翻译：王帆
Background – Proliferative and necrotising otitis externa (PNOE) is a rare disorder in cats with poorly understood pathogenesis. Extra-auricular (EA) lesions recently have been mentioned in a textbook and in one case report.
Objectives – To describe EA lesions associated with PNOE in three kittens.
Animals – A 6-month-old female domestic short hair (DSH) cat (Case 1), an 8-month-old female DSH cat (Case 2) and a 5-month-old female DSH cat (Case 3).
Methods and results – All cases exhibited classical lesions of PNOE associated with EA lesions, generalised (cases 1 and 3) or limited to eyelids (Case 2). Lesions were characterised by thick, adherent, hyperkeratotic papules coalescing to plaques and attempts to remove the hyperkeratotic plaques resulted in erosions. Histopathological examinations revealed classical features of PNOE: severe acanthosis associated with a marked lymphocytic exocytosis, satellitosis and apoptotic keratinocytes at all levels of the epidermis and the outer root sheath of hair follicles. Cases 2 and 3 resolved spontaneously. Case 1 remained stable with topical tacrolimus and oral prednisolone after a short course of ciclosporin.
Conclusions and clinical importance – This report describes EA lesions of PNOE in three kittens. Such lesions may be underdiagnosed, and this report emphasises the role of a thorough clinical inspection in PNOE cases.
摘要
背景 – 增生性坏死性外耳炎(PNOE)是猫的一种罕见疾病, 对其发病机制知之甚少。最近在一本教科书和一份病例报告中提到了耳外(EA)病变。
目的 – 描述3只幼猫PNOE的EA病变。
动物 – 一只6月龄雌性家养短毛(DSH)猫(病例1)、一只8月龄雌性DSH猫(病例2) 和一只5月龄雌性DSH猫(病例3)。
方法和结果 – 所有病例均表现出PNOE的经典病变和EA病变,全身(病例1和3) 或仅限于眼睑(病例2)。病变的特征为厚的、粘附的、角化过度的丘疹融合成斑块, 试图清除角化过度的斑块会出现糜烂。组织病理学检查显示PNOE的典型特征为: 重度棘皮症伴所有表皮层和毛囊外根鞘明显的淋巴细胞外排、卫星现象和角质形成细胞凋亡。病例2和3自愈。病例1在外用他克莫司和口服泼尼松龙和短期使用环孢素治疗后能维持症状。
结论和临床意义 – 本报告描述了3只幼猫PNOE的EA病变。这些病变可能被漏诊,本报告强调了在PNOE病例中全面临床检查的重要性。
Introduction
介绍
Proliferative and necrotising otitis externa (PNOE) is a rare disorder in cats. The condition was first described in kittens, yet adult cats can be affected. The pathogenesis of this condition is still unknown; however, an immune-mediated disorder involving keratinocyte apoptosis by epidermal-infiltrating T cells is strongly suspected. PNOE lesions are classically symmetrical and affect the base of the pinna, the opening of the ear and the vertical ear canal. After being briefly mentioned in a textbook, extraauricular (EA) lesions have been described in one recent case report of PNOE. Herein, the authors document three new cases of PNOE with EA lesions.
增生性坏死性外耳炎(PNOE)是猫的一种罕见的疾病。这种疾病最初是在幼猫上发现的，但成年猫也会患病。其发病机制尚不清楚。但是，高度怀疑是一种T细胞浸润表皮层引起角质形成细胞凋亡的免疫介导性疾病。PNOE病变典型对称性，耳廓基部、耳道开口和垂直耳道患病。在教科书中有简述，近期一篇PNOE病例报告描述了耳外(EA)病变。在此，作者记录了3例PNOE合并EA病变的新病例。
Case history, diagnosis and treatment
病例的病史、诊断和治疗
Case 1
病例1
A 6-month-old female domestic short hair (DSH) cat was presented with a four month history of bilateral otitis. The cat had been vaccinated 10 days after the onset of the lesions. The kitten had received several subcutaneous injections of dexamethasone at 0.085 mg/kg (Dexamedium, MSD Sante Animale; Beaucouze, France) and oral marbofloxacin at 5 mg/kg/day (Marbocyl, Vetoquinol; Lure, France) for two months. At the time of presentation, the kitten was presumed to be in good health based on the lack of significant findings on physical examination. Dark keratinous debris overlying eroded vegetative plaques covered the proximal concave pinnae and the vertical ear canal of both ears(Figure 1a). Otoscopic examination was impossible. Ear cytological evaluation revealed a very mild yeast and bacterial overgrowth. Based on the