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Proliferative and necrotising otitis externa in a cat without pinnal involvement: video-otoscopic features 无耳廓病变的猫增生性和坏死性外耳炎:视频耳镜下的特征 翻译：郭润霞
Abstract Proliferative and necrotising otitis externa is a rare and recently described disease affecting the ear canals and concave pinnae of kittens. This article describes a case of proliferative and necrotising otits externa in a young adult cat. In this case, the lesions did not affected the pinnae, but both ear canals were severely involved. Video-otoscopy revealed a digitally proliferative lesion, growing at 360°all around the ear canals for their entire length, without involvement of the middle ear. Histopathological examination confirmed the diagnosis, and the cat responded completely to a once-daily application of 0.1% tacrolimus ointment diluted in mineral oil in the ear canals. Video-otoscopy findings, not described previously, were very peculiar and may help clinicians to diagnose this rare disease. 摘要 增生性和坏死性外耳炎是一种罕见的、近期才有描述的影响幼猫耳道和耳廓凹面的疾病。本文描述了一例增生性和坏死性外耳炎的幼猫。本例病变未波及耳廓，但双耳道病变严重。视频耳镜检查发现明显增生性病变，沿耳道周围360°生长，未累及中耳。组织病理学检查确诊，猫对每日一次在耳道涂抹用矿物油稀释的0.1%他克莫司软膏反应良好。对于此前未曾报道过的此种情况，视频耳镜的发现可能有助于临床医生诊断这种罕见疾病。
Proliferative and necrotising otitis externa is a rare and recently described disease affecting the ear canals and concave pinnae of cats.So far, only five cases have been reported.The aetiology is currently unknown, although an immunological basis is suspected.In a recent case report, immunohistochemistry was used to show a closed association between caspase-3 stained keratinocytes and CD3+ T cells, consistent with keratinocyte apoptosis caused by epidermal-infiltrating T cells.So far, evidence of a viral aetiology has not been found: polymerase chain reaction for feline herpesvirus 1 and immunohistochemistry for papillomavirus have both been negative.Typically seen in kittens, this disease must be considered among the differential diagnoses (ectoparasitic, allergic, immune-mediated and neoplastic diseases) of bilateral otitis externa in young cats. 增生性和坏死性外耳炎是一种罕见的、近期描述的，影响猫耳道和耳廓凹面的疾病。迄今仅有5例报道。虽然目前病因尚不清楚，但怀疑存在免疫学基础。在最近的一份病例报告中，免疫组织化学被用来显示caspase-3染色的角质形成细胞和CD3 + T细胞之间的紧密关联，与表皮浸润T细胞引起的角质形成细胞凋亡一致。到目前为止，尚未发现病毒病因学的证据：猫疱疹病毒1的聚合酶链反应和乳头瘤病毒的免疫组化均为阴性。通常见于幼猫，在幼猫双侧外耳炎的鉴别诊断（外寄生性、过敏性疾病、免疫介导性疾病和肿瘤性疾病）中必须考虑本病。
The aim of this article is to describe a case of proliferative and necrotising otitis externa in a young-adult cat, which resolved completely with topical tacrolimus therapy. Confirmative diagnosis in this case was obtained with histopathological examination; however, video-otoscopy findings, not described previously, were very peculiar and may help clinicians to include proliferative and necrotising otitis in the list of differential diagnoses of feline otitis externa. 本文的目的是描述一例幼猫的增生性和坏死性外耳炎病例，其通过外用他克莫司治疗，症状完全消退。该病例的确诊是通过组织病理学检查确定的；然而，之前未描述的视频喉镜检查结果非常特殊，可能有助于临床医生将增殖性和坏死性耳炎纳入猫外耳炎的鉴别诊断列表中。
A 2-year-old castrated male domestic shorthair cat was presented for evaluation of chronic otitis externa. The owners reported that the cat had been pruritic at both ears for 7 months since it was found at the presumed age of 1.5 years. Since adoption, the cat lived indoors with no other pets and was vaccinated regularly, dewormed and fed commercial dry food. 一只2岁已去势雄性家养短毛猫因慢性外耳炎就诊。犬主人报告猫在大约1.5岁时发现双耳瘙痒并持续7个月。自领养以来，该猫在室内生活，无其他宠物，定期接种疫苗，驱虫并饲喂市售干食品。
