before performing the respiratory endoscopic examination and fluid collection. Although bacteriological cultures are recommended to rule out infectious diseases in asthmatic cats, they are most often negative. Feline asthma is rarely complicated by a bacterial infection.
BAL细胞学检查是鉴别慢性支气管炎的关键。慢性支气管炎症的标志是中性粒细胞,而哮喘的特征是嗜酸性炎症。在健康的猫中,嗜酸性粒细胞占BAL细胞总数的6-7%(高达18%)。支气管嗜酸粒细胞增多症定义为嗜酸粒细胞计数超过17-20%。在进行糖皮质激素治疗时,应停药48 h,然后进行呼吸内镜检查和液体采样。虽然建议进行细菌培养排除感染性疾病的哮喘猫,但结果通常是阴性。猫哮喘很少并发细菌感染。
Additional diagnostic tests
其他诊断性检查
Other useful diagnostic tests to confirm feline asthma and rule out other differentials may be necessary. These include a complete blood cell count (peripheral eosinophilia is an inconsistent finding in asthmatic cats), faecal examination (faecal flotation and Baermann technique to search for Aelurostrongylus abstrusus and Eucoleus aerophilus) and heartworm testing (to rule out dirofilariosis due to Dirofilaria immitis).
其他有用的诊断测试来确认猫哮喘和排除其他鉴别诊断可能是必要的。这些包括完整的血细胞计数(外周嗜酸性粒细胞增多症在哮喘猫上的发现不一致),粪便检查(粪便浮法和Baermann技术来寻找猫肺线虫和嗜风真线虫)和心丝虫测试(排除由犬心丝虫引起的心丝虫病)。 |