本帖最后由 王帆 于 2021-10-29 21:10 编辑
Malassezia otitis unresponsive to primary care: outcome in 59 dogs 初级常规治疗无效的马拉色菌性耳炎：59例犬疗效总结 作者：Johann M. Boone , Ross Bond , Anette Loeffler , Ewan A. Ferguson and Anke Hendricks
翻译：王帆 Background – Otitis externa (OE) is a common disorder in dogs. Infection by the commensal yeast, Malassezia pachydermatis, may result in chronic disease that does not respond to standard primary care. Chronic infectious OE may be associated with otitis media (OM). Hypothesis/Objective – To report medical management, clinical outcomes and frequency of middle ear involvement, in dogs with Malassezia otitis unresponsive to primary care. Animals – Fifty-nine dogs from one referral veterinary hospital from January 2007 to September 2018. Methods and materials – Retrospective analysis of medical records of dogs referred with chronic otitis and treated for Malassezia otitis at a referral veterinary hospital. Results – Chronic Malassezia OE was treated successfully in 91% of ears, in 87% of these cases with one ear flush intervention. Median time-to-resolution was 27 days after ear flush intervention. Neither duration of otitis, presence of neutrophils in aural discharge nor administration of oral itraconazole affected clinical outcome. Malassezia OM occurred concurrently in 17% of ears. Conclusions and clinical relevance – These findings assist clinicians and carers of affected dogs in decisionmaking, by documenting that most cases of canine Malassezia otitis that have not resolved with standard primary care, can be treated successfully with a well-staged and intense medical treatment plan. Malassezia OM should be suspected to occur concurrently in around a fifth of affected ears.
摘要 背景 – 外耳炎(OE)是犬的常见疾病。被共生酵母菌——厚皮马拉色菌感染, 对初级常规治疗无效, 可能导致慢性疾病。慢性感染性OE可能导致中耳炎(OM)。 假设/目的 – 报告对初级常规治疗无效的马拉色菌耳炎患犬的医疗管理、临床效果和中耳炎发病率。 动物 – 2007年1月至2018年9月, 一家转诊兽医医院的59只犬。 方法和材料 – 转诊的治疗过马拉色菌耳炎的慢性耳炎患犬, 回顾性分析其在转诊兽医医院接受治疗的病历。 结果 – 成功治疗了慢性马拉色菌OE中91%的耳朵, 其中87%的病例进行了单耳冲洗干预。中位消退时间为27天。耳炎期间耳分泌物中存在中性粒细胞或口服伊曲康唑均不影响临床效果。17%的耳朵同时发生马拉色菌OM。 结论和临床相关性 – 初级常规治疗无效的犬马拉色菌耳炎病例, 经过合理分期和有力的药物治疗计划,大部分得以成功治疗, 这些记录发现有助于临床医生和护理者对病犬做更好的决策。应怀疑约五分之一的患耳并发马拉色菌OM。
Introduction 介绍 Otitis externa (OE) is a common diagnosis in dogs and accounts for ≤10% of all canine disorders recorded by primary-care veterinary practitioners in the UK. It is a disorder with significant impact on health-related welfare in dogs. Otitis externa develops as a result of predisposing, primary, secondary and perpetuating factors. Although allergic skin disease is a common primary cause of OE in dogs, secondary infection (bacterial or fungal) is usually the reason dogs are presented for veterinary attention. 外耳炎(OE)是一种犬常见疾病，在英国初级保健兽医从业者记录的所有犬类疾病中占≤10%。这是一种对犬的健康福利有重大影响的疾病。外耳炎是由易感因素、原发因素、继发因素和持久因素引起的。虽然过敏性皮肤病是犬OE常见原发病因，继发感染(细菌或真菌)通常是犬的就诊原因。
Malassezia pachydermatis has long been recognised as a commensal yeast in the ear of dogs and may be associated with OE. In primary-care practice, most cases of Malassezia OE (MalOE) are thought to respond to therapy with combination products authorised for the topical treatment of infectious OE. However, the authors regularly encounter cases of chronic (persistent or recurrent) otitis in their canine referral caseload, with Malassezia as the only identifiable pathogen, based on cytological results from aural discharge alone or in combination with negative aerobic or anaerobic bacterial culture. As the sole pathogen, Malassezia has been identified in 8% and 26% of OE cases. 厚皮马拉色菌长期以来被认为是犬耳道中的一种共生酵母菌，可能与OE有关。在临床初级常规治疗中，认为大多数马拉色菌OE(MalOE)病例对批准用于感染性OE的复方外部治疗产品的治疗有效。然而，作者经常在他们的犬转诊病例中遇到慢性(持久性或复发性)耳炎病例，根据仅有的耳分泌物细胞学检查结果或结合有氧或厌氧细菌培养的阴性结果，观察到马拉色菌是唯一的病原微生物。马拉色菌是唯一的病原微生物，分别在8%和26%的OE病例中被确认。
