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Successful management of feline pemphigus foliaceus with pentoxifylline and topical hydrocortisone aceponate
己酮可可碱和外用氢化可的松醋丙酯成功治疗猫落叶型天疱疮
作者：Stefan Hobi Julia A. Beatty Jeanine R. Sandy Vanessa R. Barrs
Abstract
摘要
The treatment regimen for feline pemphigus foliaceus (PF), an autoimmune disease caused by auto-antibodies against proteins of the desmosome junction, usually includes high doses of oral or parenteral immunosuppressive drugs, typically glucocorticoids. This case adds to a growing body of evidence that topical hydrocortisone aceponate is effective for the treatment of feline PF, and demonstrates the practical use of a non-invasive diagnostic method for histopathology when owners refuse a biopsy to support a clinical diagnosis of PF. Finally, this case highlights an international trend of owner-initiated treatment of feline infectious peritonitis (FIP) using unlicensed, unregistered drugs.
猫落叶型天疱疮(PF)是一种由抗桥粒连接蛋白自体抗体引起的自体免疫性疾病，治疗方案通常包括大剂量口服或肠外免疫抑制药物，典型的是糖皮质激素。本病例进一步证明了外用氢化可的松醋丙酯治疗猫PF是有效的，并证明了当宠主拒绝活检以支持临床诊断PF时，一种非侵入性组织病理学诊断方法的实际应用。最后，本病例强调了一个国际趋势，即使用未经许可、未注册的药物治疗猫传染性腹膜炎(FIP)。
KEYWORDS
关键词
autoimmune disease, dermatology, feline, pemphigus, skin, treatment
自体免疫性疾病、皮肤病、猫、天疱疮、皮肤、治疗
1 INTRODUCTION
1 介绍
Pemphigus foliaceus (PF), although rare in most species, is the most commonly reported autoimmune disease in cats. Most affected cats are middle-aged (5–8 years) with no clear breed or gender predisposition and typically present with yellow to brown, adherent crusting skin lesions involving the concave and convex surfaces of the pinnae, dorsal nose, claw folds and circumferentially around the nipples. Pruritus can be variable. Systemic signs are typically mild and non-specific. These may include fever, lethargy and anorexia. A definitive diagnosis of feline PF requires histological documentation of epidermal and/or mural follicular pustules containing numerous acantholytic keratinocytes and non-degenerate neutrophils. In addition, there should be compatible clinical signs. Other causes for crusting and acantholysis, including pyoderma and dermatophytosis, should also be ruled out. Although indirect immunofluorescence to detect IgG anti-keratinocyte autoantibodies would be ideal to confirm a diagnosis of feline PF, the diagnostic criteria described above are considered adequate. The prognosis is considered good but most cats with PF require long-term immunosuppressive treatment (i.e., oral glucocorticoids, ciclosporin, chlorambucil, gold salts, etc.). It’s important to inform clients about the high relapse risk, either spontaneously or during treatment adjustments. The time until disease control can vary but is on average 3 weeks. In human medicine, drugassociated PF is subdivided into drug-triggered and drug-induced PF. In the latter, there is a good chance of stopping medication without disease relapse after initial treatment and cessation of the offending drug. The former typically needs longterm treatment similar to spontaneous cases of PF. There is evidence that the same classification for PF can be applied to companion animals. Various triggers reported in cats include drugs (doxycycline, itraconazole, lime sulphur, others), vaccination, neoplasia (thymoma) and infectious diseases (leishmaniosis).
