兽研摘要
背景
过敏性外耳炎在犬中常见，复发可能导致反复就诊和抗菌药物使用。关于主动局部糖皮质激素维持治疗的长期数据有限。
目的
描述接受主动氢化可的松醋丙酸酯维持治疗的过敏性外耳炎患犬12个月内的复发频率，并比较连续用药日与非连续用药日方案的差异。
方法
回顾性审查了客户-owned犬被开具氢化可的松醋丙酸酯耳喷剂的医疗记录。维持治疗在临床和细胞学缓解后开始。仅纳入确认继续用药、合并过敏管理稳定且具有完整12个月结局数据的犬。复发定义为需要兽医检查、细胞学检查和额外耳部治疗的外耳炎复发。犬按方案分组：方案1，每周连续两天；方案2，每周非连续两天。使用Fisher精确检验和Mann–Whitney U检验比较结局。
结果
共纳入71只犬；方案1组36只，方案2组35只。在12个月内，50/71只犬（70.4%）无复发，12/71只（16.9%）复发一次，9/71只（12.7%）多次复发。方案1组9/36只犬（25.0%）和方案2组12/35只（34.3%）发生至少一次复发（p = 0.443）。多次复发分别发生于2/36只（5.6%）和7/35只（20.0%）犬（p = 0.085）。两种方案之间的复发次数无显著差异（p = 0.290）。
结论
大多数犬在主动氢化可的松醋丙酸酯维持治疗期间无复发或仅复发一次。两种方案之间未检测到统计学显著差异，但不能得出等效性或非劣效性结论。
关键词：过敏、犬、氢化可的松醋丙酸酯、外耳炎、复发
在71只临床和细胞学缓解后接受主动氢化可的松醋丙酸酯维持治疗的过敏性外耳炎患犬中，70.4%无复发，87.3%在固定12个月观察期内无复发或仅复发一次。维持方案之间未检测到统计学显著差异；然而，该研究并非旨在证明方案之间的等效性或非劣效性。
1. 引言
外耳炎是犬中常见且具有临床重要性的疾病。在过敏性犬中，外耳道炎症可能作为疾病的原发表现出现，可能伴随更广泛的皮肤体征，或在其他部位瘙痒明显控制后持续存在。一旦炎症建立，耳道微环境的变化有利于耵聍积聚和继发性酵母菌或细菌过度生长，反复发作可能促进慢性结构改变，进一步使长期控制复杂化（Nuttall 2023；Rosser 2004）。
因此，过敏性外耳炎的管理不仅限于治疗活动性感染。控制潜在的炎症成分对于减少复发、限制反复使用抗菌药物和防止向慢性耳道改变进展至关重要。这一概念与犬特应性皮炎的更广泛管理方法一致，即在缓解后主动进行抗炎治疗可能减少过敏性发作，而不是等待复发发生（Lourenço et al. 2016；Olivry et al. 2015）。
氢化可的松醋丙酸酯是一种非卤化二酯糖皮质激素，开发用于局部使用。其药理学特征旨在提供局部抗炎活性且全身暴露有限，先前在犬特应性皮炎中的研究报告了短期使用时的临床疗效且未检测到肾上腺抑制（Nam et al. 2012；Nuttall et al. 2009）。最近，氢化可的松醋丙酸酯耳喷剂已在红斑-耵聍性外耳炎患犬中进行了评估，短期治疗改善临床体征的效果与含抗菌药物的复方产品相似（Rigaut et al. 2024）。长期回顾性数据也支持其作为慢性或复发性非感染性外耳炎反应性和主动性管理的一部分（Lorente-Mendez and Alonso-Miguel 2025）。
然而，在临床实践中，维持方案并不统一。一些临床医生每周开具连续两个治疗日，而另一些则使用非连续日。这种差异的相对重要性尚不清楚。本回顾性多中心研究的主要目的是描述过敏性外耳炎患犬在临床和细胞学缓解后接受主动氢化可的松醋丙酸酯维持治疗、在固定12个月观察期内的复发频率。次要目的是比较连续用药日与非连续用药日维持方案之间的复发频率，不假设方案之间等效。
2. 材料与方法
2.1. 研究设计与报告
这是一项回顾性多中心观察性研究，研究对象为客户-owned过敏性外耳炎患犬，在固定12个月观察期内接受主动局部氢化可的松醋丙酸酯维持治疗。设计和报告遵循STROBE观察性研究建议（von Elm et al. 2007）。
分析单位为犬。当双耳均受累时，根据维持治疗前记录的较严重或临床相关的耳炎表型对犬进行分类。
2.2. 病例选择
审查病历以确定诊断为过敏性外耳炎并接受氢化可的松醋丙酯0.584 mg/mL耳喷雾溶液（Cortotic；Virbac，Carros，法国）主动性维持治疗的犬。过敏性外耳炎由主治临床医生根据相符的病史、临床、细胞学和耳镜检查结果、继发感染的排除或治疗，以及过敏性皮肤病的 presence 或怀疑（包括特应性皮炎、食物过敏或两者兼有）进行诊断。诊断要求排除耳炎的其他原发原因，包括临床相关时的体外寄生虫和异物，并控制继发性细菌或酵母菌感染。跳蚤侵染和跳蚤过敏性皮炎被排除或控制。食物过敏在临床指示时通过消除饮食和口服食物激发试验进行评估，犬特应性皮炎在排除相关鉴别诊断后使用公认的临床标准进行诊断。
仅将通过主人电话随访确认继续治疗且具有固定12个月观察期完整信息的犬纳入最终分析。维持治疗仅在活动性耳炎发作达到临床和细胞学缓解后开始。伴随的过敏管理，包括全身性止痒或抗炎治疗、过敏原特异性免疫治疗和饮食，在12个月观察期内必须保持不变。如果治疗未继续、无法确认继续治疗、无法获得更新的复发信息或随访短于12个月，则排除犬。如果维持方案改变、氢化可的松醋丙酯未按处方给药、随访期间开始、停止或改变伴随过敏治疗或饮食，或无法获得完整的12个月结局数据，也排除犬。
