犬双侧脓性肉芽肿性外耳炎伴推测的软骨破坏:一例严重耳廓软骨炎 ...

王帆

Bilateral pyogranulomatous otitis externa with putative cartilage destruction in a dog: A severe case of auricular chondritis?

犬双侧脓性肉芽肿性外耳炎伴推测的软骨破坏:一例严重耳廓软骨炎病例?

 

作者：Michela De Lucia | Carolina Mendes | Giovanna Bertolini

 

翻译：王帆

 

Abstract

摘要

Auricular chondritis of unknown cause was suspected in a 10-year-old male Bolognese dog with a five-month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals.

一只10岁的博洛尼亚雄性犬被怀疑有不明原因的耳软骨炎，它有5个月的双侧耳廓疼痛的结节性和溃疡性化脓性肉芽肿性皮肤病病史，推测有耳软骨破坏。使用免疫抑制剂量的泼尼松龙后，疼痛和病变消退，但这种疾病导致耳廓和外耳道发生畸形。

 

KEYWORDS

关键词

auricular chondritis, dog

耳软骨炎;犬

 

 

 

INTRODUCTION

介绍

The term ‘auricular chondritis’ refers to an immunemediated inflammatory process of the auricular cartilage described in humans and other animal species, including cats and, more rarely, dogs. According to the limited literature available, the disease manifests in dogs as a painful nodular swelling of one or both pinnae and is characterised histologically by necrosis of the auricular cartilage surrounded by lymphoplasmacytic and pyogranulomatous inflammation. Cartilage destruction causing ear deformity is a well-known complication of auricular chondritis in humans, yet it has never been described in dogs. This report describes a case of bilateral pyogranulomatous otitis externa (OE) with putative cartilage destruction in a dog, suspected to be a severe advanced form of auricular chondritis.

“耳软骨炎”一词是指耳廓软骨的免疫介导的炎症过程，见于人类和其他动物物种，包括猫和更罕见于犬。根据现有的有限文献，该病在犬的表现为一个或两个耳廓的疼痛结节性肿胀，组织学特征为耳廓软骨的坏死，周围是淋巴浆细胞性和化脓性肉芽肿性炎症。软骨破坏导致耳畸形是人类耳廓软骨炎的一个众所周知的并发症，但从未在犬中描述过。本报告描述了一个双侧化脓性肉芽肿性外耳炎(OE)的病例，推测软骨破坏的犬，怀疑是一种严重的晚期形式的耳软骨炎。

 

CASE REPORT

病例报告

A 10-year-old neutered male Bolognese dog was referred to the Dermatology Service for chronic, painful/nonpruritic bilateral otitis. Five months earlier, the dog had experienced sudden pain in the ear and neck regions without any visible lesions, followed a few days later by fever, poor appetite, and bilateral swelling and ulceration of the pinnae. Chronic OE was diagnosed, and several systemic and topical treatments were administered without any improvement. Treatments included amoxicillin and clavulanic acid, nonsteroidal anti-inflammatory drugs, oclacitinib, anti-inflammatory doses of prednisolone and multiple ear medications. A more detailed medical history could not be reconstructed.

一只10岁的已去势雄性博洛尼亚犬因慢性、疼痛/无瘙痒的双侧耳炎被转诊到皮肤科就诊。5个月前，这只犬突然感到耳朵和颈部疼痛，但没有任何可见的病变，几天后出现发热、食欲不振、双侧耳廓肿胀和溃疡。诊断为慢性OE，给予多种全身和外用药治疗，但无任何改善。治疗包括阿莫西林克拉维酸、非甾体抗炎药、奥拉替尼、抗炎剂量的泼尼松龙和多种耳部药物。无法重建更详细的病史。

 

At the time of presentation, severe pain prevented any examination of the ears in the awake patient. The rest of the dermatological and general physical examination was unremarkable. Complete blood count and serum biochemical analysis revealed thrombocytosis (603×103 platelets/μL) and an increased alkaline phosphatase level (487IU/L), possibly related to the previous glucocorticoid treatments. General anaesthesia was performed to allow a thorough examination of both ears. Lesions consisted of diffuse, severe, erythematous and multinodular swelling associated with multifocal ulcers on the concave aspect of the pinnae extending to the entrance of the ear canals. Severe stenosis of both external ear canals prevented otoscopic examination (Figure 1). Cytological examination of ear canal exudate revealed red blood cells, neutrophils, and occasional Malassezia yeasts and bacterial cocci. Based on the history and the unique appearance of the lesions, auricular chondritis was suspected and computed tomography (CT) and pinnal biopsies were performed under general anaesthesia.