suggestive clinical features and histopathological findings of samples collected from concave pinna, a diagnosis of PNOE was made. Topical 0.1 % tacrolimus (Protopic, LEO Pharma; Voisins-le-Bretonneux, France) was used once daily. One month later, the ear lesions were almost healed. However, new skin lesions had appeared. Numerous hyperkeratotic papules coalescing to plaques were found on the ventral abdomen, the ventral neck, the axillary and inguinal regions, and the medial aspect of the thighs (Figure 1b). Attempts to remove hyperkeratotic plaques resulted in erosions. The lesions were neither pruritic nor painful. Surface cytological evaluation did not show any yeast or bacterial infection. Examination of skin scrapings and plucked hairs did not reveal any fungal elements. Four skin biopsies from the abdomen and the ventral neck were performed. Histopathological features were similar to those found in PNOE which led to a diagnosis of EA lesions of PNOE. Ciclosporin (Cyclavance, Virbac; Carros, France) at 7 mg/ kg/day p.o. was added to topical tacrolimus. One month later, EA lesions were extending onto the head; hence, the ciclosporin dosage was increased to 10 mg/kg/day. Six weeks later, the ear and EA lesions had totally resolved. Unfortunately, the cat became aggressive during oral treatment administration which led to stopping the ciclosporin. Two weeks later, the PNOE and not the EA lesions relapsed. Daily topical tacrolimus was resumed and systemic prednisolone (1 mg/kg/day p.o.) were added. PNOE healed again and remained in remission under treatment.
一只6月龄的雌性家养短毛(DSH)猫有4个月的双侧耳炎病史。这只猫在发病10天后接种了疫苗。幼猫曾用过多次皮下注射0.085 mg/kg的地塞米松和口服马波沙星5mg/kg/天，连续两个月。首诊时，幼猫体格检查未见明显异常，健康状况良好。可见双耳耳廓凹面基部和垂直耳道，紧紧覆盖着有深色角质碎片的糜烂性斑块(图1a)。无法进行检耳镜检查。耳道细胞学检查显示非常轻微的酵母菌和细菌过度增殖。根据临床特症状提示和耳廓凹侧采样的组织病理学表现，确诊为PNOE。外用0.1%他克莫司每天一次。一个月后，耳部病变基本愈合。但是，出现了新的皮肤病变。在腹底、颈腹侧、腋窝和腹股沟区以及大腿内侧可见大量角化过度丘疹合并成斑块(图1b)。试图去除角化过度斑块会导致糜烂。病变既不瘙痒也不疼痛。表面细胞学检查没有发现酵母菌或细菌感染。对皮肤刮片和毛发检查没有发现任何真菌元素。从腹部和颈腹侧进行四处皮肤活检采样。组织病理学特征与PNOE相似，诊断为PNOE的EA病变。使用环孢素，口服剂量为7 mg/ kg/日，联用他克莫司外用。1个月后，EA病变扩展至头部，因此，环孢素剂量增加到10mg /kg/日。6周后，耳部和EA病变完全消失。不幸的是，在口服治疗期间，这只猫变得有攻击性，导致停用环孢素。两周后，PNOE的非EA病变复发。恢复每日外用他克莫司，并全身使用泼尼松龙(1 mg/kg/日口服)。PNOE再次恢复，在治疗时病变持续缓解。
Figure 1. Feline proliferative and necrotising otitis externa in a 6-month-old female domestic short hair cat with generalised extra-auricular lesions (Case 1).
（a）Well-demarcated erythematous plaques with adherent, thick dark to brown keratinous debris are present in the medial aspect of the pinna, the entrance to the auditory canal. (b) Thick, hyperkeratotic plaques on the ventral abdomen.
图1。一只6月龄的雌性家养短毛猫患增生性坏死性外耳炎，伴有全身性耳外病变(病例1)。
(a)在耳廓内侧耳道开口处可见界限清晰的红斑性斑块，伴有粘附的、厚的、深色到棕色的角质碎片。(b)腹底有厚的角化过度的斑块。
Case 2
病例2
An 8-month-old female DSH cat was presented with a four week history of bilateral otitis and blepharitis. Vaccination and medical histories were unknown. The kitten appeared in good health based on lack of significant findings on physical examination. White to brown thick keratinous plaques covered the proximal concave pinnae and the vertical ear canal of both ears, and thick dark keratinous debris covered both eroded eyelids (Figure 2a,b). Surface cytological examination was unremarkable. Three skin biopsies were obtained from the concave pinnae and the eyelids. Histological findings led to the diagnosis of PNOE with EA distribution. Although topical tacrolimus was prescribed, during a routine vaccination visit six months later, the owners reported that they had not purchased the treatment. Therefore, all ear and eyelid lesions had healed spontaneously.
