除皱术(外科面部除皱术)和荧光光生物调节治疗犬眼周皮炎:病例报 ...

王帆

Treatment of canine periocular dermatitis with rhytidectomy (surgical face-lift) and fluorescence photobiomodulation: A case report

除皱术(外科面部除皱术)和荧光光生物调节治疗犬眼周皮炎:病例报告

 

翻译：朱锋 校对：王帆

Abstract

Canine periocular dermatitis may be associated with excessive facial folds and heavy brows (EFF-HB). There is no gold standard therapy for EFF-HB-associated periocular dermatitis, and conventional medical management may fail. Herein, we describe periocular fluorescence photobiomodulation and rhytidectomy as novel approaches to treat EFF-HB-associated periocular dermatitis refractory to medical management.

摘要

犬眼周皮炎可能与面部皱纹过多和眉毛过重（heavy brows）相关 (EFF-HB)。EFF-HB相关的眼周皮炎尚无金标准的治疗方案，常规药物治疗可能失败。在此，我们描述了眼周荧光光生物调节和除皱术，作为治疗药物治疗无效的EFF-HB相关眼周皮炎的新方法。

 

KEYWORDS

关键词

canine, fluorescence photobiomodulation, intertrigo, ophthalmology, periocular dermatitis, rhytidectomy

犬，荧光光生物调节，皮褶炎，眼科，眼周皮炎，除皱术

 

INTRODUCTION

介绍

Canine periocular dermatitis has been associated with numerous conditions, including allergic dermatoses, primary eyelid diseases, infections, parasitic infestations, autoimmune disorders, neoplasia, endocrinopathy and adverse drug reactions. Excessive facial folds and heavy brows (EFF-HB), although desirable in breeds such as the Saint Bernard, also may be associated with periocular dermatitis by inciting or exacerbating ophthalmic and dermatological diseases. Ophthalmologically, EFF-HB can affect eyelid position, leading to ectropion, entropion, euryblepharon and trichiasis, with secondary blepharitis and epiphora. Periocular dermatitis may develop as an extension of blepharitis or from chronic wetting from epiphora and ophthalmic topical medications. Dermatologically, periocular skin folds may develop intertrigo. Pathogenesis is likely to involve frictional irritation, heat, decreased air circulation, and accumulated tears, sebum and ophthalmic medications within apposed skin folds; these factors create microenvironments that favour inflammation and overgrowth of bacteria or yeast.

 

犬眼周皮炎与多种疾病相关，包括过敏性皮肤病、原发性眼睑疾病、感染、寄生虫感染、自身免疫性疾病、肿瘤、内分泌疾病和药物不良反应。虽然在有些犬种中希望能拥有（desirable）过多的面部皱褶和眉毛过重(EFF-HB)的外观，比如圣伯纳犬，但这种也可能刺激或加重眼科和皮肤病而出现眼周皮炎。眼科方面，EFF-HB可影响眼睑位置，导致睑外翻、内翻、巨睑裂和倒睫，可继发睑炎和泪溢。眼周皮炎可能发展为睑炎的延伸，或由泪溢和眼外用药引起的慢性潮湿浸渍。在皮肤方面，眼周皮肤皱褶可能形成皮褶炎。发病机制可能涉及摩擦刺激、发热、空气循环减少，以及在皮肤皱褶内积聚泪液、皮脂和眼科药物；这些因素创造了有利于炎症和细菌或酵母过度增殖的微环境。

 

There is no gold standard therapy for EFF-HB associated periocular dermatitis. Blepharoplastic surgeries may improve periocular dermatitis by correcting concurrent eyelid disease yet carry a higher risk of postoperative complications in the presence of periocular infections. Medical management for intertrigo of any anatomical site involves controlling microbial overgrowth, moisture, and any predisposing or perpetuating factors; however, medical management usually is symptomatic and may be unrewarding. Intertrigo cannot be cured without the elimination of the problematic skin folds, which may require surgical resection.