2.3. 数据收集
从病历中提取的数据包括信号ment、诊断、维持治疗前耳炎的侧别、耳炎的临床类型、细胞学发现、维持方案、记录的伴随过敏管理、随访信息以及研究期间的复发次数。进行主人电话随访以确认犬是否继续维持治疗并更新复发信息。未获得回应时，犬被排除在最终分析之外。因此，最终队列中纳入的所有71只犬均确认继续治疗、更新了复发信息并具有完整的12个月随访。
2.4. 治疗方案
所有纳入的犬均接受主动性氢化可的松醋丙酯维持治疗。根据处方方案将犬分为两组。方案1包括连续两天给药。方案2包括每周两个非连续日给药，间隔至少两个无治疗日。治疗分配非随机化，反映主治临床医生的判断和常规实践。
维持治疗期间，临床稳定的犬每周接受一次基于氯己定的耳道清洁剂，在氢化可的松醋丙酯给药前24小时使用。无论氢化可的松醋丙酯是连续两天还是两个非连续日给药，该耳道清洁方案均为每周一次。
进入维持期前用于实现缓解的治疗以及复发时使用的救援治疗，根据耳镜检查和耳细胞学选择。马拉色菌过度生长使用硝酸咪康唑、硫酸多粘菌素B和醋酸泼尼松龙的局部复方制剂治疗，八滴，每日两次，连用14天，联合基于氯己定的耳道清洁剂每日一次，连用14天。球菌性细菌感染，细胞学定义为球菌伴有中性粒细胞性炎症和/或细胞内细菌，使用氢化可的松醋丙酯、硝酸咪康唑和硫酸庆大霉素的局部复方制剂治疗，一泵，每日一次，连用14天，联合氯己定/Tris-EDTA耳溶液每日一次，连用14天。杆状细菌感染和混合感染（杆菌和球菌）使用马波沙星、克霉唑和醋酸地塞米松的局部复方制剂治疗，八滴，每日一次，连用14天，联合氯己定/Tris-EDTA耳溶液每日一次，连用14天。当诊断为假单胞菌属感染时，在局部恩诺沙星/地塞米松/氯化钠溶液每日一次前30分钟使用N-乙酰半胱氨酸/Tris-EDTA溶液2 mL每日一次；这些病例还接受口服泼尼松龙1 mg/kg每日一次，连用14天。需要不同救援方案或改变维持或过敏管理的犬未保留在最终分析中。
2.5. 结局指标
主要结局是在12个月观察期内维持治疗期间至少发生一次复发。复发定义为需要兽医检查、细胞学确认和额外耳部治疗的外耳炎复发发作。次要结局是发生多次复发（定义为两次或以上复发）以及观察期内的总复发次数。由于所有犬均被观察了整整12个月，每只犬的总复发次数等同于每犬年复发率。
2.6. 统计分析
采用描述性统计总结群体特征和治疗结局。连续变量以中位数和范围报告。分类变量以数量和百分比报告。比较不同治疗方案之间的信号特征和基线耳炎特征。连续变量采用Mann–Whitney U检验进行比较。分类变量采用Fisher确切检验（用于2×2表）或卡方检验（用于较大的列联表）进行比较。至少一次复发和多次复发的犬的比例在方案间采用Fisher确切检验进行比较。复发次数采用Mann–Whitney U检验进行比较。计算方案2与方案1相比的相对危险度和95%置信区间。统计显著性设定为p < 0.05。由于方案间的比较是次要性和探索性的，结果的解释侧重于效应量、置信区间和临床合理性，而非仅依赖p值。未预先设定非劣效性或等效性界值，且本研究并非作为非劣效性或等效性试验设计或具有相应检验效能。
3. 结果
3.1. 研究群体
筛选了104只被开具醋酸氢化可的松耳喷雾剂用于过敏性外耳炎主动性管理的犬的医疗记录。71只犬符合最终纳入标准。33只犬被排除，原因是未开始治疗或未按规定期限继续治疗、维持方案或伴随过敏管理发生变化、主人随访无法确认所需信息，或无法获得完整的12个月结局数据。所有犬均接受了醋酸氢化可的松耳喷雾剂治疗。所有纳入的犬均有12个月随访，且通过主人电话随访确认继续执行了规定的维持方案。36只犬接受方案1，35只犬接受方案2。研究群体和治疗方案分布总结于表1。年龄在组间存在差异：接受方案1的犬中位年龄为5岁（范围1–14），而接受方案2的犬中位年龄为7岁（范围1–15；p = 0.041）。体重和性别分布在组间无显著差异（分别为p = 0.324和p = 0.196；表1）。共涉及46个品种。最常见的品种为法国斗牛犬（8/71）、英国/美国可卡犬（8/71）、拉布拉多寻回犬（6/71）、金毛寻回犬（3/71）和马尔济斯犬（3/71）。
研究群体及治疗方案间信号特征数据的比较。
注：除非另有说明，数据以n（%）表示。p值来自连续变量的Mann–Whitney U检验和性别分布的卡方检验。
3.2. 基线耳炎特征
在维持治疗前，外耳炎为双侧的55/71只犬（77.5%），单侧的16/71只犬（22.5%）。最常见的基线临床类型为耵聍性耳炎，其次为红斑性、化脓性和溃疡性耳炎。基线细胞学最常见鉴定为马拉色菌属；17/71只犬（23.9%）未记录到微生物。基线耳炎特征总结于表2。基线侧别、临床类型、细胞学类别和量评分在方案间无显著差异（表2）。
缓解诱导和治疗前基线耳炎特征及方案间比较。
注：对于双耳临床类型或细胞学发现不同的犬，在适用情况下采用较严重的临床类型进行分类。p值来自侧别的Fisher确切检验、临床类型和细胞学类别的卡方检验以及量评分的Mann–Whitney U检验。