一只8月龄的雌性DSH猫有4周的双侧耳炎和睑炎病史。免疫史和用药史不详。幼猫体格检查未见明显异常，健康状况良好。双耳耳廓凹面基部和垂直耳道覆盖着白色至棕色厚的角质斑块，双侧糜烂的眼睑覆盖着厚的深色角质碎片(图2a,b)。表面细胞学检查无明显异常发现。从耳廓凹陷面和眼睑进行三处皮肤活检采样，组织学结果确诊为PNOE伴有EA病变。虽然医生建议外用他克莫司，但在6个月后的常规疫苗接种回访期间，宠主说他们没有购买药和治疗。因此，所有耳部和眼睑病变都已自愈。
Figure 2. Feline proliferative and necrotising otitis externa in an 8-month-old female domestic short hair cat with extra-auricular lesions found on the eyelids (Case 2).
（a）White to brown thick keratinous plaques cover the proximal concave pinnae and the vertical ear canal. (b) Thick dark keratinous debris covers both eroded eyelids.
图2。一只8月龄的雌型家养短毛猫患猫增生性坏死性外耳炎，眼睑上发现耳外病变(病例2)。
(a)耳廓凹面基部和垂直耳道可见白色至棕色的厚的角质斑块覆盖。(b)糜烂的眼睑上覆盖着厚的深色角质碎片。
Case 3
病例3
A 5-month-old female DSH cat was presented with bilateral otitis and skin lesions for 10 days. The cat was not vaccinated and had not received any medications before the onset of the lesions. The kitten was presumed to be in good health based on lack of significant findings on physical examination. Characteristic erythematous, thick, dark, hyperkeratotic plaques were observed at the entrance of both auditory canals (Figure 3a). Concurrent bacterial or yeast otitis was not reported. As in Case 1, numerous hyperkeratotic papules coalescing to eroded plaques were found mostly on the eyelids and the face (Figure 3b), and also on the perineum. Gentle manipulation of the debris revealed underlying erosions and ulcers. The lesions were neither pruritic nor painful. Surface cytological examination was unremarkable. A diagnosis of EA lesions of PNOE was made based on clinical and histological findings for samples collected from concave pinnae and cheek lesions. The lesions had started to heal spontaneously when histopathological results arrived. No therapy was initiated, and we advised the owners to closely monitor the cat. Two months later, the cat was free of lesions and no recurrence has occurred at the time of writing.
一只5月龄的雌性DSH猫出现双侧耳炎和皮肤病变10天。在首次发病前猫没有免疫史，也没有用药史。幼猫体格检查未见明显异常，健康状况良好。外侧耳道开口可见特征性的红斑、厚的、深色、角化过度的斑块(图3a)。未见并发细菌性或酵母菌性耳炎。与病例1一样，眼睑和面部，也见于会阴部多见大量角化过度丘疹合并成糜烂性斑块(图3b)。轻轻去除碎片，可见下方糜烂和溃疡。病变既不瘙痒也不疼痛。表面细胞学检查无明显异常。根据临床和耳廓凹面和脸颊病变皮肤活检采样的组织学检查确诊为PNOE及EA病变。当得到组织病理学结果时，病变已经开始自愈。最初没有治疗，我们建议宠主密切关注患猫。两个月后，猫病变消失，并且写此文章时患猫没有复发。
Figure 3. Feline proliferative and necrotising otitis externa in a 5- month-old female domestic short hair cat with generalised extra-auricular lesions (Case 3).
(a) Well-demarcated erythematous plaques with adherent, thick dark to brown keratinous debris are present in the medial aspect of the pinna, the entrance to the auditory canal. (b) Thick, hyperkeratotic papules and plaques on the eyelid and the face (arrows).