EFF-HB相关眼周皮炎尚无金标准治疗方案。眼睑整容术可以通过矫正并发的眼睑疾病来改善眼周皮炎，但存在眼周感染时，术后并发症的风险较高。针对各种部位的皮褶的医疗处置包括控制微生物过度增殖、湿度和任何易感或持久因素。然而，药物治疗通常只是对症治疗，可能没有效果。如果不消除有问题的皮肤皱褶，皮褶炎就无法治愈，就可能需要手术切除。

 

Rhytidectomy (face-lift) involves the resection of excessive facial skin and is a treatment for canine ectropion, entropion and euryblepharon associated with EFF-HB. By reducing skin folding and correcting eyelid disease, rhytidectomy also may improve periocular dermatitis; however, this has not been evaluated to date.

除皱术(面部除皱术)涉及切除面部过多的皮肤，是一种治疗与EFF-HB相关的犬眼睑外翻、眼睑内翻和巨睑裂的方法。通过减少皮肤皱褶和矫正眼睑疾病，除皱术也可能改善眼周皮炎。然而，迄今为止尚未对此进行评估。

 

Fluorescence photobiomodulation (FBM) (Phovia; Vetoquinol) is an effective adjunct to therapy of canine pyoderma, interdigital furunculosis, perianal fistulae and wound healing (including surgical incisions). With FBM, blue light (440–460nm) from a light-emitting diode (LED) activates a photoconverter gel applied to the skin. Specialised chromophores in the gel generate fluorescence with localised effects: downregulated tumour necrosis factor α; upregulated epidermal growth factor, fibroblast growth factors, transforming growth factor beta, collagens I and III, Ki67, factor VIII and decorin; and increased mitochondrial size and number. These result in antibacterial, wound healing and biomodulatory (epithelialisation, angiogenesis and inflammatory) properties. Therefore, FBM is a treatment that may reduce reliance on the use of antimicrobials and support antimicrobial stewardship, while causing neither systemic adverse effects nor increased burden on owners for at-home treatment compliance. Use of FBM periocularly has not been reported in dogs. Considerations include inadvertent intraocular placement of photoconverter gel (for which ocular safety has not been reported), visual discomfort from the fluorescent light, and blue light damage to the retina and photoreceptor cells.
荧光光生物调节(FBM) (肤维安)是一种有效的辅助治疗犬脓皮病、趾间疖病、肛周瘘和伤口愈合(包括手术切口)的方法。使用FBM，来自发光二极管(LED)的蓝光(440-460nm)激活皮肤上的光转换凝胶。凝胶中特定的发光团产生荧光并具有局部效应:下调肿瘤坏死因子α;上调表皮生长因子、成纤维细胞生长因子、转化生长因子β、I型和III型胶原、Ki67、因子VIII和核心蛋白聚糖;线粒体的大小和数量增加。它们具有抗菌、伤口愈合和生物调节(上皮化、血管生成和炎症)的特性。因此，FBM是一种可能减少对抗菌药物使用的依赖并支持抗菌药物管理的治疗方法，同时既不会造成全身性不良反应，也不会增加宠主的家庭治疗依从性负担。在犬的眼周应用FBM尚未见报道。考虑因素包括担心光转换凝胶不小心接触眼睛(眼部安全性尚未报告)、荧光引起的视觉不适，以及蓝光对视网膜和光感受器细胞的损伤。

 

This report describes the successful use of rhytidectomy to treat EFF-HB-associated canine periocular dermatitis resistant to medical management. It additionally describes a protocol for periocular FBM administration.