3.3. 总体复发结局
在12个月观察期内，50/71只犬（70.4%；95% CI，58.4–80.7%）无复发，21/71只犬（29.6%；95% CI，19.3–41.6%）至少有一次复发。12只犬（16.9%；95% CI，9.0–27.7%）有一次复发，而9只犬（12.7%；95% CI，6.0–22.7%）有多次复发。总体复发结局及方案间比较总结于表3。总复发次数为39次，覆盖71犬年，相当于0.55次复发/犬年。
固定12个月观察期内总体及按维持方案分组的复发结局。
注：方案1 = 连续两天给药；方案2 = 非连续日给药。RR = 方案2与方案1相比的相对危险度；CI = 置信区间。由于所有犬均被观察12个月，每只犬的复发次数等同于每犬年复发次数。分类结局采用Fisher确切检验，复发次数采用Mann–Whitney U检验。
3.4. 维持方案间的比较
在接受方案1的36只犬中，有9只（25.0%；95% CI，12.1–42.2%）至少发生一次复发；在接受方案2的35只犬中，有12只（34.3%；95% CI，19.1–52.2%）至少发生一次复发。该差异无统计学意义（方案2相对于方案1的相对危险度为1.37；95% CI，0.66–2.84；p = 0.443）。接受方案1的36只犬中有2只（5.6%；95% CI，0.7–18.7%）发生多次复发，接受方案2的35只犬中有7只（20.0%；95% CI，8.4–36.9%）发生多次复发。该数值差异未达到统计学显著性（相对危险度，3.60；95% CI，0.80–16.15；p = 0.085）。方案1的复发总数为14次，方案2为25次。由于每只犬贡献了一年的观察期，方案1的复发率为0.39次/犬年，方案2为0.71次/犬年。两组的复发次数中位数均为0，且两种方案之间的复发次数无显著差异（p = 0.290；表3）。
4. 讨论
本研究描述了过敏性外耳炎患犬在达到临床和细胞学缓解后进入氢化可的松醋丙酸酯主动性维持治疗，在12个月观察期内的复发频率。在该验证队列中，70.4%的犬无复发，另有16.9%的犬仅复发一次。这些发现与Lorente‐Méndez和Alonso‐Miguel近期开展的回顾性研究大体一致，该研究将氢化可的松醋丙酸酯用于非感染性慢性或复发性外耳炎的反应性和主动性管理，79.1%的治疗耳在平均202.6天的随访期内保持无复发（Lorente‐Mendez and Alonso‐Miguel 2025）。直接比较存在局限性，因为该研究分析的是耳而非犬，纳入的是慢性或复发性非感染性外耳炎而非特指过敏性外耳炎，使用了根据严重程度调整的治疗方案，且随访期长短不一。相比之下，本研究以犬为分析单位，要求维持治疗前达到临床和细胞学缓解，并在固定的12个月观察期内评估复发。尽管如此，两项研究均支持使用持续局部抗炎维持治疗来预防复发性过敏性外耳炎的复发。
连续两天给药的犬在数值上复发次数少于非连续日给药的犬，尤其是多次复发。然而，该发现必须谨慎解读，因为两种维持方案之间未检测到统计学显著差异。本研究并非设计为非劣效性或等效性试验，也未按此进行把握度计算，且犬和复发事件数量较少，限制了检测方案间真实差异的能力。连续日给药组观察到的较低复发频率应视为产生假设，需要在样本量充足的前瞻性对照研究中加以评估。
方案间的比较还受到研究观察性本质的限制。治疗分配未随机化，反映了常规临床实践。尽管比较了组间基线特征，但既往复发模式、耳道变化、主人依从性或临床医生偏好等方面未测量的差异可能影响了维持方案的选择。此外，方案2的犬比方案1的犬年龄更大，不能排除年龄作为潜在混杂因素。因此，方案比较应解读为探索性而非验证性。
结果不应被解读为维持治疗单独即可控制过敏性外耳炎所有方面的证据。主动性局部治疗针对耳道的炎症成分，但过敏性疾病仍为多因素性。尽可能避免过敏原、控制体外寄生虫、管理存在的食物过敏、适当治疗继发感染、有指征时进行耳道清洗以及全身性抗炎或止痒治疗均可能影响结局。既往在犬特应性皮炎中的研究表明，氢化可的松醋丙酸酯可减轻皮肤病变和瘙痒（Nam et al. 2012；Nuttall et al. 2009；Nuttall et al. 2012），与全身治疗联合可能有助于在全身治疗减量时防止恶化（Takahashi et al. 2021）。
更广泛的主动性治疗概念也得到Lourenço等（2016）的支持，该研究中间歇性氢化可的松醋丙酸酯喷雾延长了犬特应性皮炎的复发时间，尽管该研究为前瞻性、安慰剂对照，且聚焦于皮肤病变而非外耳炎。
在本研究中，仅当合并的过敏管理在12个月观察期内保持稳定时，犬才被保留在最终分析中。这包括适用的全身性止痒或抗炎治疗、过敏原特异性免疫治疗和饮食。该标准旨在减少重大治疗变化对耳炎复发频率的影响。然而，合并的过敏治疗未随机化或标准化，不能排除其对复发风险的可能影响。