Over the previous months, the cat had been treated with numerous topical preparations for otic parasites, yeast and bacterial infections,including thiabendazole/dexamethasone/neomycin sulfate (Tresaderm; Merial) for 1 week, miconazole nitrate/prednisolone/polimixin B (Surolan; Janssen Animal Health) for 5 days, polimixin B/lidocain/neomycin (Anauran; Zambon Italia) and PCMX/EDTA (Epi-Otic; Virbac) for 1 week. At the same time the cat was also treated with systemic drugs, including a single application of selamectin spot-on (Stronghold;Pfizer Animal Health) and enrofloxacin (Baytril; Bayer Animal Health) and itraconazole (Itrafungol; Janssen Animal Health) for 3 weeks. No response was observed with any of these treatments. 在过去的几个月里，猫接受了许多外部制剂治疗耳寄生虫、酵母菌和细菌感染，包括噻苯达唑/地塞米松/硫酸新霉素治疗1周，硝酸咪康唑/泼尼松龙/多粘菌素B治疗5天，多粘菌素B/利多卡因/新霉素和PCMX/EDTA连用1周。同时，猫还接受了全身性药物治疗，包括使用一次赛拉菌素滴剂，使用恩诺沙星和伊曲康唑3周。这些治疗均未观察到缓解。
General physical examination was unremarkable. The inner surface of both pinnae showed a small amount of black and dry cerumen. Otoscopic examination showed abundant black and dry cerumen in both ear canals and the tympanic membranes (TM) could not be visualised. Initial differential diagnoses were otoacariasis, which may have not resolved with previous treatments, and chronic bacterial or yeast otitis externa secondary to otitis media or, less likely, to bilateral ear polyps. Microscopic examination of the ear cerumen was negative for otic parasites and cytological examination showed only keratinocytes. In order to completely rule out otoacariasis, given the dry appearance of the ear cerumen and because previous treatments had been administered for short courses, an otic preparation containing thiabendazole/dexamethasone/neomycin sulfate was dispensed to be applied twice daily into both ear canals for 3 weeks. 全身体格检查无异常。双耳廓内表面可见少量黑色干燥耵聍。耳镜检查显示双耳道有丰富的黑色干燥的耵聍，鼓膜(TM)无法显示。初步鉴别诊断为耳螨病，既往治疗可能仍未排除耳螨，和继发于中耳炎或不太可能继发于双侧耳息肉的慢性细菌性或酵母菌性外耳炎。耳耵聍镜检耳寄生虫阴性，细胞学检查仅见角质形成细胞。为了完全排除耳螨病，考虑到耳耵聍的外观干燥，并且由于之前的治疗是短期给药，因此使用了含有噻苯达唑/地塞米松/硫酸新霉素的耳药制剂，每日两次涂抹到双耳道，持续3周。
The cat was re-examined 4 months later, showing very similar clinical signs. Otoscopic examination revealed abundant wet and black exudate in both ear canals with a small amount of the same material visible on the inner aspect of both pinnae. The removal of the otic material from the vertical ear canal allowed the detection of underlying erythema and erosions; the TM could not be visualised on either side. Pruritus was still present. Differential diagnoses were chronic bacterial or yeast otitis externa secondarily to otitis media or, less likely, to bilateral ear polyps. A neoplastic process was unlikely owing to the age of the cat and the bilateral involvement of the ear canals. Bilateral cytological examination of the otic exudate revealed degenerated neutrophils and intra- and extracellular cocci, suggesting bacterial otitis externa. 4个月后对猫进行重新检查，显示非常相似的临床症状。耳镜检查：双耳道内有丰富的潮湿、黑色渗出物，双耳廓内侧可见少量相同物质。从垂直耳道中取出耳分泌物可检测到潜在的皮肤发红和糜烂：鼓膜在两侧均无法观察到。瘙痒仍然存在。鉴别诊断为继发于中耳炎的慢性细菌性或酵母菌性外耳炎，或不太可能继发于双侧耳息肉。由于猫的年龄和双侧耳道病变，肿瘤过程不太可能发生。双侧耳道渗出液细胞学检查：退行性中性粒细胞，胞内外球菌，提示细菌性外耳炎。