图3。一只5月龄的雌型家养短毛猫患猫增生性坏死性外耳炎，伴有全身性耳外病变(病例3)。
(a)在耳廓内侧耳道开口处可见界限清晰的红斑性斑块，并有粘附的、厚的、暗色到棕色的角质碎片。(b)眼睑和面部有厚的角化过度的丘疹和斑块(箭头)。
Histopathological and immunohistochemical methods and findings
组织病理学和免疫组化方法和结果
The samples were fixed in 10% neutral buffered formalin, routinely processed, sectioned at 5 μm and stained with haematoxylin & eosin. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue for CD3 (monoclonal rat anti-human CD3, Bio-Rad laboratories Inc.; Hercules, CA, USA). Histological examination was essentially identical for all three cases, apart from a less intense inflammatory infiltrate in the EA lesions of Case 3. All samples demonstrated classic features observed in PNOE (Figure 4a,b). There was marked epidermal hyperplasia that extended to involve follicular infundibula, and a marked surface and follicular parakeratotic hyperkeratosis mixed with neutrophilic crusts. A marked lymphocytic exocytosis and superficial apoptotic keratinocytes were observed at all levels of the epidermis and outer root sheath of follicular infundibulum, some lymphocytes surrounding apoptotic keratinocytes (satellitosis). The superficial dermis was oedematous and the vessels were dilated. A perivascular to diffuse inflammatory infiltrate, which consisted mainly of lymphocytes, and small numbers of mast cells, macrophages, plasma cells and neutrophils was present in the dermis. Periodic acid Schiff staining did not reveal any fungalelement. Immunohistochemical evaluation revealed that the infiltrating lymphocytes were predominantly CD3+ T cells (Figure 4c).
样品在10%中性福尔马林缓冲液中固定，常规处理，切片5μm，苏木精伊红染色。对福尔马林固定石蜡包埋的组织进行CD3免疫组化染色。除了病例3的EA病变有较轻的炎症浸润外，三个病例的组织学检查基本相同。所有样本均表现出PNOE中观察到的典型特征(图4a,b)。有明显的表皮层增生，延伸到毛囊漏斗部，并有明显的浅表和毛囊角化不全性角化过度，并伴有中性粒细胞性结痂。所有表皮层和毛囊漏斗部外根鞘可见明显的淋巴细胞外排和浅表角质形成细胞凋亡，部分淋巴细胞围绕凋亡的角质形成细胞(卫星现象)。真皮浅层水肿，血管扩张。真皮内可见血管周围弥散性炎症浸润，以淋巴细胞为主，少量肥大细胞、巨噬细胞、浆细胞和中性粒细胞。过碘酸希夫染色未发现任何真菌元素。免疫组化评价显示浸润淋巴细胞以CD3+T细胞为主(图4c)。
Figure 4. Histopathological and immunohistochemical findings in skin biopsies from extra-auricular lesions of proliferative and necrotising otitis externa in a kitten (Case 1).
(a,b) A marked epidermal hyperplasia that extended to involve follicular infundibula, and a marked parakeratotic hyperkeratosis were observed.
Parakeratosis often involved the follicular infundibulum. A marked lymphocytic exocytosis and apoptotic keratinocytes (arrows) were observed at all levels of the epidermis and outer root sheath of follicular infundibulum, some lymphocytes surrounding apoptotic keratinocytes. Haematoxylin & eosin, x50 (a), x400 (b). (c) Immunohistochemical examination revealed that the infiltrating lymphocytes were predominantly CD3+ T cells, x400.
图4。幼猫增生性坏死性外耳炎的耳外病变的皮肤活检组织病理学和免疫组化结果(病例1)。(a,b)观察到明显的表皮层增生，延伸到毛囊漏斗部，有明显的角化不全性角化过度。角化不全常累及毛囊漏斗部。所有表皮层和毛囊漏斗部外根鞘可见明显的淋巴细胞外排和角质形成细胞凋亡(箭头)，部分淋巴细胞围绕凋亡的角质形成细胞。苏木精伊红染色，50倍放大（a），100倍放大（b）。(c)免疫组化检查显示主要以CD3+T细胞为主的淋巴细胞浸润，400倍放大。
Discussion
讨论
In this report we describe three new cases of EA lesions associated with PNOE in kittens. Frequency of such EA lesions is unknown although they have been mentioned recently in a textbook and in a case report. The case reported by MacAuliffe et al. was an 8-week-old male DSH kitten with strikingly similar lesions: diffuse, thick, well-demarcated dark surface crusting restricted to the face. The skin beneath the crusts also was eroded. Unlike our cases, lesions were very pruritic and although the kitten had otitis externa, it was not proliferative or necrotic. Interestingly, the EA lesions in Case 1 developed five months after the onset of PNOE, whereas EA developed simultaneously with PNOE for the other kittens.