就诊时，患犬清醒情况下因剧烈疼痛无法进行任何耳部检查。其余皮肤科和一般体格检查未见异常。血常规和生化检查提示血小板增多(603×103血小板/μL)和碱性磷酸酶升高(487IU/L)，可能与既往糖皮质激素治疗有关。进行全身麻醉，以便对双耳进行彻底检查。病变包括弥漫性、严重的发红和多结节性肿胀，伴多灶性溃疡，位于耳廓凹侧，延伸至耳道入口。双侧外耳道重度狭窄妨碍了耳镜检查(图1)。耳道分泌物的细胞学检查显示红细胞、中性粒细胞，偶见马拉色菌和细菌球菌。结合病史及特殊的病变表现，考虑耳软骨炎可能，全麻下行CT检查及耳廓活检。

 

The CT images showed diffuse soft tissue thickening in the cartilaginous portion of the auricular pinna with nodular aspects and areas of increased tissue density. Both external auditory canals appeared stenotic and contained some fluid. Middle retropharyngeal and superficial cervical lymph nodes were moderately enlarged bilaterally. The middle and inner ear structures were interpreted to be normal bilaterally, as were all other structures of the splancno- and neurocranium (Figure 2).

CT表现为耳廓软骨区域弥散性软组织增厚，呈结节状，组织密度增高。双侧外耳道均出现狭窄，并含有少量液体。双侧咽后中部和颈部浅表淋巴结中度肿大。中耳和内耳结构判读为双侧正常，脊髓和颅脑的所有其他结构也是正常的(图2)。

 

Three 8-mm punch biopsies were taken from the concave surface of the scapha, two from the right and one from the left ear. Considerable softness of the tissue was noted during the biopsy punch insertion, suggesting that the cartilage tissue was abnormal or absent. On the left pinna, where lesions appeared to be more severe, an additional biopsy was performed using the double-trephine punch biopsy technique to assure that the cartilage was sampled.Once the 8-mm punch sample was removed, a 4-mm punch was used within the centre of the 8-mm defect to obtain the deeper tissue. Histopathological findings consisted of nodular-to-diffuse, superficial-to-deep, pyogranulomatous dermatitis with multifocal dermal necrosis and extensive epidermic ulceration (Figure 3a,b). Despite multiple cuts, cartilage was not identified in any of the biopsy samples and appeared to be replaced by fibrosis and multinucleated myocytes (Figure 3c). Special stains including periodic acid Schiff, Brown–Brenn and Fite–Faraco, and immunohistochemical investigation to detect Leishmania amastigotes were all negative.

在耳舟的凹面进行了3个8毫米的打孔活检，2个来自右耳，1个来自左耳。打孔过程中观察到组织相当柔软，提示软骨组织异常或缺失。在左侧耳廓，病变似乎更严重，使用双环钻活检技术进行了额外的活检，以确保评估软骨样本。一旦8毫米的冲孔样本被移除，在8毫米缺损的中心使用一个4毫米的冲孔来获得更深的组织。组织病理学检查结果包括结节至弥漫性、浅表至深部、化脓性肉芽肿性皮炎伴多灶性真皮坏死和广泛表皮溃疡(图3a,b)。尽管有多处切割，但在任何活检样本中均未发现软骨，并且似乎被纤维化和多核肌细胞取代(图3c)。过碘酸希夫染色、Brown-Brenn染色、Fite-Faraco染色及利什曼原虫无鞭毛体免疫组化检查均为阴性。

 