本报告描述了成功使用除皱术治疗药物治疗无效的EFF-HB相关犬眼周皮炎。另外还描述了眼周FBM给药的方案。

 

CASE REPORT

病例报告

A 2-year-old female spayed Saint Bernard dog with EFF-HB was presented for periocular dermatitis, entropion, euryblepharon and trichiasis. The history included intermittent otitis externa, and pruritus of the feet and perivulvar areas, suggestive of mild allergic skin disease. Blepharoplasty was proposed by a veterinary ophthalmologist yet postponed owing to the severity of periocular dermatitis, prompting dermatological firstopinion referral.

1例2岁雌性已绝育圣伯纳犬患EFF-HB，表现为眼周皮炎、眼球内翻、巨睑裂和倒睫。病史包括间歇性外耳炎，以及足部和外阴周围区域瘙痒，提示轻度过敏性皮肤病。一名兽医眼科医师提出了眼睑整容术，但由于眼周皮炎的严重程度而推迟，提出转诊至皮肤科。

 

Dermatological evaluation revealed deep and inflamed facial folds, particularly periocularly. There was a wide band of periocular intertriginous and eyelid erythema, crusting, multifocal ulceration and brown hair discoloration. The ear canals, perivulvar skin and interdigital regions were mildly erythematous. Results of a complete blood count, serum chemical panel, urinalysis, thyroid hormone panel and deep skin scrapings were unremarkable. Cytological examination of periocular impression smears revealed coccoid and rod-shaped bacteria within neutrophils, consistent with pyoderma. Periocular intertrigo, eyelid disease (entropion, euryblepharon, trichiasis) and chronic wetting (epiphora, ophthalmic medications) in combination with mild allergic dermatitis were suspected to be predisposing, precipitating, and perpetuating factors which contributed to the skin infection.

皮肤科医生评估发现面部褶皱深且有炎症，尤其是眼周。眼周有宽条眼周皮褶炎及眼睑皮肤发红、结痂、多灶性溃疡及毛发变棕色。耳道、外阴周围皮肤及趾间轻度发红。全血细胞计数、血生化、尿液分析、甲状腺功能检查和和深层皮肤刮片的结果均无明显异常。眼周压片的细胞学检查显示，中性粒细胞内有球菌和杆菌，符合脓皮病表现。眼周皮褶炎、眼睑疾病(睑内翻、巨睑裂、倒睫)和慢性潮湿浸渍(泪溢、眼科药物)合并轻度过敏性皮肤病被怀疑是皮肤感染的易感、促发和持久因素。

 

Empirical therapy with oral cefpodoxime 8.8mg/kg once daily for fourweeks with topical chlorhexidine-based wipes (TrisOphtho; Dermazoo) produced an insufficient response. Based on aerobic bacterial culture and sensitivity testing, which demonstrated growth of Pseudomonas aeruginosa and beta-haemolytic Streptococcus spp. and which corroborated cytological findings, oral marbofloxacin (Zeniquin; Zoetis) 2.9 mg/ kg once daily then was prescribed. Treatment persisted for fourweeks and produced an insufficient response. Investigations to identify an underlying allergic disease then were recommended and declined. For empirical treatment of pruritus, the owner elected to try oral oclacitinib (Apoquel; Zoetis) at a dose of 0.4mg/kg twice daily for 14 days, then once daily for two months. When this treatment regimen was ineffective, once daily oral ciclosporin (modified) at a dose of 3mg/kg combined with ketoconazole at 3mg/kg once daily were administered. While other signs of allergic dermatitis (otic, interdigital and perivulvar erythema) responded well, periocular dermatitis persisted. Two months later, the primary veterinarian diagnosed acute hepatopathy based on hyperbilirubinemia and elevated alkaline phosphatase, and discontinued ciclosporin and ketoconazole on suspicion of adverse drug reaction.The owner subsequently was reluctant to administer further systemic therapy, motivating investigation of alternatives.