在这篇报告中，我们描述了三个幼猫PNOE新病例的EA病变。虽然这种EA病变的发病率未知，但是最近在一本教科书和一个病例报告中有报道。MacAuliffe等人报道的病例是一只8周龄的雄性DSH幼猫伴有非常相似的病变:局限于面部的弥散性、厚的、边界清楚的深色浅表结痂。结痂下皮肤也有糜烂。与我们病例不同的是，病变非常瘙痒，虽然幼猫有外耳炎，但未发生增生或坏死。有趣的是，病例1中EA病变发生在PNOE发病5个月后，而其他幼猫EA病变与PNOE同时发生。
Diagnosis of PNOE is usually straightforward as the clinical signs are very suggestive. However, EA lesions are peculiar, and histopathological examination is essential to eliminate differential diagnosis such as pemphigus foliaceus, papillomavirus-associated feline Bowenoid carcinoma in situ, papilloma or, less likely, dermatophytosis. The histological changes were nearly identical in our three cases and the one from MacAuliffe et al. Moreover, EA biopsy specimens exhibited the exact same features as in PNOE.
PNOE的诊断通常很简单，因为临床症状具有高度提示。但是，EA病变很特殊，必须进行组织病理学检查，以排除鉴别诊断，如落叶型天疱疮、乳头瘤病毒相关的猫鲍文样原位癌、乳头状瘤或较不常见的皮肤癣菌病。我们的三个病例和MacAuliffe等人的一个病例的组织学变化几乎相同。此外，EA活检样本特征显示与PNOE完全相同。
The pathogenesis of PNOE is poorly characterised; lesions exhibit a T-cell-mediated keratinocyte apoptosis. Similar features were found in EA lesions with predominantly CD3+ T cells infiltrating all levels of the epidermis and outer root sheath of hair follicles and superficial apoptotic keratinocytes. Interestingly, EA lesions were clinically and histopathologically similar to those found in the hyperkeratotic erythema multiforme (HKEM) of dogs in which erosive and hyperkeratotic lesions are linked to an analogous cytotoxic attack on keratinocytes by T cells.Unlike PNOE, which affects mostly kittens and has a good prognosis, HKEM affects dogs in their mid- to late adulthood and is considered refractory to treatment with low remission rates reported with glucocorticoids and/or ciclosporin.
PNOE的发病机制尚不明确。病变表现为T细胞介导的角质形成细胞凋亡。在EA病变中也发现了类似的特征，主要是CD3+T细胞浸润了所有表皮层和毛囊外根鞘和浅表角质形成细胞凋亡。有趣的是，EA病变在临床和组织病理学上与犬的角化过度型多形红斑(HKEM)相似，其中糜烂性和角化过度病变与T细胞对角质形成细胞的类似细胞毒性攻击有关。PNOE主要幼猫患病，预后良好。与PNOE不同，HKEM是中年至老年犬患病，治疗有难度，使用糖皮质激素和/或环孢素治疗效果低。
The prognosis of PNOE is generally good. In these three reports, EA lesions behaved in a similar way to PNOE. Some cases may resolve spontaneously, and some may need long-term therapy. However, the kitten with severe facial lesions reported by MacAuliffe et al. deteriorated rapidly and developed severe azotaemia from unknown origin which led to euthanasia. Considering the lymphocyte-mediated pathogenesis, calcineurin inhibitors are the first choice for treatment and several cases have been well-controlled with topical tacrolimus alone. However, some cases have been controlled by topical and systemic glucocorticoids. Ciclosporin was added to topical tacrolimus in Case 1 as lesions were generalised.
PNOE的预后一般良好。在这三份报告中，EA病变的表现与PNOE相似。有些病例可能会自行痊愈，有些可能需要长期治疗。然而，MacAuliffe等报道的面部严重病变的幼猫迅速恶化，发展为不明原因的严重氮血症，最终导致安乐死。考虑到淋巴细胞介导的发病机制，钙调磷酸酶抑制剂是治疗的第一选择，一些病例已经通过外用他克莫司得到很好的控制。但是，一些病例通过外用联合全身糖皮质激素治疗得到控制。病例1因为病变为全身性所以外用他克莫司联用环孢素进行治疗。
These three cases document EA lesions in PNOE and emphasise the role of a thorough clinical inspection in PNOE cases. Prognosis for recovery appears to range from good to guarded.
这三个病例记录了PNOE的EA病变，并强调了在PNOE病例中全面的临床检查的重要性。治疗预后似乎从良好到谨慎不等。
|Archiver|手机版|小黑屋|宠医帮
( 京ICP备2022012070号-2 ) 
发表于 2021-5-11 23:12:48
收藏
转播
分享
淘帖