本分析仅纳入确诊继续遵循既定维持方案的犬只，其伴随过敏管理稳定且具备完整的12个月结局信息，因此能更清晰地估计实际接受预期维持方案的犬只中复发频率。然而，这一选择也引入了选择偏倚。停止治疗、错误使用产品、改变过敏治疗、记录不完整或无法联系的犬只被排除在外。因认为疗效不足而停止治疗的犬只，或因病情稳定而由主人决定停止治疗的犬只，因此未出现在最终队列中。因此，结果应解释为经验证依从队列中的结局，而非对所有最初被开具醋酸氢化可的松维持治疗的犬只的意向性治疗估计。
复发的定义比仅由主人报告的复发更为严格，需要兽医检查、耳部细胞学检查及额外的耳部治疗。然而，回顾性复发评估仍易受回忆偏倚和记录偏倚的影响。由主人在无兽医检查的情况下处理的轻微发作，或在其他地方治疗但记录不完整的发作，可能被遗漏。确切的复发日期未能一致获取，因此无法进行首次复发时间分析。这一局限性部分被固定的12个月观察期所缓解，该观察期允许比较组间复发频率和每犬年复发率，但无法比较复发时间。依从性由主人报告确认，但未进行客观测量。最后，本研究没有未治疗的对照组；因此，它不能证明醋酸氢化可的松维持治疗导致了低复发频率，只能说明在稳定管理条件下继续预期方案的犬只中复发频率较低。
5. 结论
在这项回顾性现场队列中，患有过敏性外耳炎并在临床和细胞学缓解后进入主动性醋酸氢化可的松维持治疗的犬只，大多数在固定的12个月观察期内无复发或仅复发一次。连续日与非连续日维持方案之间未检测到统计学显著差异；然而，本研究的设计和把握度并非用于证明方案间的等效性或非劣效性。这些发现支持进一步前瞻性评估主动性局部抗炎维持治疗作为过敏性外耳炎长期管理的一部分，包括对维持方案进行充分把握度的比较以及标准化的复发时间评估。
作者贡献
Elisa Maina：概念化；方法学；调查；形式分析；监督；项目管理；写作——初稿；写作——审阅与编辑。Rigert Jasmine Chantale：调查；数据管理；写作——审阅与编辑。Carlotta Filippini：调查；数据管理；写作——审阅与编辑。Regula Cao：调查；数据管理；验证；写作——审阅与编辑。Ana Oliveira：验证；写作——审阅与编辑。
资助
作者无内容需要报告。
伦理声明
作者确认已遵守《兽医医学与科学》的伦理政策。这是一项对客户所有犬只临床记录的回顾性审查，这些犬只作为常规兽医护理的一部分接受了获批用于耳部给药的商业化兽药产品治疗。未为研究目的进行任何操作，根据适用的机构和国家标准，无需正式伦理批准。
患者/客户知情同意声明
已获得客户知情同意，用于作为常规兽医护理一部分进行的诊断和治疗操作。进行了主人电话随访以确认治疗继续和临床结局。数据在分析前已匿名化。
利益冲突
作者声明无利益冲突。
数据可用性声明
支持本研究结果的数据不公开可用，因为它们包含客户所有动物的机密临床信息。匿名数据可根据合理请求从通讯作者处获取，并须符合适用的机构和数据保护要求。
查看英文原文▾
ABSTRACT
Background
Allergic otitis externa is common in dogs and recurrence may lead to repeated consultations and antimicrobial use. Long‐term data on proactive topical corticosteroid maintenance are limited.
Objectives
To describe 12‐month relapse frequency in dogs with allergic otitis externa receiving proactive hydrocortisone aceponate maintenance therapy and compare consecutive‐day and non‐consecutive‐day schedules.
Methods
Medical records of client‐owned dogs prescribed hydrocortisone aceponate ear spray were retrospectively reviewed. Maintenance started after clinical and cytological remission. Only dogs with confirmed continuation, stable concomitant allergy management and complete 12‐month outcome data were included. Relapse was defined as recurrent otitis externa requiring veterinary examination, cytology and additional otic treatment. Dogs were grouped by schedule: Protocol 1, two consecutive days; and Protocol 2, two non‐consecutive days weekly. Outcomes were compared using Fisher exact and Mann–Whitney U tests.