经验性治疗:口服头孢泊肟8.8mg/kg，每日1次，连续4周，外用氯己定湿巾治疗无效。根据需氧细菌培养和药敏试验证实了铜绿假单胞菌和β溶血性链球菌属的生长，并证实了细胞学结果，口服马波沙星2.9 mg/kg, 每日一次。治疗持续4周，但治疗无效。建议对潜在过敏性疾病进行调查，但被拒绝。对于瘙痒的经验性治疗，宠主选择尝试口服奥拉替尼，0.4mg/kg/次，bid，用药14天，然后每天1次，用药2个月。治疗无效时，给予环孢素(改良)3mg/kg口服，每日一次，联合酮康唑3mg/kg口服，每日一次。虽然过敏性皮肤病的其他症状(耳部、趾间和外阴周围皮肤发红)反应良好，但眼周皮炎持续存在。2个月后，首诊兽医根据高胆红素血症和碱性磷酸酶升高诊断为急性肝病，因怀疑药物不良反应停用环孢素和酮康唑。随后，宠主不愿接受进一步的全身性治疗，这促使研究寻找替代方案。

 

 

 

FIGURE 1 The Delasco Cox II metal corneal shield (a) ex vivo and (b) after placement on the patient's left eye before fluorescence biomodulation. The red arrow points to the grey shield over the eye; the blue arrow points to a small handle that facilitates the manipulation of the shield.

图1 Delasco Cox II金属角膜保护罩(a)体外照片，(b)放入患犬左眼后，荧光生物调节治疗之前照片。红色箭头指向盖在眼睛上的灰色保护罩;蓝色箭头指向一个便于操作保护罩的小手柄。

 

 

FBM was presented as a therapy established for the management of canine pyoderma which had not yet been evaluated for periocular application. With owner consent, a light-blocking, metal corneal shield (Cox II Laser Corneal Eye Shield; Delasco) was applied to prevent inadvertent administration of gel or light intraocularly. The eye was prepared with topical proparacaine hydrochloride ophthalmic solution 0.5%; one drop was administered onto the eye every five-minutes for three doses to produce analgesia, then sterile ophthalmic lubricant was placed on the shield's concave surface and the shield applied with gloved hand over the cornea (Figure 1).A 2mm layer of photoconverter gel was applied to the affected periocular and eyelid skin, and the Phovia system's specialised, handheld, LED lamp was focused on the treated skin at a 5 cm distance for two-minutes. The gel was removed using sterile gauze which had been immersed in sterile ophthalmic saline solution, followed by a one-minute rest period, after which the process was repeated. Following FBM, residual gel was removed using wetted gauze and copious flushing with sterile saline solution before removing the shield. There was 90% cytological reduction of bacteria and subjective clinical improvement after four weekly treatments, yet infection relapsed during Week 5 (Figure 2).

FBM是一种用于治疗犬脓皮病的治疗方法，尚未评估其在眼周的应用。经宠主同意，使用一种阻挡光线的金属角膜护罩，以防止凝胶或光不小心接触眼睛。外用0.5%盐酸丙美卡因滴眼液;每5分钟滴一滴到眼睛上，共3次，以产生镇痛效果，然后将无菌的眼科润滑剂放置在防护罩的凹面上，并用手套手将防护罩盖在角膜上(图1)。将2mm的光转换凝胶涂在患病眼周和眼睑皮肤上，肤维安的专用手持式LED灯在治疗的皮肤上方5cm照射，持续2分钟。将无菌纱布浸泡于无菌眼用生理盐水中以去除凝胶，休息1 min后重复上述操作。FBM治疗后，用湿纱布和无菌生理盐水大量冲洗去除残留的凝胶，然后移除角膜保护罩。每周一次，治疗4周后，细胞学检查发现细菌减少了90%，主观临床改善，但感染在第5周期间复发(图2)。

 

Rhytidectomy subsequently was presented as an established therapy for EFF-HB-associated eyelid diseases, which theoretically also could improve periocular dermatitis by reducing excessive skin folding and correcting eyelid pathological impacts. Unlike blepharoplasty, coronal rhytidectomy would involve dorsal head incisions, avoiding infected periocular/eyelid skin. With client consent, coronal rhytidectomy was performed by a veterinary surgeon.Under general anaesthesia, redundant coronal (dorsal head) skin was excised, and the remaining skin edges apposed, effectively retracting the facial skin, reducing periocular folds and adjusting eyelid position (Figure 3). Postoperative care involved an E-collar, oral gabapentin 9.8mg/kg every eight hours for two weeks, and a three-day transdermal patch which delivered fentanyl at a rate of 1.6μg/kg/h.