The cat was premedicated with 5 µg/kg medetomidine (Domitor; Pfizer Italia) and 10 mg/kg ketamine (Imalgene; Merial Italia) intramuscularly and induced with 4 mg/kg propofol (Rapinovet; Schering Plough) intravenously, followed by maintenance with isoflurane in oxygen. The cat was positioned in lateral recumbency and both external ear canals were examined with a 2.7 mm 30° videoscope (Karl Storz GmbH, Tuttlingen, Germany) after flushing with saline to remove the otic exudate. Both right and left external ear canals were characterised by a proliferative appearance of the wall, which partially obstructed the scope passage. A digitally proliferative lesion, growing at 360° all around the ear canals and for the entire length of the canals could be seen, while it was not possible to visualise the normal vascularisation (Figure 1). The ear canal walls were found to be bleeding easily andinflamed. The TM could be examined completely at the end of the left ear canal, while in the right ear canal a dark, brown-to-black, vegetative plaque covered most of the TM. The plaque was removed with the aid of endoscopic clamps and a ruptured TM was observed. The proliferative disease protruding in the middle ear without affecting the tympanic cavity was detected. The tympanic cavity appeared normally covered by a pinkish and well-vascularised respiratory mucosa (Figure 2). 猫预先肌肉注射5µg/kg美托咪定和10 mg/kg氯胺酮，并静脉注射4 mg/kg丙泊酚诱导，然后用异氟烷和氧气维持。猫取侧卧位，用生理盐水冲洗去除耳渗出液后，用2.7 mm 30°视频示波器检查双侧外耳道。左右外耳道均表现为耳道壁增生性外观，部分阻塞内镜通过。可见指（趾）状增生性病变，360°生长于耳道周围和整个耳道，而无法可视化正常血管形成（图1）。发现耳道壁易出血、发炎。左耳道末端可检查到鼓膜，而在右耳道内鼓膜被大部分暗的、棕黑色的斑块遮挡。在内镜钳的辅助下清除斑块，观察到鼓膜破裂。检测到突入中耳而不影响鼓室的增生性疾病。鼓室似乎被粉红色和血管化良好的粘膜正常覆盖（图2）。
The nasopharyngeal inspection did not reveal any anatomical or pathological modifications during the retroversion technique with a flexible 5 mm 0° videoscope (Olympus Italia). 在使用灵活的5 mm 0°视频镜向后弯曲进行检查时，鼻咽检查未发现任何解剖或病理改变。
Multiple biopsy samples were taken for histopathological examination with the aid of the endoscopic forceps. Biopsy samples were fixed in 10% buffered formalin, embedded in paraffin, sectioned at 5 µm and stained with haematoxylin and eosin. Histopathological examination showed markedly hyperplastic epidermis with moderate and focal spongiosis and lymphocytic exocytosis. Hyperplasia extended into the wall of follicular infundibula (Figure 3). There were a few dyskeratosic keratinocytes (Figure 4) and large and thick parakeratotic plaques with colonies of coccoid bacteria could be observed focally in one biopsy sample from the left external ear canal. The dermal inflammatory infiltrate was mixed with neutrophils, lymphocytes and other mononuclear cells. In one ear biopsy there were also a few eosinophils. Periodic-acid Schiff stain wasperformed to rule out Malassezia species overgrowth and dermatophytosis; the result was negative. Although keratinocyte dyskeratosis was very mild, the epidermal and follicular hyperplastic changes were striking and, together with the clinical lesions, were considered typical of proliferative and necrotising otitis externa. 在内镜钳的辅助下取多个活检标本进行组织病理学检查。将活检样本固定在10%福尔马林缓冲液中，包埋在石蜡中，以5µm切片，并用苏木精和伊红染色。组织病理学检查显示表皮明显增生伴中度和局灶性海绵形成和淋巴细胞胞吐作用。增生扩展至毛囊漏斗壁（图3）。左外耳道活检标本中可局灶性观察到少量角化不良角质形成细胞（图4）和大而厚的角化不全斑块伴球状细菌菌落。真皮炎性浸润与中性粒细胞、淋巴细胞和其他单核细胞混合。在一侧耳道活检中，也有一些嗜酸性粒细胞。进行过碘酸雪夫染色以排除马拉色菌属过度生长和皮肤癣菌病；结果为阴性。尽管角质形成细胞角化不良非常轻微，但表皮和毛囊增生性变化显著，结合临床病变，认为是典型的增生性和坏死性外耳炎。
Therapy was initiated with 10 g 0.1% tacrolimus ointment (Protopic; Astellas Pharma) diluted in 10 ml mineral oil to be applied into both ears once daily for 6 weeks. Clotrimazole/dexametasone/marbofloxacin eardrops (Aurizon; ATI Pets) were also prescribed to be applied once daily for 3 weeks to treat the bacterial otitis externa. 治疗开始时，将10 g 0.1%他克莫司软膏稀释于10 mL矿物油中，涂抹于双耳，每日一次，持续6周。还使用了克霉唑/地塞米松/马波沙星滴耳液，每日一次，持续3周，用于治疗细菌性外耳炎。