Results
Seventy‐one dogs were included; 36 in Protocol 1 and 35 received Protocol 2. During 12 months, 50/71 dogs (70.4%) had no relapse, 12/71 (16.9%) had one relapse and 9/71 (12.7%) had multiple relapses. At least one relapse occurred in 9/36 dogs (25.0%) in Protocol 1 and 12/35 (34.3%) receiving Protocol 2 ( p = 0.443). Multiple relapses occurred in 2/36 (5.6%) and 7/35 (20.0%) dogs, respectively ( p = 0.085). Relapse counts did not differ significantly between protocols ( p = 0.290).
Conclusions
Most dogs had no relapse or only one relapse during proactive hydrocortisone aceponate maintenance. No statistically significant difference was detected between schedules, but equivalence or non‐inferiority cannot be concluded.
Keywords: allergy, dogs, hydrocortisone aceponate, otitis externa, recurrence
In 71 dogs with allergic otitis externa receiving proactive hydrocortisone aceponate maintenance therapy after clinical and cytological remission, 70.4% had no relapse and 87.3% had no relapse or only one relapse during a fixed 12‐month observation period. No statistically significant difference was detected between maintenance schedules; however, the study was not designed to demonstrate equivalence or non‐inferiority between protocols.
1. Introduction
Otitis externa is a common and clinically important condition in dogs. In allergic dogs, inflammation of the external ear canal may occur as a primary manifestation of disease, may accompany more generalised cutaneous signs, or may persist after apparent control of pruritus elsewhere. Once inflammation is established, changes in the ear canal microenvironment favour cerumen accumulation and secondary yeast or bacterial overgrowth, and repeated episodes may promote chronic structural changes that further complicate long‐term control (Nuttall 2023 ; Rosser 2004 ).
For this reason, management of allergic otitis externa is not limited to treatment of active infection. Control of the underlying inflammatory component is central to reducing recurrence, limiting repeated antimicrobial use and preventing progression towards chronic ear canal changes. This concept is consistent with the wider approach to canine atopic dermatitis, in which proactive anti‐inflammatory treatment after remission may reduce allergic flares rather than waiting for relapse to occur (Lourenço et al. 2016 ; Olivry et al. 2015 ).
Hydrocortisone aceponate is a non‐halogenated diester glucocorticoid developed for topical use. Its pharmacological profile is intended to provide local anti‐inflammatory activity with limited systemic exposure, and previous studies in canine atopic dermatitis reported clinical efficacy without detectable adrenal suppression during short‐term use (Nam et al. 2012 ; Nuttall et al. 2009 ). More recently, hydrocortisone aceponate ear spray has been evaluated in dogs with erythemato‐ceruminous otitis externa, where short‐course treatment improved clinical signs similarly to an antimicrobial‐containing combination product (Rigaut et al. 2024 ). Long‐term retrospective data also support its use as part of reactive and proactive management of chronic or recurrent non‐infectious otitis externa (Lorente‐Mendez and Alonso‐Miguel 2025 ).
In clinical practice, however, maintenance schedules are not uniform. Some clinicians prescribe two consecutive treatment days each week, whereas others use non‐consecutive days. The relative importance of this difference is unknown. The primary objective of the present retrospective multicentre study was to describe relapse frequency over a fixed 12‐month observation period in dogs with allergic otitis externa receiving proactive hydrocortisone aceponate maintenance therapy after clinical and cytological remission. A secondary objective was to compare relapse frequency between consecutive‐day and non‐consecutive‐day maintenance protocols, without assuming equivalence between schedules.
2. Materials and Methods
2.1. Study Design and Reporting
This was a retrospective multicentre observational study of client‐owned dogs with allergic otitis externa receiving proactive topical hydrocortisone aceponate maintenance therapy over a fixed 12‐month observation period. The design and reporting were guided by STROBE recommendations for observational studies (von Elm et al. 2007 ).
The unit of analysis was the dog. When both ears were affected, the dog was classified according to the more severe or clinically relevant otitis phenotype recorded before maintenance therapy.
2.2. Case Selection
Medical records were reviewed to identify dogs diagnosed with allergic otitis externa and prescribed proactive maintenance therapy with hydrocortisone aceponate 0.584 mg/mL ear spray solution (Cortotic; Virbac, Carros, France). Allergic otitis externa was diagnosed by the attending clinician on the basis of compatible history, clinical, cytological and otoscopic findings, exclusion or treatment of secondary infection, and the presence or suspicion of allergic skin disease, including atopic dermatitis, food allergy or both. The diagnosis required exclusion of other primary causes of otitis, including ectoparasites and foreign bodies where clinically relevant, together with control of secondary bacterial or yeast infection. Flea infestation and flea‐allergy dermatitis were excluded or controlled. Food allergy was assessed when clinically indicated with an elimination diet and oral food challenge, and canine atopic dermatitis was diagnosed using accepted clinical criteria after exclusion of relevant differential diagnoses.
Only dogs for which treatment continuation was confirmed by owner telephone follow‐up and for which complete information for a fixed 12‐month observation period was available were included in the final analysis. Maintenance therapy was started only after clinical and cytological remission of the active otitis episode had been achieved. Concomitant allergy management, including systemic antipruritic or anti‐inflammatory treatment, allergen‐specific immunotherapy and diet, had to remain unchanged during the 12‐month observation period. Dogs were excluded if treatment had not been continued, if continuation could not be confirmed, if updated relapse information could not be obtained, or if follow‐up was shorter than 12 months. Dogs were also excluded if the maintenance schedule was changed, if hydrocortisone aceponate was not administered as prescribed, if concomitant allergy treatment or diet was initiated, discontinued or changed during follow‐up, or if complete 12‐month outcome data were not available.