In such cases, there is a need not only to address the infectious cause, but also to identify and manage predisposing, primary and perpetuating factors such as stenosis of the ear canal, accumulation of debris and middle ear disease. Otitis media (OM) is most commonly thought to occur in dogs when infection extends into the middle ear from the ear canal via a defect in the tympanic membrane, and has been reported to occur in as many as 80% of cases with chronic bacterial OE. Whilst Malassezia is not as well-recognised a cause of OM, several studies have isolated yeast microbes from the middle ear of dogs with OM. Malassezia was reported to be the sole pathogen in five of 22 dogs with OM. 在这些病例中，不仅需要解决感染性病因，还需要确定和管理易感因素、原发因素和持久因素，像是耳道狭窄、耳垢堆积和中耳炎。犬中耳炎(OM)最常见于感染从耳道通过破损的鼓膜蔓延到中耳时，据报道，高达80%的慢性细菌性OE病例发生中耳炎。虽然马拉色菌不是引起OM的一个公认的病因，但一些研究已经从OM患犬的中耳中分离出酵母菌。22例OM患犬中，有5例报道了马拉色菌是唯一的病原微生物。
The aim of this retrospective case series was to broaden recognition of the role of Malassezia in chronic otitis in dogs, to assist primary care clinicians and carers of affected dogs with management decisions by summarising treatment and clinical outcomes in MalOE cases treated at a referral veterinary hospital, and to report the frequency of concurrent Malassezia OM. 本回顾性病例分析的目的是强调马拉色菌在犬慢性耳炎中的作用，通过总结在转诊兽医医院治疗的MalOE病例的治疗和临床效果，帮助初级护理临床医生和患犬的护理人员做出管理决策。同时报告并发马拉色菌OM的发病率。
Methods and materials 方法和材料 Study population 研究对象 Dogs with chronic ear disease were identified by searching the practice management system of a large veterinary referral and teaching hospital (Queen Mother Hospital for Animals, UK) for dogs referred to the dermatology service, having had an otoscopic examination and ear flush procedure under general anaesthesia, and a computed tomography (CT) scan, between 1 January 2007 and 10 September 2018. A parallel search of the hospital’s patient record system for the terms “otitis” and “Malassezia” over the same period was conducted using the Veterinary Animal Surveillance System interface.For all dogs identified in both searches, records then were searched individually to select patients meeting the following inclusion criteria: (i) duration of ear disease episode of at least two months; (ii) having undergone at least one (video)otoscopy-guided ear examination, irrigation and sampling procedure under anaesthesia (designated ear flush intervention, EFI; the day of the first recorded ear flush was then designated EFI1); (iii) having had a CT scan of the ears within four weeks of EFI1; (iv) having had at least one re-examination within six weeks of EFI1; and (v) having a recorded diagnosis of otitis with Malassezia infection or overgrowth (henceforth referred to as Malassezia otitis) in at least one ear canal at EFI1. A diagnosis of Malassezia otitis was accepted if there was additionally a record of: (vi) cytological evidence of Malassezia yeasts in aural discharge at EFI1 judged clinically relevant by the attending clinician; and (vii) absence of bacteria on cytological evaluation or culture of aural discharge at EFI1 and the visit immediately preceding EFI1. 通过搜索大型兽医转诊和教学医院(英国皇后动物医院)的临床管理系统，2007年1月1日至2018年9月10日转诊到皮肤科就诊的确诊为慢性耳病的患犬，这些犬进行全身麻醉下耳镜检查和耳道冲洗。此外，还利用“兽医监视系统”界面，在医院的患者记录系统中同时搜索了同一时期的“耳炎”和“马拉色菌”。对于在两次搜索中发现的所有犬只，然后分别搜索记录，以选择符合以下纳入标准的患犬:(i)耳病发作持续时间至少2个月;(ii)在麻醉下接受过至少一次(视频)耳镜引导下的耳道检查、冲洗和采样(耳道冲洗洗操作缩写，EFI;首次记录的耳道冲洗日期缩写为EFI1);(iii)在EFI1发生后四周内，曾接受耳部CT扫描;(iv)在EFI1后六周内至少复查一次;(v)在EFI1有至少一个耳道确诊有马拉色菌感染或过度增殖(之后称为马拉色菌耳炎)。如果有以下记录，则确诊为马拉色菌耳炎:(vi)由主治医生判断EFI1时耳分泌物细胞学检查中马拉色酵母菌具有临床相关性;(vii) EFI1和EFI1之前的就诊记录中在耳分泌物细胞学检查或细菌培养中未发现细菌。