The cat was re-examined 6 weeks later, and both pinnae and ear canals appeared normal on otoscopic examination. A small amount of cerumen still obscured the TM on the left side, while the TM on the right side could be visualised normally. Cytological examination of the ear cerumen showed keratinocytes only. 该猫6周后复查，耳廓及耳道均表现正常。左侧鼓膜仍有少量耵聍遮挡，而右侧鼓膜可正常显影。耳道耵聍细胞学检查仅见角质形成细胞。
Proliferative and necrotising otitis externa was reported initially as a disease that typically affected kittens; however, two of the five cases reported previously occurred in a 3-year-old and a 4-year-old cat, respectively.In this case, the age of onset is not defined clearly, as the affected cat was adopted at approximately 1 year of age and already showed bilateral ear pruritus. 增生性和坏死性外耳炎最初被报道为一种通常影响幼猫的疾病；然而，之前报告的5例病例中的2例分别发生在3岁和4岁的猫中。本病例，发病年龄定义不明确，因为患病猫在约1岁时被收养，并已表现出双耳瘙痒。
The clinical presentation of this case is somewhat different to the ones reported in previous publications.Feline proliferative and necrotising otitis externa usually involves both the pinnae and ear canals, with dark-coloured coalescing plaques covering the concave surface of the pinnae and external ear canals. Otoscopic examination is not always possible owing to the large amount of material that accumulates in the ear canals. Pruritus may be present or not and a secondary bacterial or yeast otitis externa is invariably present. In this case, the concave aspects of the pinnae were not affected, with lesions similar to the ones reported affecting only the external ear canals. The cat was extremely pruritic and the primary disease was complicated by secondary bacterial otitis externa. 该病例的临床表现与既往报道中的临床表现略有不同。猫增生性和坏死性外耳炎通常同时累及耳廓和耳道，耳廓和外耳道凹面覆盖深色斑块状结痂。由于大量物质在耳道内蓄积，耳镜检查并不总是可行的。可能存在或不存在瘙痒，总是存在继发性细菌性或酵母菌性外耳炎。本病例中，耳廓的凹面不受影响，病变与报告的仅影响外耳道的病变相似。猫极度瘙痒，原发病导致继发细菌性外耳炎。
Otoscopic evaluation of the external ear canal and TM should always be performed in animals presenting with otitis externa.The enhanced illumination and magnification of video-otoscopy provide the practitioner with more detailed information for diagnosis and prognosis. The configuration of the working channel facilitates sampling, improves efficacy of cleaning procedures, and decreases the risk of iatrogenic injuries to structures of the middle and inner ear. Direct examination of the ear canals revealed a specific pathological finding. The video-otoscopy findings observed in this cat were peculiar, with unusual, digitally-protruding lesions extending for the entire length of the canal and growing at 360° round the ear canal. Necrotising proliferative otitis externa is usually characterised by ulcerated, proliferative or sclerotic lesions.Surprisingly, the right tympanic membrane was broken, with no middle ear involvement. Even if the procedure was performed under direct visualisation, the possibility of an iatrogenic lesion during plaque removal with the endoscopic clamps cannot be excluded. 对于出现外耳炎的动物，应始终进行外耳道和鼓膜的耳镜评价。视频透视的增强照明和放大作用为执业医师提供了更详细的诊断和预后信息。工作通道的配置便于采样，提高了清洁程序的有效性，并降低了中耳和内耳结构医源性损伤的风险。直接检查耳道发现特异性病理结果。在这只猫中观察到的视频耳镜发现是特殊的，不寻常的、明显突出的病变延伸到整个耳道长度，并在耳道周围360°生长。坏死性增生性外耳炎通常表现为溃疡、增生或硬化病变。令人惊讶的是，右侧鼓膜破裂，无中耳患病。即使手术是在直接可视化下进行的，也不能排除使用内镜钳去除结痂过程中造成医源性损伤的可能。