2.3. Data Collection
Data extracted from medical records included signalment, diagnosis, laterality of otitis before maintenance therapy, clinical type of otitis, cytological findings, maintenance protocol, concomitant allergy management when recorded, follow‐up information and number of relapses during the study period. Owner telephone follow‐up was performed to confirm whether the dog had continued maintenance treatment and to update relapse information. When no response was obtained, the dog was excluded from the final analysis. Therefore, all 71 dogs included in the final cohort had confirmed treatment continuation, updated relapse information and complete 12‐month follow‐up.
2.4. Treatment Protocols
All included dogs received proactive hydrocortisone aceponate maintenance therapy. Dogs were classified into two groups according to the prescribed schedule. Protocol 1 consisted of application on two consecutive days. Protocol 2 consisted of application on two non‐consecutive days per week, separated by at least two treatment‐free days. Treatment allocation was not randomised and reflected the attending clinician's judgement and routine practice.
During maintenance, clinically stable dogs received a chlorhexidine‐based ear cleaner once weekly, 24 h before hydrocortisone aceponate application. This ear‐cleaning schedule was used once weekly irrespective of whether hydrocortisone aceponate was applied on two consecutive or two non‐consecutive days.
Treatment used to achieve remission before entry into the maintenance period, and rescue treatment used in case of relapse, were selected according to otoscopic findings and otic cytology. Malassezia overgrowth was treated with a topical combination of miconazole nitrate, polymyxin B sulphate and prednisolone acetate, eight drops twice daily for 14 days, combined with a chlorhexidine‐based ear cleaner once daily for 14 days. Coccoid bacterial infection, defined cytologically by cocci associated with neutrophilic inflammation and/or intracellular bacteria, was treated with a topical combination of hydrocortisone aceponate, miconazole nitrate and gentamicin sulphate, one pump once daily for 14 days, combined with a chlorhexidine/Tris‐EDTA ear solution once daily for 14 days. Rod‐shaped bacterial infection and mixed infection (rods and cocci) were treated with a topical combination of marbofloxacin, clotrimazole and dexamethasone acetate, eight drops once daily for 14 days, combined with a chlorhexidine/Tris‐EDTA ear solution once daily for 14 days. When Pseudomonas spp. infection was diagnosed, an N‐acetylcysteine/Tris‐EDTA solution, 2 mL once daily, was applied 30 min before a topical enrofloxacin/dexamethasone/sodium chloride solution once daily; these cases also received oral prednisolone at 1 mg/kg once daily for 14 days. Dogs requiring a different rescue regimen or a change in maintenance or allergy management were not retained in the final analysis.
2.5. Outcome Measures
The primary outcome was the occurrence of at least one relapse during maintenance therapy within the 12‐month observation period. Relapse was defined as a recurrent episode of otitis externa requiring veterinary examination, cytological confirmation and additional otic treatment. Secondary outcomes were occurrence of multiple relapses, defined as two or more relapses, and total relapse count during the observation period. Because all dogs were observed for exactly 12 months, the total relapse count per dog was equivalent to the relapse rate per dog‐year.
2.6. Statistical Analysis
Descriptive statistics were used to summarise population characteristics and treatment outcomes. Continuous variables were reported as median and range. Categorical variables were reported as number and percentage. Signalment and baseline otitis characteristics were compared between treatment protocols. Continuous variables were compared with Mann–Whitney U tests. Categorical variables were compared using Fisher exact tests for 2 × 2 tables or chi‐square tests for larger contingency tables. The proportions of dogs with at least one relapse and with multiple relapses were compared between protocols using Fisher exact tests. Relapse counts were compared using a Mann–Whitney U test. Relative risks and 95% confidence intervals were calculated for Protocol 2 compared with Protocol 1. Statistical significance was set at p < 0.05. Because the comparison between protocols was secondary and exploratory, results were interpreted with emphasis on effect size, confidence intervals and clinical plausibility rather than on p values alone. No non‐inferiority or equivalence margin was prespecified, and the study was not designed or powered as a non‐inferiority or equivalence trial.
3. Results
3.1. Study Population
Medical records of 104 dogs prescribed hydrocortisone aceponate ear spray for proactive management of allergic otitis externa were screened. Seventy‐one dogs met the final inclusion criteria. Thirty‐three dogs were excluded because treatment was not started or not continued for the required period, the maintenance schedule or concomitant allergy management changed, owner follow‐up could not confirm the required information, or complete 12‐month outcome data were not available. All dogs received hydrocortisone aceponate ear spray. All included dogs had 12 months of follow‐up, and continuation of the prescribed maintenance protocol was confirmed by owner telephone follow‐up. Thirty‐six dogs received Protocol 1 and 35 dogs received Protocol 2. Study population and treatment protocol distribution are summarised in Table 1 . Age differed between groups: dogs receiving Protocol 1 had a median age of 5 years (range, 1–14), whereas dogs receiving Protocol 2 had a median age of 7 years (range, 1–15; p = 0.041). Body weight and sex distribution did not differ significantly between groups ( p = 0.324 and p = 0.196, respectively; Table 1 ). Forty‐six breeds were represented. The most frequent breeds were French Bulldog (8/71), English/American Cocker Spaniel (8/71), Labrador Retriever (6/71), Golden Retriever (3/71) and Maltese (3/71).