For comparison of signalment data, a denominator population of chronic otitis cases was generated by identifying dogs seen at the referral hospital during the same period, with ”otitis” (VetCompass), having undergone a (video)otoscopy and CT scan and that did not otherwise match the study criteria. 为了对比临床症状数据，搜索同一时期在转诊医院就诊的“耳炎”(VetCompass)，并接受了(视频)耳镜和CT扫描的慢性耳炎病例是分母数据，除此之外不符合研究标准。
Data extraction and definitions 数据提取和定义 Data extracted from EFI1 and the visit preceding EFI1 case records included: signalment, age at onset of ear disease, duration of presenting episode of ear disease, CT findings and status of ear disease. Data extracted from subsequent visits included: number of EFI, status of ear disease, oral medicines prescribed, topical products prescribed, date of first documented absence of infection or overgrowth and date of the last visit (relevant to that episode of ear disease). 从EFI1和在EFI1之前就诊的病例记录中提取的数据包括:临床症状、耳病发病年龄、耳病发作持续时间、CT结果和耳病情况。从随后的复诊中提取的数据包括:EFI次数、耳病情况、口服用药、外部用药、首次记录无感染或过度增殖的日期以及最后一次复诊日期(与耳病发作相关)。
Otitis status at EFI1 was recorded as either MalOE or “MalOE with concurrent Malassezia OM” (MalOE/OM). Diagnosis of MalOE was assigned based upon recorded diagnosis of OE and an absence of middle ear pathological findings on CT imaging. A diagnosis of MalOE/OM required cytological detection of yeast microbes within debris aspirated directly from the middle ear, in the presence or absence of soft tissue attenuating material in the middle ear on CT imaging. If MalOE was associated with bacterial or sterile OM in the same ear, this ear was excluded from the study. EFI1的耳炎情况记录为MalOE或“MalOE伴马拉色菌OM”(MalOE/OM)。MalOE的诊断是基于OE的诊断记录和CT结果没有中耳病理变化。诊断MalOE/OM需要对直接从中耳抽吸耳垢进行细胞学检查发现酵母菌，CT的中耳检查是否存在软组织密度物质。如果MalOE伴有细菌，或同一耳是无菌OM，则将该耳排除在研究之外。
Medications administered before or after EFI1 were categorised as oral medicines (anti-inflammatory, antifungal or antibacterial) or topical products (medicinal ear drops and other ear solutions). Medicinal drops were further categorised as combination products (containing an antifungal, glucocorticoid and antibacterial agent), antifungalonly or glucocorticoid-only products. EFI1前后药物治疗分为口服药(抗炎、抗真菌或抗细菌)和外用药(药用滴耳液和其他耳液)。药物滴剂进一步分为复方产品(包括抗真菌、糖皮质激素和抗细菌药物)、单一抗真菌产品或单一糖皮质激素产品。
Resolution of MalOE was based on recorded clinician judgement in combination with either cytological absence or paucity of microbes.Time-to-resolution was calculated from the date of EFI1 until the date of the visit first documenting resolution. Ears in which resolution was not documented before or at the last recorded visit, were considered treatment failures. The study end was the date of the visit at which resolution was first documented or the date of the last relevant visit with the dermatology service. MalOE的治愈是基于临床医生记录的判断结合细胞学检查没有或少量微生物。从EFI1日期开始计算到首次记录治愈的日期为治愈时间。没有耳部治愈日期记录或最后复诊记录的病例，被认为是治疗失败。研究结束日期为首次记录治愈的就诊日期，或最后一次相关皮肤科就诊日期。
Statistical analysis 统计学分析 Pure-bred dogs were grouped by breed clades showing >50% bootstrap support, based on the breed cladogram of Parker et al. 2017.Data were analysed in SPSS v26 (SPSS Inc.; Chicago, IL, USA). The normality of data distribution was tested using the Shapiro–Wilk test. Spearman’s rank correlation coefficient was used to evaluate correlation between duration of ear disease and median time-to-resolution in MalOE cases. Odds ratios (OR) were calculated for risk factors for diagnosis of MalOE/OM and clinical outcomes in MalOE cases. Confidence levels were set at 95% and the chosen level of significance was P < 0.05. 根据Parker等人2017的品种分类图，根据显示>50%辅助程序支持的品种分类对纯种犬进行分组。使用SPSS v26进行数据分析。数据分布正态性采用Shapiro Wilk检验。在MalOE病例中，用Spearman秩相关系数评价耳病持续时间与中位时间-分辨率之间的相关性。计算MalOE/OM诊断的危险因素和MalOE病例的临床结局的优势比(OR)。置信标准设置为95%，选择的显著性水平为P<0.05。