A sterile pyogranulomatous process was hypothesised, and oral ciclosporin (Cyclavance; Virbac) at a dose of 5mg/kg per os (p.o.) twice daily, was started. Meloxicam (Metacam; Boehringer Ingelheim) also was prescribed for the first fivedays of treatment at a dose of 0.1mg/kg p.o. once daily for pain management. Topical treatments were not feasible because manipulation of the ears was too painful. Four weeks later, only slight improvement was observed, so ciclosporin was withdrawn and prednisolone (Prednicortone; Dechra) was started at a dose of 2mg/kg p.o. once daily. Three weeks later, a dramatic reduction in lesions and pain was observed, and prednisolone was tapered by 25% to minimise adverse effects. Pain and pinnal swelling and ulcers completely resolved within twomonths after starting the prednisolone therapy. At that point, the pinnae appeared shrunken and floppy, and otoscopic examination was still not possible as the opening of both ear canals was reduced to a pinpoint. Moreover, it was not possible to palpate any cartilaginous tissue of the pinna or the ear canal (Figure 4). During the subsequent fivemonths, prednisolone was slowly tapered until it was discontinued. No relapses had been observed threemonths after prednisolone withdrawal.

假设为无菌性化脓性肉芽肿过程，并口服环孢素的剂量为5mg/kg/os (p.o)，每日2次。治疗的前5天也使用了美洛昔康，每日1次，每次0.1mg/kg的剂量用于疼痛管理。外部治疗不可操作，因为耳部操作太痛。4周后，仅观察到轻微改善，因此停用环孢素，并开始使用泼尼松龙的起始剂量为每日1次，每次2mg/kg。3周后，观察到病变和疼痛显著减轻，将泼尼松龙减量25%以尽量减少不良反应。疼痛、耳廓肿胀和溃疡在开始泼尼松龙治疗后2个月内完全缓解。这时，耳廓皱缩松软，耳镜检查仍然不可操作，因为双耳道的开口缩小到一个针尖。此外，无法触诊耳廓或耳道的任何软骨组织(图4)。在随后的5个月期间，泼尼松龙逐渐减量，直至停用。停用泼尼松龙3个月后未见复发。

 

DISCUSSION

讨论

To the best of the authors' knowledge, this is the first report of bilateral auricular cartilage destruction and external ear deformity associated with a severe pyogranulomatous otitis in a dog. An advanced and severe case of auricular chondritis was suspected. Unfortunately, despite multiple and deep biopsies of the pinnae, chondritis could not be demonstrated, as a result of the lack of cartilaginous tissue in the samples.

据作者所知，这是第一次报道双侧耳廓软骨破坏和外耳畸形伴发严重的化脓性肉芽肿性耳炎。疑似晚期和严重的耳廓软骨炎病例。不幸的是，尽管对耳廓进行了多次深部活检，但由于样本中缺乏软骨组织，无法证明软骨炎。

 

In humans, auricular chondritis is part of an immunemediated disorder termed relapsing polychondritis. This disease is characterised by inflammation, resulting in the destruction of multiple cartilaginous tissues and proteoglycan-rich organs. It often affects the ear and nose, and less frequently the eyes, larynx, vestibular and cardiovascular system. A similar condition with possible involvement of joints, eyes and heart was described in cats. In dogs, auricular chondritis remains a poorly defined condition. Our case did not show evident involvement of organs other than the ears, and the follow-up was too short (threemonths) to evaluate the possible relapsing nature of the disease.

在人类，耳软骨炎是一种免疫介导的疾病，称为复发性多软骨炎。这种疾病的特征是炎症，导致多个软骨组织和富含粘蛋白的器官的破坏。该病常累及耳和鼻，较少累及眼、喉、前庭和心血管系统。猫也有类似的情况，可能累及关节、眼睛和心脏。在犬上，耳软骨炎仍然是一个不明确的疾病。本例患犬除耳外未见明显器官患病，随访时间过短(3个月)，无法评估疾病可能的复发性质。

 

When compared with the only published case of canine auricular chondritis, this case shows not only several similarities but also some differences.Similarities include the age of the affected dog (middle-to-old-aged dog) and the rapid onset of erythema and nodular swelling of the concave aspect of the pinnae, preceded by intense pain. Differences include the fact that clinical signs were bilateral and much more severe in our case, and had persisted for longer (five months) than in the previously published case. In particular, the pinnae of the present case had lost their normal morphology and showed a nodular or ‘cauliflower’ appearance similar to the one described in people with auricular chondritis.