Study population and comparison of signalment data between treatment protocols.
Note : Data are presented as n (%) unless otherwise stated. p values are from Mann–Whitney U tests for continuous variables and chi‐square testing for sex distribution.
3.2. Baseline Otitis Characteristics
Before maintenance therapy, otitis externa was bilateral in 55/71 dogs (77.5%) and unilateral in 16/71 dogs (22.5%). The most common baseline clinical type was ceruminous otitis, followed by erythematous, purulent and ulcerative otitis. Baseline cytology most commonly identified Malassezia spp.; no organisms were recorded in 17/71 dogs (23.9%). Baseline otitis characteristics are summarised in Table 2 . Baseline laterality, clinical type, cytological category and amount score did not differ significantly between protocols (Table 2 ).
Baseline otitis characteristics before induction of remission and therapy and comparison between protocols.
Note : For dogs with different clinical type or cytological findings between ears, the more severe clinical type was used for classification where applicable. p values are from Fisher exact testing for laterality, chi‐square testing for clinical type and cytological category, and Mann–Whitney U testing for amount score.
3.3. Overall Relapse Outcome
Over the 12‐month observation period, 50/71 dogs (70.4%; 95% CI, 58.4–80.7%) had no relapse and 21/71 dogs (29.6%; 95% CI, 19.3–41.6%) had at least one relapse. Twelve dogs (16.9%; 95% CI, 9.0–27.7%) had one relapse, whereas nine dogs (12.7%; 95% CI, 6.0–22.7%) had multiple relapses. Overall relapse outcomes and comparisons between protocols are summarised in Table 3 . The total relapse count was 39 over 71 dog‐years, corresponding to 0.55 relapses/dog‐year.
Relapse outcomes overall and according to maintenance protocol during the fixed 12‐month observation period.
Note : Protocol 1 = application on two consecutive days; Protocol 2 = application on non‐consecutive days. RR = relative risk for Protocol 2 compared with Protocol 1; CI = confidence interval. Because all dogs were observed for 12 months, relapse count per dog is equivalent to relapses per dog‐year. Fisher exact tests were used for categorical outcomes and the Mann–Whitney U test for relapse counts.
3.4. Comparison Between Maintenance Protocols
At least one relapse occurred in 9/36 dogs (25.0%; 95% CI, 12.1–42.2%) receiving Protocol 1 and in 12/35 dogs (34.3%; 95% CI, 19.1–52.2%) receiving Protocol 2. This difference was not statistically significant (relative risk for Protocol 2 compared with Protocol 1, 1.37; 95% CI, 0.66–2.84; p = 0.443). Multiple relapses occurred in 2/36 dogs (5.6%; 95% CI, 0.7–18.7%) receiving Protocol 1 and 7/35 dogs (20.0%; 95% CI, 8.4–36.9%) receiving Protocol 2. This numerical difference did not reach statistical significance (relative risk, 3.60; 95% CI, 0.80–16.15; p = 0.085). Total relapse count was 14 in Protocol 1 and 25 in Protocol 2. Because each dog contributed one year of observation, relapse rates were 0.39 relapses/dog‐year for Protocol 1 and 0.71 relapses/dog‐year for Protocol 2. Median relapse count was 0 in both groups, and relapse counts did not differ significantly between protocols ( p = 0.290; Table 3 ).
4. Discussion
The present study describes relapse frequency during a 12‐month observation period in dogs with allergic otitis externa that entered proactive hydrocortisone aceponate maintenance therapy after clinical and cytological remission. In this verified cohort, 70.4% of dogs had no relapse and a further 16.9% had only one relapse. These findings are broadly consistent with the recent retrospective study by Lorente‐Méndez and Alonso‐Miguel, in which hydrocortisone aceponate was used for the reactive and proactive management of non‐infectious chronic or recurrent otitis externa, and 79.1% of treated ears remained recurrence‐free over a mean follow‐up of 202.6 days (Lorente‐Mendez and Alonso‐Miguel 2025 ). Direct comparison is limited because that study analysed ears rather than dogs, included chronic or recurrent non‐infectious otitis externa rather than allergic otitis externa specifically, used severity‐adapted treatment schedules, and had a variable follow‐up period. By contrast, the present study used the dog as the unit of analysis, required clinical and cytological remission before maintenance therapy, and assessed relapse over a fixed 12‐month observation period. Nevertheless, both studies support the use of sustained topical anti‐inflammatory maintenance therapy for the prevention of relapses of recurrent allergic otitis externa.
Dogs treated on two consecutive days had numerically fewer relapses, particularly multiple relapses, than dogs treated on non‐consecutive days. However, this finding must be interpreted with caution, as no statistically significant difference was detected between the two maintenance schedules. The study was not designed or powered as a non‐inferiority or equivalence trial, and the small number of dogs and relapse events limits the ability to detect a true difference between schedules. The lower relapse frequency observed in the consecutive‐day group should be considered hypothesis‐generating and requires evaluation in a prospective controlled study with adequate sample size.