Results 结果 Fifty-nine dogs met the inclusion criteria and contributed 82 ears with Malassezia otitis to the study. Figure 1 summarises the case inclusion process at the dog and ear levels, and reasons for exclusion. 59只犬符合纳入标准，共82只马拉色菌耳炎患耳纳入研究。图1总结了纳入的犬和耳部标准，以及排除原因。
Signalment and ear disease history 临床症状和耳病病史 Table 1 summarises signalment, age at onset of ear disease and duration of the presenting otitis episode of the study population. Breed clade data are further detailed in Supporting information, Table S1. In the denominator population (n = 306), the retriever (33 of 306, 11%) and spaniel (72 of 306, 24%) clades were highly represented; however, retrievers had over three-fold greater odds of matching the study criteria [OR 3.4, confidence interval (CI) 1.7,6.5; P = 0.0002). The sex and neuter status profile (Table 1) was similar to the denominator population. 表1总结了研究对象的临床症状、耳病发病年龄和耳炎发作持续时间。品种分类数据详见补充信息表S1。在分母数据(n = 306)中，寻回犬(33/306,11%)和猎犬(72/306,24%)具有很高的代表性;然而，寻回犬符合研究标准的几率高出三倍以上[OR 3.4，置信区间(CI) 1.7,6.5;P = 0.0002)。性别和绝育情况概况(表1)与分母数据相似。
Otitis status 耳炎情况 Of the 59 study dogs with a recorded diagnosis of Malassezia otitis in at least one ear, 34 (58%; CI 45%,69%) had bilateral disease irrespective of the type of infection in the contralateral ear, and 25 (42%; CI 31%,55%) had unilateral ear disease. Of the 34 dogs with bilateral ear disease, 23 of 34 had Malassezia otitis diagnosed in both ears (n = 46 ears) and 11 of 34 dogs had Malassezia otitis diagnosed in only one ear (n = 11 ears), with bacterial or mixed (bacterial plus Malassezia) infection in the contralateral ear. Overall, 23 dogs contributed both ears to the study and 36 dogs contributed one ear to the study (Figure 1). 在59例至少有一只耳朵被诊断为马拉色菌耳炎的研究中，不论对侧耳部感染类型如何，有34例(58%;CI 45%,69%)双耳患病，25例(42%;CI 31%，55%)单耳患病。双耳患病的34例中,23例双耳诊断为马拉色菌耳炎(n = 46只耳)和11例单耳诊断马拉色菌耳炎(n = 11只耳),另一患耳伴有细菌或混合菌感染(细菌+马拉色菌)。总的来说，23例犬双耳纳入研究，36例犬单耳纳入研究(图1)。
Fifty of 59 dogs with Malassezia otitis had a diagnosis of MalOE only, eight of 59 dogs had MalOE/OM, and one of 59 dogs had MalOE in one ear and MalOE/OM in the contralateral ear. In ears diagnosed with MalOE at EFI1, the tympanic membrane was recorded as partially visible or not visible in eight of 68 ears, opaque/thickened in 19 of 68 ears, and having a bulging pars flaccida in four of 68 ears and a small tear in one of 68 ears. 59例马拉色菌耳炎患犬中有50例诊断为仅MalOE, 59例犬中有8例有MalOE/OM, 59例犬中有1例有一只耳是MalOE和对侧耳是MalOE/OM。确诊患MalOE在EFI1时,68只耳中8只耳鼓膜记录部分可见或不可见,19只耳记录不透明/增厚,4只耳记录鼓膜松弛部凸出，1只耳记录鼓膜有小裂缝。
Nine of 59 dogs had at least one ear with MalOE/OM and contributed 14 of 82 (17%; CI 10%,27%) ears with MalOE/OM to the study. Of the nine dogs with middle ear disease, five had bilateral MalOE/OM, three had bacterial, mixed-microbial or sterile OM in the contralateral ear and one dog had MalOE in the contralateral ear (Table S2). 59例犬中有9例至少有一只耳有MalOE/OM, 在研究的82只耳中占14只耳(17%;CI 10%，27%)是MalOE/OM。在9只患犬有中耳炎，5只患犬为双侧MalOE/OM, 3只患犬为对侧耳细菌性、混合菌性或无菌性OM, 1只患犬为对侧耳MalOE(表S2)。
During either the visit preceding EFI1 or EFI1, neutrophils were identified in aural discharge in 24 of 68 (35%) ears with MalOE and four of nine ears with MalOE/ OM. 在EFI1或EFI1之前的就诊中，68只(35%)MalOE患耳中24只患耳和9只MalOE/ OM患耳中有4只患耳耳分泌物中发现了中性粒细胞。
Duration of ear disease of seven months or more (OR 1.68, CI 0.43,6.65; P = 0.23) and identification of neutrophils in aural discharge (OR 0.73, CI 0.21,2.59; P = 0.31) did not affect the odds of being diagnosed with MalOE/OM. 耳病持续时间7个月以上(or 1.68, CI 0.43,6.65;P = 0.23)和耳分泌物中中性粒细胞的鉴定(OR 0.73, CI 0.21,2.59;P = 0.31)不影响MalOE/OM的诊断几率。