随后，除皱术被提出作为一种治疗EFF-HB相关眼睑疾病的有效方法，它也可以通过减少过度的皮肤褶皱和纠正眼睑的病理性影响来改善眼周皮炎。与眼睑成形术不同，头部除皱术涉及头部背侧切口，避开眼周/眼睑感染的皮肤。经宠主同意，由外科医生进行头部除皱术。在全身麻醉下，切除多余的头部(头背部)皮肤，将剩余的皮肤边缘缝在一起，有效地收缩面部皮肤，减少眼周皱褶，调整眼睑位置(图3)。术后护理包括佩戴伊丽莎白项圈，每8小时口服加巴喷丁9.8mg/kg，持续两周，并使用透皮贴剂的芬太尼1.6μg/kg/h给药3天。

 

Six weeks postoperatively, periocular dermatitis, entropion and trichiasis had resolved with residual mild brown hair discoloration (Figure 4). There was no relapse of dermatological signs or development of intraocular disease over a nine-month period of follow-up.

术后6周，眼周皮炎、睑内翻和倒睫消退，残留轻度棕色毛发变色(图4)。在9个月的随访期间，皮肤症状未复发，未发生眼内疾病。

 

Figure 2 Progression of the right periocular dermatitis and blepharitis (a) before fluorescence photobiomodulation, (b) after four weekly treatments with fluorescence photobiomodulation, and (c) at the time of rhytidectomy (relapse of periocular dermatitis and blepharitis). Photographs were taken by manually retracting the excessive periocular skin folds to allow visualisation of the eye.

图2右侧眼周皮炎和睑缘炎的进展情况：(a)荧光光生物调节治疗前，(b)荧光光生物调节治疗4周后，以及(c)在除皱术时(眼周皮炎和睑炎复发)。拍照时通过手动把眼周褶皱皮肤拉平，以便看清眼睛的状况。

 

Figure 3 The extent of redundant skin excised from the patient's dorsal head during rhytidectomy.

图3除皱术中从患病动物的头背部切除的多余的皮肤。

 

Figure 4 Progression of the surgical incision, eyelid placement and periocular dermatitis (a) 24h post-rhytidectomy and (b) six weeks post-rhytidectomy. Note improvement in periocular dermatitis, brown periocular staining and blepharitis without additional therapy.

图4手术切口、眼睑位置和眼周皮炎的进展：(a)除皱术后24小时以及(b)除皱术后6周。注意在不接受其他治疗的情况下，眼周皮炎、眼周棕色染色和睑炎有所改善。

 

 

DISCUSSION

讨论

This is the first report describing the efficacy of rhytidectomy for EFF-HB-associated periocular dermatitis and pyoderma. While rhytidectomy has been described for EFF-HB-associated canine ectropion, entropion and euryblepharon, we demonstrate that rhytidectomy also may be a part of a therapeutic protocol for periocular dermatitis and pyoderma by reducing skin-fold redundancy and correcting eyelid disease.

这是第一份描述除皱术治疗EFF-HB相关眼周皮炎和脓皮病疗效的报告。虽然除皱术已被描述为EFF-HB相关的犬眼睑外翻、内翻和巨睑裂，但我们证明除皱术也可以通过去除皮肤褶皱和纠正眼睑疾病，成为眼周皮炎和脓皮病治疗方案的一部分。

In this dog, concurrent allergic skin disease may have contributed to the periocular dermatitis, although immunomodulatory therapies alone were insufficient. The best response was achieved with rhytidectomy, supporting the role of EFF-HB. However, we feel it is important to emphasise that medical management to address any predisposing, precipitating, or perpetuating factors should be pursued before considering a surgical approach.