与文献报道的1例犬耳软骨炎病例相比，既有相似之处，也有不同之处。相似之处包括患犬的年龄(中老年犬)和迅速出现的耳廓凹面发红和结节性肿胀，随后出现剧烈疼痛。差异包括以下事实:本病例的临床症状是双侧的，严重得多，并且比之前发表的病例持续时间更长(5个月)。特别是，本病例的耳廓失去了正常的形态，并显示出类似于耳软骨炎患者的结节状或“菜花状”外观。

 

Images from CT scan in the present case also showed more obvious and extensive lesions, involving both the auricular and the annular cartilages, than the previously reported case, in which only a focal thickening of the pinna was observed. Clinical differential diagnoses for the nodular dermatitis of the pinnae in the present case included sterile pyogranulomatous dermatitis and panniculitis, idiopathic granulomatous sebaceous adenitis and sterile granulomatous dermatitis and lymphadenitis. However, these were considered to be unlikely owing to the lack of involvement of other areas of the body, and because they do not affect cartilage. Chronic proliferative otitis, end-stage OE and neoplasia also were considered improbable based on the sudden onset of clinical signs.

本病例的CT扫描图像也显示了更明显和更广泛的病变，包括耳廓和环状软骨，与之前报道的病例相比，在该病例中仅观察到局部耳廓增厚。在本病例中，耳廓结节性皮炎的临床鉴别诊断包括无菌性化脓性肉芽肿性皮炎和脂膜炎、特发性肉芽肿性皮脂腺炎和无菌性肉芽肿性皮炎和淋巴结炎。然而，由于缺乏身体其他部位患病，并且它们不影响软骨，因此被认为不太可能。慢性增生性耳炎、终末期OE和肿瘤也被认为是不可能的，基于突然出现的临床症状。

 

Confirmation of auricular chondritis requires the demonstration of auricular cartilage necrosis or degeneration surrounded by an inflammatory infiltrate. In the present case, a definitive diagnosis could not be established as a consequence of the lack of cartilage tissue in the histopathological sections. However, the pyogranulomatous inflammation and multifocal fibrosis were similar to those reported in canine, feline and human auricular chondritis. A surgical biopsy sample may have been more likely to identify chondritis. Finally, the resolution of pain and lesions with an immunosuppressive dose of prednisolone is in agreement with the previously reported case of canine auricular chondritis, yet the pinnal deformity and ear canal stenosis were unexpected sequelae. Deformity of the ear and closure of the external auditory meatus have been described in severe cases of human auricular chondritis. Different hypotheses can be formulated to explain the lack of response to ciclosporin, including the possibility that a longer treatment period might be required to see a more significant response.

确诊耳软骨炎需要显示耳廓软骨坏死或退变，周围有炎性浸润。在本病例中，由于组织病理学切片中缺乏软骨组织，无法确定诊断。然而，化脓性肉芽肿性炎症和多灶性纤维化与犬、猫和人耳软骨炎的报道相似。外科活检样本可能更有可能识别软骨炎。最后，使用免疫抑制剂量的泼尼松龙后，疼痛和病变的缓解与先前报道的犬耳软骨炎病例一致，但耳廓畸形和耳道狭窄是意外的后遗症。耳廓畸形和外耳道闭合已在人类耳廓软骨炎的严重病例中被描述。可以提出不同的假设来解释对环孢素无应答，包括可能需要更长的治疗期才能观察到更显著的应答。

 

In conclusion, this case supports previous observations that steroid-responsive painful nodular swelling of the pinna should raise suspicion for an inflammatory disease involving the auricular cartilage and shows for the first time the possible serious and irreversible consequences of such involvement. Further studies on a larger number of dogs with similar auricular abnormalities are needed.