Foreign bodies or mass lesions were not identified in any of the ears included in the study. Of those 51 dogs diagnosed with MalOE, 22 (43%; CI 30%,57%) dogs had pruritus or erythema at sites distant to the pinnae recorded at presentation or during the study. 研究中未发现任何耳朵有异物或肿块。在确诊MalOE的51只患犬中，有22只(43%;(CI 30%，57%)患犬在出现症状时或在研究过程中，出现在耳廓远端部位有瘙痒或红斑症状。
Medication and ear flush interventions 药物治疗和耳部冲洗操作 Median duration of time from first presentation at the hospital to EFI1 was 17 days (range 0–77 days). Table 2a summarises oral medicines and Table 2b medicinal ear drops prescribed to study dogs. 从首次就诊到EFI1的中位持续时间为17天(范围0-77天)。表2a总结了用于研究犬的口服药物和表2b总结的药用滴耳剂。
Before EFI1, 46 of 59 (78%) dogs received oral (methyl)prednisolone: either an average dose of 0.8 mg/ kg prednisolone once daily (range 0.32 to 1.17 mg/kg/day) or a comparable dose of methylprednisolone. Four of 59 (7%) dogs received oral itraconazole and 23 of 82 (28%) ears received topical antifungal treatment. 在EFI1之前，59只犬中有46只(78%)接受口服(甲基)泼尼松龙:或平均剂量0.8 mg/kg泼尼松龙每天一次(范围0.32至1.17 mg/kg/天)，或同等剂量的甲基泼尼松龙。59只犬中有4只(7%)接受了口服伊曲康唑治疗，82只耳中有23只耳(28%)接受了外用抗真菌治疗。
Owing to the low number of dogs with MalOE/OM, interventions for this group are not specifically reported here. 由于患有MalOE/OM的犬的数量较少，这里没有对这一组的操作进行具体报道。
Forty-six dogs (60 of 68 ears, 88%) with MalOE underwent one EFI, four dogs (six of 68 ears, 9%) underwent two EFIs and one dog (two of 68 ears, 3%) underwent three EFIs by the study end. Repeat EFIs were performed in cases where there was cytological evidence of persistent infection or accumulation of debris following EFI1, indicating lack of resolution. The duration was 28–91 days between the first and second EFI (four dogs), and 36 days between the second and third EFI (one dog). 在研究结束时，46只MalOE犬(68只犬中的60只，88%)接受了一次EFI, 4只犬(68只犬中的6只，9%)接受了两次EFI, 1只犬(68只犬中的2只，3%)接受了3次EFI。在EFI1后，如果细胞学检查显示持续感染或耳垢堆积，表明没有治愈，则进行重复EFI。第1-2次EFI(4只)持续时间为28-91天，第2-3次EFI(1只)持续时间为36天。
After EFI1, most dogs with MalOE still received an oral glucocorticoid and less than a third received oral itraconazole; however, almost all MalOE ears (64 of 68, 94%) received topical antifungal treatment. Combination ear drops were prescribed most commonly. 在EFI1后，大多数MalOE的犬仍然接受口服糖皮质激素，不到三分之一的犬接受口服伊曲康唑;然而，几乎所有MalOE耳朵(64 / 68,94%)接受外用抗真菌治疗。最常用的处方是复方滴耳剂。
Two dogs (three MalOE ears) received no topical antifungal therapy at any time yet did receive oral itraconazole: one had a suspected contact dermatitis to topical products and one would not tolerate topical therapy. Resolution of infection in those ears occurred at days 13, 27 and 27 of treatment post-EFI1. One dog (one MalOE ear) received no antifungal treatment and instead received oral prednisolone and an ear cleaning product after removal of a ceruminolith at EFI1. 两只犬(三只MalOE耳朵)在任何时候都没有接受外用抗真菌治疗，但接受了口服伊曲康唑:一只疑似外用产品接触性皮炎，另一只对外用治疗不耐受。在EFI1治疗后的第13、27和27天，这些耳朵的感染得到了解决。一只犬(MalOE的一只耳朵)没有接受抗真菌治疗，而是在EFI1清除耵聍后接受口服泼尼松龙和一种洗耳液管理。
Topical ear solutions other than medicinal ear drops (generally referred to as “ear cleaning products”) were used in just over half (35 of 68, 51%) of the ears with MalOE at some point during treatment; owing to the diversity of products and treatment protocols, these are not reported further. 治疗期间，MalOE治疗组中有超过一半(68/35,51%)的耳朵使用了除药用滴耳液外的外用耳液(一般称为“洗耳液”);由于产品和治疗方案的多样性，这些没有进一步报道。
Treatment outcomes for Malassezia otitis externa cases 马拉色菌外耳炎病例治疗效果 As a consequence of low numbers of MalOE/OM ears in this study, clinical outcomes and risk factors are reported for MalOE ears only. Table S2 lists the number of EFI and treatment outcomes for ears diagnosed with MalOE/OM. 由于本研究中MalOE/OM耳的数量较少，因此仅报道MalOE耳的临床效果和危险因素。表S2列出了被诊断为MalOE/OM的耳朵的EFI数目和治疗结果。