该犬并发的过敏性皮肤病可能导致了眼周皮炎，但单独的免疫调节疗法是不够的。除皱术的效果最好，支持了EFF-HB的作用。然而，我们认为有必要强调的是，在考虑手术治疗之前，应进行药物治疗，以解决任何易感、促发或持久因素。

Apart from scarring, complications of rhytidectomy were not seen in this case. Complications may include postoperative infections, dehiscence, negatively altered cosmesis, facial nerve impairment, haematomas and an inadequate blink response if excessive tissue is excised. While not performed here, the application of FBM to the surgical incision could potentially expedite postoperative healing.

除形成瘢痕外，本组未见除皱手术并发症。并发症可能包括术后感染、皮肤裂开、美容效果的负面改变、面神经损伤、血肿和如果切除过多的组织，眨眼反应不足。虽然本病例手术切口并没有使用FBM，但手术切口使用FBM可能会加快术后愈合。

This report also describes a safe and feasible protocol for periocular FBM administration, using a light-blocking corneal shield and copious saline flushing to prevent inadvertent exposure of the eye to light and photoconverter gel. While controlled evaluations of the periocular/eyelid microbiome and the impact of intertriginous microenvironments on periocular microbial populations are lacking, we considered the pathogens isolated from this case to be relevant based on expert opinion.FBM monotherapy did improve the clinical appearance and bacterial density of affected skin temporarily, suggesting that uncontrolled concurrent factors such as the altered intertriginous microenvironment, eyelid disease and epiphora prevented complete resolution. Periocular FBM may be more effective when concurrent factors are controlled. Additionally, treatment frequency was based on prior FBM studies yet it is possible that an altered frequency of application could improve response.

本报告还描述了一种安全可行的眼周FBM给药方案，使用遮光的角膜保护罩和大量的生理盐水冲洗，以防止眼睛不慎接触到光和光转换凝胶。虽然目前缺乏对眼周/眼睑微生物组的对照评估，以及皮褶微环境对眼周微生物群的影响，但我们根据专家意见认为从该病例分离出的病原体具有相关性。FBM单药治疗可暂时改善患病皮肤的临床外观和细菌密度，提示未受控制的并发因素如皮褶微环境的改变、眼睑疾病和泪溢阻碍了其完全缓解。当合并因素得到控制时，眼周FBM可能更有效。此外，治疗频率是基于之前的FBM研究，但改变治疗频率有可能提高疗效。

 

By establishing a protocol for periocular FBM administration, this report facilitates future studies. Applicability could extend to periocular bacterial dermatitis associated with other conditions, offering an option for patients with multidrug-resistant infections. Additionally, as FBM has wound-healing effects, it could be assessed as an adjunct to accelerate healing of periocular wounds or surgical incisions.

通过建立眼周FBM给药方案，该报告为未来的研究提供了便利。适用范围可扩展至与其他疾病相关的眼周细菌性皮炎，为多重耐药感染患犬提供一种选择。此外，由于FBM具有伤口愈合作用，因此可以评估其作为加速眼周伤口或手术切口愈合的辅助手段。

 

In conclusion, this report describes the successful application of rhytidectomy to treat EFF-HB-associated periocular dermatitis and a protocol for the safe application of periocular FBM in a dog. These techniques offer new therapeutic avenues for the management of canine periocular dermatoses.

综上所述，本报告描述了成功应用除皱术治疗EFF-HB相关眼周皮炎，以及在犬中安全应用眼周FBM的方案。这些技术为犬眼周皮肤病的治疗提供了新的治疗方案。

 

 

杨先生

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