The comparison between schedules was also limited by the observational nature of the study. Treatment allocation was not randomised and reflected routine clinical practice. Although baseline characteristics were compared between groups, unmeasured differences in previous relapse pattern, ear canal changes, owner adherence or clinician preference may have influenced the choice of maintenance schedule. In addition, dogs in Protocol 2 were older than dogs in Protocol 1, and age cannot be excluded as a potential confounding factor. Therefore, the protocol comparison should be interpreted as exploratory rather than confirmatory.
The results should not be interpreted as evidence that maintenance therapy alone controls all aspects of allergic otitis externa. Proactive topical treatment targets the inflammatory component of the ear canal, but allergic disease remains multifactorial. Allergen avoidance where possible, control of ectoparasites, management of food allergy when present, appropriate treatment of secondary infection, ear cleaning when indicated and systemic anti‐inflammatory or antipruritic therapy may all influence outcome. Previous work in canine atopic dermatitis has shown that hydrocortisone aceponate can reduce skin lesions and pruritus (Nam et al. 2012 ; Nuttall et al. 2009 ; Nuttall et al. 2012 ), and combination with systemic treatment may help prevent deterioration when systemic therapy is tapered (Takahashi et al. 2021 ).
The broader proactive‐treatment concept is also supported by Lourenço et al. ( 2016 ), in which intermittent hydrocortisone aceponate spray prolonged time to relapse in canine atopic dermatitis, although that study was prospective, placebo‐controlled and focused on cutaneous lesions rather than otitis externa.
In the present study, dogs were retained in the final analysis only if concomitant allergy management remained stable during the 12‐month observation period. This included systemic antipruritic or anti‐inflammatory treatment, allergen‐specific immunotherapy and diet, when applicable. This criterion was intended to reduce the effect of major therapeutic changes on otitis relapse frequency. Nevertheless, concurrent allergy treatments were not randomised or standardised, and their possible influence on relapse risk cannot be excluded.
By including only dogs with confirmed continuation of the prescribed maintenance protocol, stable concomitant allergy management and complete 12‐month outcome information, the present analysis gives a clearer estimate of relapse frequency among dogs that actually received the intended maintenance regimen. However, this choice also introduces selection bias. Dogs that stopped treatment, used the product incorrectly, changed allergy treatment, lacked complete records or could not be contacted were excluded. Dogs that discontinued treatment because of perceived lack of efficacy, or because they were stable and owners elected to stop treatment, were therefore not represented in the final cohort. The results should consequently be interpreted as outcomes in a verified adherent cohort, not as an intention‐to‐treat estimate of all dogs initially prescribed hydrocortisone aceponate maintenance therapy.
Relapse was defined more strictly than owner‐reported recurrence alone, requiring veterinary examination, otic cytology and additional otic treatment. However, retrospective relapse assessment remains vulnerable to recall and recording bias. Minor episodes managed by owners without veterinary examination, or episodes treated elsewhere without complete documentation, may have been missed. Exact dates of relapse were not consistently available, so time‐to‐first‐relapse analysis could not be performed. This limitation is partly mitigated by the fixed 12‐month observation period, which allowed relapse frequency and relapse rate per dog‐year to be compared between groups, but it prevents comparison of relapse timing. Adherence was confirmed by owner report but was not objectively measured. Finally, the study had no untreated control group; therefore, it cannot prove that hydrocortisone aceponate maintenance therapy caused the low relapse frequency, only that relapse frequency was low in dogs that continued the intended regimen under stable management conditions.
5. Conclusion
In this retrospective field cohort of dogs with allergic otitis externa that entered proactive hydrocortisone aceponate maintenance therapy after clinical and cytological remission, most dogs had no relapse or only one relapse during a fixed 12‐month observation period. No statistically significant difference was detected between consecutive‐day and non‐consecutive‐day maintenance protocols; however, the study was not designed or powered to demonstrate equivalence or non‐inferiority between schedules. These findings support further prospective evaluation of proactive topical anti‐inflammatory maintenance therapy as part of long‐term management of allergic otitis externa, including adequately powered comparison of maintenance schedules and standardised assessment of relapse timing.
Author Contributions
Elisa Maina : Conceptualisation; methodology; investigation; formal analysis; supervision; project administration; writing – original draft; writing – review and editing. Rigert Jasmine Chantale : Investigation; data curation; writing – review and editing. Carlotta Filippini : Investigation; data curation; writing – review and editing. Regula Cao : Investigation; data curation; validation; writing – review and editing. Ana Oliveira : Validation; writing – review and editing.
Funding
The authors have nothing to report.
Ethics Statement
The authors confirm that the ethical policies of Veterinary Medicine and Science have been adhered to. This was a retrospective review of clinical records from client‐owned dogs treated as part of routine veterinary care with a commercially licensed veterinary medicinal product authorised for otic use. No procedures were performed for research purposes and formal ethical approval was not required under the applicable institutional and national regulations.
Patient/Client Consent Statement
Informed client consent was obtained for diagnostic and therapeutic procedures performed as part of routine veterinary care. Owner telephone follow‐up was performed to confirm treatment continuation and clinical outcome. Data were anonymised before analysis.
Conflicts of Interest
The authors declare no conflicts of interest.
Data Availability Statement
The data that support the findings of this study are not publicly available because they contain confidential clinical information from client‐owned animals. Anonymised data may be made available from the corresponding author upon reasonable request and subject to applicable institutional and data‐protection requirements.