Sixty-two of 68 (91%) ears diagnosed with MalOE had a successful outcome with resolution of infection. At the time of resolution, 57 of 62 (92%) MalOE ears had no cytological evidence of yeast microbes and five of 62 (8%) had yeast numbers reported as “rare” (two of five), “rare/consistent with normal” (two of five) and “few/consistent with normal” (one of five) by the clinician. Neutrophils were recorded in five of 62 of ears at the time of clinical resolution, in the absence of yeast microbes. 68只确诊MalOE的耳朵中有62只(91%)感染治愈。治愈的时候,62只(92%)MalOE患耳中57只患耳细胞学检查没有酵母菌和5只患耳(8%)临床医生的酵母菌报告为“罕见”(5只中2只),“罕见/符合正常”(5只中2只)和“少量/符合正常”（5只中1只）。在没有酵母菌的情况下，62只患耳中有5只记录了中性粒细胞。
Median time-to-resolution was 27 days (range 7– 178 days) in MalOE cases. Of 62 of 68 MalOE ears with a successful outcome, 54 of 62 (87%) resolved after only one EFI. Seven of 62 MalOE ears were recorded to have infection resolved within two weeks of EFI1. In only two of these ears was the total treatment time, from the visit preceding EFI1 to resolution, less than four weeks (13 and 17 days, respectively). Of the six of 68 (9%) MalOE ears with an unsuccessful outcome, two ears were referred for surgical intervention and four ears were lost to follow-up. MalOE病例中位时间为27天(范围7 - 178天)。68例MalOE耳中62例成功治愈，54例(87%)在一次EFI后治愈。62只MalOE耳中有7只在EFI1治疗后两周内感染治愈。在这些耳朵中只有两个是总治疗时间，从EFI1之前就诊到治愈，不到4周(分别为13天和17天)。68例MalOE耳中有6例(9%)治疗失败，其中2例接受手术治疗，4例未复诊。
There was no significant correlation between duration of ear disease and median time-to-resolution (rs = 0.19). The presence of neutrophils in aural discharge (OR 0.51, CI 0.10,2.76; P = 0.22) and prescription of itraconazole (OR 0.88, CI 0.15,5.25; P = 0.45) did not affect the odds of having a successful outcome in ears with MalOE. 耳病持续时间与治愈时间中位值之间没有显著相关性(rs = 0.19)。耳分泌物中存在中性粒细胞(OR 0.51, CI 0.10,2.76;P = 0.22)和口服伊曲康唑(OR 0.88, CI 0.15,5.25;P = 0.45)，不影响MalOE患耳成功治疗的几率。
Discussion 讨论 In 1964, Spruell wrote that “The incidence of otitis externa is so high, and the distribution so widespread, that the spate of attention the problem has received during the last 10 years is fully justified”.Almost 60 years later, despite the development of multiple new ear products, this statement is still valid. Intervention trials with topical therapeutics for unspecified OE have reported success rates between 65% and 81%. The potential for chronic disease is highlighted by a report that 24% of dogs presenting for otitis had one or multiple recurrences following initial treatment with topical combination products. Reasons for incomplete or lack of resolution, or recurrence of otitis after a course of treatment, are likely to variably reflect treatment-related (effectiveness, frequency, duration and compliance) and ear disease-related (predisposing, primary, secondary and perpetuating) factors that can be difficult to address, particularly within the confines of a busy primary care practice environment. 1964年,Spruell写道:“外耳炎的发病率是如此之高,分布如此之广,以至于在过去10年里这个疾病完全有理由受到大量关注”。近60年后，尽管出现多种新的耳部产品,这句话仍然有效。对未明确OE进行外部治疗管理试验报告的成功率在65%到81%之间。一份报告强调了慢性疾病的可能性，报告显示24%的耳炎患犬在使用复方外用药物治疗后出现了一次或多次复发。经过一段治疗后耳炎不完全或没有缓解，或复发的原因各不相同，可能与治疗有关(有效性、频率、持续时间和依从性)以及与耳病病因有关(易感、原发、继发和持久)，特别是在繁忙的初级临床治疗环境中。
Although Malassezia frequently is found in combination with bacteria in canine OE, the present study was deliberately limited to treatment of otitis cases unresponsive to primary care and associated with Malassezia infection/overgrowth in the cytological absence of bacteria, to provide a preliminary clinical practice benchmark for this more defined clinical subset. 虽然马拉色菌经常在犬OE中与细菌同时发现，但目前的研究故意局限于对初级常规治疗无效的耳炎病例的治疗，伴有马拉色菌感染/过度增殖在细胞学检查和上没有细菌，为这个更明确的临床子集提供初步的临床实践基准。