总之，该病例支持之前的观察，即激素反应性耳廓痛性结节性肿胀应引起对累及耳廓软骨的炎症性疾病的怀疑，并首次显示这种累及可能的严重和不可逆的后果。我们需要在更多有类似耳廓畸形的犬身上进行进一步的研究。

 

 

 

 

 

 

FIGURE 1 Putative severe auricular chondritis in a dog. (a) Severe, diffuse multinodular swelling with ulcers of the pinna, extending into the ear canal and sparing the noncartilaginous margins. (b) The anatomical landmarks (tragus, antitragus and antihelix) of the pinna are no longer recognisable and the ear canal entrance is severely stenotic. The entrance of the ear canal is marked by the cotton swab.

图1一只犬推测为重度耳软骨炎(a)耳廓严重的弥散性多结节性肿胀伴溃疡，延伸至耳道，保留非软骨边缘。(b)耳廓的解剖标志(耳屏、对耳屏和对耳轮)不再可辨认，耳道入口严重狭窄。耳道入口用棉签标记。

 

 

FIGURE 2 Computed tomography (CT) images of the skull and the ears of the case Bolognese dog. (a) Transverse view from CT scan of the skull: pre-contrast with bone algorithm, showing lack of air in both ear canal and normal middle and inner ear structures. (b) Transverse view from CT scan of the skull (same slice as presented in a): postcontrast series with soft tissue algorithm. Note the thickening of both pinnae and the soft tissue of the external auricular canal containing a small amount of fluid. (c) Close view from the previous series, showing the irregular profile of the left pinna with areas of increased tissue density. The ROI 1 (region of interest) indicates a measure of the mean attenuation value of the tissue of 139 HU (Hounsfield Unit), which is higher than that of the rest of the pinna (ROI 2, mean value 41.46 HU). This feature is consistent with soft tissue inflammation. (d) Volume rendered CT views showing the irregular, nodular appearance of the auricular pinnae. Orange arrows indicate the cartilages of the pinnae and the auricular canal.

图2病例博洛尼亚犬的颅骨和耳部的计算机断层扫描(CT)图像(a)颅骨CT扫描横切面:骨密度对比，显示双耳道空气缺乏，中耳和内耳结构正常。(b)颅骨CT扫描横切面(同a层):软组织算法增强序列。请注意耳廓和外耳道软组织的增厚，其中含有少量液体。(c)上一个系列的放大图像，显示左侧耳廓的不规则轮廓，有组织密度增加的区域。ROI 1(感兴趣区域)表示组织的平均衰减值为139 HU(亨斯菲尔德单位)，高于其余耳廓的平均值(ROI 2，平均值为41.46 HU)。这一特征与软组织炎症相符。(d)显示耳廓软骨不规则结节状外观的容积渲染CT视图。橙色箭头表示耳廓软骨和耳道。

 

 

FIGURE 3 Histopathological findings of punch biopsies from the ear pinnae of a Bolognese dog with putative severe auricular chondritis. (a) Multinodular-to-diffuse pyogranulomatous infiltrate of the superficial and deep dermis. (b) Pyogranulomas (black arrow) and necrotic foci (black asterisks). (c) Double-trephine punch biopsy sample. The specimen includes the subcutis of the convex surface of the pinna (white star), the area where the cartilage should be (white arrow) and the skin of the convex surface of the pinna (black star).

图3推定患有重度耳软骨炎的博洛尼亚犬的耳廓打孔活检的组织病理学结果(a)真皮浅层和深层的多结节到弥散性化脓性肉芽肿浸润。(b)脓肿(黑色箭头)和坏死灶(黑色星号)。(c)双环钻活检样本。标本包括耳廓凸面的皮下组织(白星)，软骨应该在的区域(白色箭头)和耳廓凸面的皮肤(黑星)。

 

 

FIGURE 4 Resolution of pain and lesions after therapy with prednisolone. (a) The dog's head appears perfectly round owing to the drastic reduction in size of the pinnae. (b) After the resolution of lesions, the anatomical landmarks of the pinna and the entrance of the ear canal were no longer recognisable.

图4泼尼松龙治疗后疼痛和病变消退(a)由于耳廓的大小急剧缩小，犬的头显得非常圆。(b)病变消退后，耳廓和耳道入口的解剖标志不再可辨认。

杨先生