The main histopatological alterations observed in the skin biopsies were the hyperplastic changes in the epidermis, as well as in the follicular walls. This lesion accounts for one of the terms used to describe the disease, namely proliferative otitis.Necrotic changes, which account for the second term used to name the disease, were less prominent and dyskeratosis was only occasionally seen; nevertheless, other diseases were considered unlikely.The main histopathological differential diagnosis would have been an adverse reaction to topical medications; however, in this condition apoptosis with satellitosis and less hyperplastic changes would have been expected.Moreover, the application of topical ointments did not lead to worsening of the condition. 在皮肤活检中观察到的主要组织病理学变化为表皮以及毛囊壁的增生性变化。这种病变符合描述该病的术语之一，即增生性耳炎。用于命名疾病的第二个术语的坏死性变化不太明显，仅偶尔观察到角化不良；然而，认为不太可能是其他疾病。主要的组织病理学鉴别诊断是外用药物的不良反应；然而，在这种情况下，预期应为细胞凋亡伴卫星样变和较少的增生性变化。而且，外用软膏的应用不会导致病情恶化。
Tacrolimus is reported to be an effective therapy for this disease.However, tacrolimus is marketed as an ointment, which may be difficult to apply deeply into the ear canals owing to its thickness. For this reason, it was decided to reformulate 0.1% tacrolimus ointment, diluting 10 g in 10 ml mineral oil. This made the ointment far more liquid and allowed the active ingredient to penetrate more deeply in the ear canals. Although the patient was a very cooperative cat, once daily application was preferred in order to overcome problems related to burning or itching sensations reported as adverse effects of topical application of tacrolimus. The concurrent once daily application of a topical preparation for otitis externa (Aurizon; ATI Pets) effectively resolved the secondary bacterial otitis externa. According to previous case reports it is not clear whether dexamethasone acetate, contained in this topical preparation, might have a synergistic effect with tacrolimus in the treatment of proliferative and necrotising otitis externa. 据报道，他克莫司是治疗本病的有效疗法。然而，他克莫司作为软膏上市，由于其粘稠，可能难以深入耳道。为此，决定重新配制0.1%他克莫司软膏，用10 mL矿物油稀释10g软膏。这使得软膏的液态性更强，使活性成分更深入地渗入耳道。尽管患病动物是一只非常配合的猫，但为了不造城他克莫司外部给药不良反应与烧灼感或瘙痒感相关的问题，首选每日一次给药。同时每日一次应用外耳炎局部制剂可有效消退继发性细菌性外耳炎。根据之前的病例报告，尚不清楚该外用制剂中所含的醋酸地塞米松是否可能与他克莫司在治疗增生性和坏死性外耳道炎方面具有协同效应。
file:///C:/Users/asus/AppData/Local/Temp/ksohtml14320/wps1.jpg Figure 1 Video-otoscopy of the external ear canal. A digitally proliferative disease extends the entire canal length 图1视频耳镜下的外耳道。明显增生性疾病延伸整个耳道
file:///C:/Users/asus/AppData/Local/Temp/ksohtml14320/wps2.jpg Figure 2 Video-otoscopy of the middle ear. The proliferative disease protrudes into the middle ear without affecting the normal respiratory mucosa 图2视频耳镜下的中耳。增生性疾病突向中耳，不影响正常耳道黏膜
file:///C:/Users/asus/AppData/Local/Temp/ksohtml14320/wps3.jpg Figure 3 Histopathology of the ear canal. Marked hyperplasia of the follicular wall (*) accompanied by epidermal parakeratosis and erosion (haematoxylin and eosin, bar = 300 µm) 图3耳道组织病理。毛囊壁明显增生(*)伴表皮角化不全和糜烂（苏木精和伊红，标尺 = 300µm）
file:///C:/Users/asus/AppData/Local/Temp/ksohtml14320/wps4.jpg Figure 4 Histopathology of the ear canal. Dyskeratotic keratinocyte in the hyperplastic follicular wall (arrow) (haematoxylin and eosin, bar = 100 µm) 图4耳道组织病理学。增生的毛囊壁角化不良角质形成细胞（箭头）（苏木精和伊红，标尺= 100µm）
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发表于 2022-6-27 21:05:00
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