This case series demonstrates that most (91%) cases of chronic Malassezia OE in dogs, unresponsive to primary care treatment, can be treated successfully with a medical treatment plan, typically within four weeks (median 27 days) of one (87%) ear flush intervention. In the few cases where resolution of infection occurred faster, it is possible that significant response occurred before the scheduled ear flush or the previous treatment history was inaccurate. 该病例分析表明，大多数(91%)对初级常规治疗无效的犬慢性马拉色菌OE病例可通过药物计划成功治疗，通常在一次(87%)耳道冲洗后的四周(中位数27天)内即可成功治疗。在少数感染治愈较快的病例中，可能在进行耳部冲洗之前临床症状就得到治愈，或者之前治疗不准确。
A notable feature of this case series was that medical management protocols routinely consisted of an initial two- to three-week treatment period before EFI1, during which time most dogs received oral prednisolone and no topical or oral antifungal treatment. Early therapy was concentrated more on reversing soft tissue changes secondary to inflammation than specifically addressing the Malassezia overgrowth/infection. This also may be explained by low clinician confidence in a topical mode of delivery due to ear canal occlusion/stenosis or patient aversion to treatment or therapeutic caution until the extent of ear pathological findings and type of infection were known. After EFI1, prescription of antifungal ear drops to most dogs indicates that impediments to topical therapy were deemed less significant at that point. 该病例分析的一个显著特征是，药物管理方案通常包括EFI1之前的2 - 3周初始治疗期，在此期间，大多数犬只接受口服泼尼松龙，而不接受外用或口服抗真菌治疗。早期治疗更多地集中于扭转炎症继发的软组织变化，而不是专门处理马拉色菌过度增殖/感染。这也可以解释为，在了解耳部病理结果和感染类型之前，由于耳道闭塞/狭窄或患犬治疗不配合或谨慎治疗，临床医生对外用药形式缺乏信心。在EFI1之后，对大多数犬使用抗真菌耳滴剂表明，此时外部治疗好像不那么有难度。
By comparison, less than a third of cases were prescribed oral itraconazole after a diagnosis of MalOE, perhaps as a result of clinician concerns over the ability of the drug to achieve effective concentrations in the ear canal. The addition of oral itraconazole to the treatment regimen, however, did not affect overall odds of treatment success in these MalOE cases. A successful outcome also was recorded for two dogs with MalOE prescribed oral itraconazole in the absence of antifungal ear drops. However, there is limited benefit in drawing conclusions from such low treatment numbers. 相比之下，不到三分之一的病例在确诊为MalOE后服用了伊曲康唑，这可能是因为临床医生担心药物在耳道内达到有效浓度的能力。然而，在这些MalOE病例中，在治疗方案中加入口服伊曲康唑并不影响总的治疗成功概率。在没有使用抗真菌滴耳液的情况下，也记录了有两例MalOE患犬通过口服伊曲康唑有成功疗效。然而，从如此低的治疗数量中得出结论的优势有限。
The management priority for the cases in this series at the time of entering the authors’ care was the chronic ear pathological findings. Oral glucocorticoids (or ciclosporin) and topical glucocorticoids used to reverse ear pathological findings can also be expected to have controlled primary inflammatory (allergic) ear disease, where present, and thus contributed to treatment success. In the authors’ practice, resolution of chronic MalOE typically is followed by measures to identify and address primary causes of otitis, and other strategies to prevent recurrence of infections. This aspect of ear disease management was not within the remit of this study, yet it was noted that nearly half of the dogs showed evidence of an allergic phenotype during their ear disease management. This is within the lower range of figures reported previously, and likely to represent an underestimate as a consequence of masking of signs during treatment. There is a current lack of (detailed) evidence on the effects of the nature of primary ear disease and of preventive management strategies on the long-term outcome of canine otitis. 本病例分析在到作者的医院就诊时，是慢性耳部病理表现。口服糖皮质激素(或环孢素)和外用糖皮质激素可逆转耳病理表现，也可预期控制原发炎性(过敏性)耳病，因此有助于成功治疗。在作者的医院中，慢性MalOE的解决通常是在确定和管理耳炎的原发病因之后，以及其他防止感染复发的策略。这方面的耳病管理不在本研究的范围内，但值得注意的是，近一半的犬在其耳病管理期间证明是过敏症表现。这在以前的报告中属于较小范围，可能是由于在治疗期间掩盖了症状而被低估的结果。目前缺乏(详细的)证据表明，原发耳病的性质和预防性管理策略对犬耳炎的长期预后的影响。
Otitis cases in this study are unlikely to represent the wider population of dogs with chronic Malassezia otitis, in view of selection bias inherent to a referral service and for dogs generally amenable to home treatment. However, in terms of age profile and unilateral versus bilateral otitis presentation, the cases in this study match other studies of chronic otitis and also field studies that have not specifically enrolled chronic cases. 本研究中的耳炎病例不太可能代表更大数量的慢性马拉色菌耳炎患犬，这是由于转诊服务固有的选择偏向，以及犬通常更多在家治疗。然而，在年龄和单侧与双侧耳炎的表现方面，本研究中的病例与其他慢性耳炎的研究以及没有专门纳入慢性病例的现场研究相匹配。
Together, spaniel and retriever breeds accounted for over half of the affected dogs in this study and also those in the hospital denominator population with otitis, similar to recent findings from a European otitis treatment intervention study.However, retrievers had over three times the odds of matching the study criteria, perhaps reflecting a relative predisposition to Malassezia otitis over other types of ear infections within this breed clade or higher odds of retrievers over spaniels being diagnosed with allergic skin disease. 在这项研究中，猎犬和寻回犬占患犬一半以上，还有那些在医院的代表性易患耳炎的犬种，这与最近一项欧洲耳炎治疗管理研究的发现相似。然而，寻回犬符合研究标准的几率是猎犬的三倍多，这可能反映了在这个品种中，与其他类型的耳感染相比，寻回犬更容易患马拉色菌耳炎，或者被诊断为过敏性皮肤病的几率高于猎犬。
In around one fifth of affected ears in this study, concurrent Malassezia OM was diagnosed based upon otoscopic findings and sampling of middle ear content. This procedure carries the potential for iatrogenic contamination of yeast from the ear canal into the tympanic cavity and thereupon false diagnosis of MalOE/OM. The frequency of MalOE/OM in the present study, however, is comparable to reports of OM diagnosed in dogs with undefined, chronic OE using CT and MRI imaging. However, both imaging modalities may fail to diagnose cases of early OM when there are only minor pathological findings in the tympanic cavity. It is notable that only four of 14 ears judged by the clinician to have MalOE/OM in this study, based on video-otoscopy and bulla lavage, had evidence of soft tissue attenuating material in the tympanic bulla on CT imaging. Integrity of the tympanic membrane was not a reliable indicator for status of middle ear disease (as proposed by Cole in 1998) and neither was absence of neurological signs or duration of ear disease. It would seem that a multimodal diagnostic approach may be required to investigate the involvement of the middle ear in cases of chronic otitis. 在本研究中，约五分之一的患耳中，同时患有马拉色菌OM是根据耳镜检查结果和中耳内容物取样诊断的。这种方法可能会导致酵母菌从耳道进入鼓室造成医源性污染，从而导致MalOE/OM的误诊。然而，在本研究中MalOE/OM的频率与使用CT和MRI成像诊断未明确的慢性OE患犬，确诊OM的报道相当。但是，这两种影像检查可能无法诊断早期OM的病例，即当鼓室只有轻微的病理变化时。值得注意的是，在本研究中，通过视频耳镜和鼓泡灌洗，临床医生判断为MalOE/OM的14只患耳中，只有4只在CT图像上有鼓室大泡软组织密度的证据。鼓膜的完整性并不是中耳疾病情况的可靠指标(Cole在1998年提出的)，没有神经学临床症状和耳病的持续时间也不是一个可靠的指标。在慢性耳炎病例中，似乎需要一种多模式诊断方法来研究中耳的患病情况。
This retrospective study documents a high success rate in the resolution of cases of chronic canine Malassezia OE, previously unresponsive to primary care, with a well-staged and intense medical treatment plan. It further shows that clinicians should suspect concurrent Malassezia OM in around a fifth of affected ears. 这项回顾性研究证明，在初级常规治疗无效的慢性犬马拉色菌OE病例中，通过明确分期和密切药物治疗计划，有很高的成功率。它进一步表明，临床医生应该怀疑大约1/5的患耳中同时存在马拉色菌OM。
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发表于 2021-10-29 20:38:16
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