落叶型天疱疮(PF)，虽然在大多数物种中罕见，但是猫中最常见的自体免疫性疾病。大多数患猫年龄是中年(5-8岁)，没有明确的品种或性别倾向，通常表现为黄色到棕色，粘附性结痂性皮肤病变， 位于廓、鼻背、甲褶和乳头周围。瘙痒多样化。全身症状通常是轻微和非特异性的。这些症状可能包括发烧、嗜睡和厌食症。猫PF的确诊是组织病理学显示表皮层和/或毛囊壁脓疱含有大量棘层松懈角质形成细胞和非退行性中性粒细胞。此外，还应具有相容的临床症状。应排除其他导致结痂和棘层松懈的病因，包括脓皮病和皮肤癣菌病。虽然间接免疫荧光检测抗角质形成细胞自体抗体IgG是确诊猫PF的理想方法，但上述诊断标准被认为是足够的。预后被认为是良好的，但大多数PF患猫需要长期的免疫抑制治疗(即口服糖皮质激素、环孢素、氯霉素、金盐等)。重要的是要告知客户高复发风险，无论是自发的还是在治疗调整期间。疾病控制之前的时间可能有所不同，但平均为3周。在人类医学中，药物相关性PF又分为药物触发性（trigger）PF和药物诱发性（induce）PF，后者在初始治疗和停止违规药物后，有很大机会停止用药而不复发。前者通常需要长期治疗，类似于自发性PF病例。有证据表明，PF的相同分类也适用于伴侣动物。据报道，猫的各种诱因包括药物(多西环素、伊曲康唑、石硫合剂、其他等)、疫苗接种、肿瘤(胸腺瘤)和传染病(利什曼病)。
Here we describe a successful therapeutic approach to PF in a cat with severe co-morbid disease, in which the administration of immunosuppressive doses of systemic glucocorticoids was considered contraindicated. A non-invasive technique to support our diagnosis was used, which may be useful when full thickness biopsies are not possible.
本文描述了一例因患有严重共病而使用免疫抑制剂量的全身性糖皮质激素禁忌的猫PF的成功治疗方法。我们使用了一种非侵入性技术来支持我们的诊断，当不可能进行全层活检时，这可能是有用的。
2 CASE DESCRIPTION
2 病例描述
A 2-year old female spayed domestic short-haired cat with a 2-month history of non-resolving skin lesions was presented to the dermatology unit of City University Veterinary Medical Centre, Hong Kong. She had been regularly dewormed, vaccinated, had no travel history and spent the majority of time indoors. Neither the owner nor the other cat in the household had pruritus or skin lesions.
一只2岁已绝育雌性家养短毛猫，因2个月未痊愈皮肤病变病史，就诊于香港城市大学兽医医学中心皮肤科。她定期驱虫、接种疫苗，没有旅行史，大部分时间都在室内。宠主和家里的另一只猫都没有瘙痒或皮肤病变。
Three months before referral, a presumptive diagnosis of non-effusive feline infectious peritonitis (FIP) had been made. This was based on consistent clinicopathological findings including fever, weight loss, anorexia and vomiting, mild non-regenerative anaemia (HCT: 30.2 %, normal range: 30.3–52.3 %; reticulocytes: 19 K/µl, normal range: 3–50 K/µl), hyperglobulinaemia (7.3 g/dl, normal range: 2.8–5.1 g/dl), low range albumin (2.5 g/dl, normal range: 2.3–3.9 g/dl) and decreased albumin/globulin ratio (0.3, normal range: 0.5–1.2). In addition, diagnostic imaging findings included severe enlargement of the mesenteric lymph nodes (3 cm length, median length: 0.8 cm), thickening of the small intestinal muscularis mucosae, and a heterogeneous “mottled” spleen. The presence of pyogranulomatous inflammation with no detectable microorganisms in modified Wright Giemsa stained cytological preparations of fine-needle aspirate organ biopsies of the small intestine, spleen and enlarged lymph nodes supported a presumptive diagnosis of FIP. There were no skin abnormalities at this time. Independent of veterinary advice, the owner initiated treatment with a 12-week course of daily subcutaneous injections of an unregistered drug believed to be a nucleoside analogue antiviral (described to be GS441524) and not approved for veterinary use. One week after the presumptive diagnosis of FIP was made, and before commencement of the course of injectable antiviral medication, the cat developed crusting skin lesions on the nose and paws. These skin lesions were empirically treated by another veterinarian with itraconazole (4.8 mg/kg q24 h PO: Itracin®; Europharm Lab Co. Ltd., Hong Kong, China), amoxicillin/clavulanic acid (14.5 mg/kg q12 h PO; Amoxyclav®; AlfaMedic Ltd., Hong Kong, China), daily topical antiseptic solution containing chlorhexidine gluconate (HiBiSCRUB®; Regent Medical Overseas Ltd., Manchester, United Kingdom) and twice weekly topical lime sulphur (Lime Sulfur Dip®; Vetoquinol S.A., Lure, France). Ten days later, due to the lack of clinical response the cat was referred to a board-certified dermatologist for further assessment.
在转诊前三个月，假定诊断为非渗出性猫传染性腹膜炎(FIP)。这是基于一致的临床病理结果，包括发热、体重减轻、厌食和呕吐、轻度非再生性贫血(HCT: 30.2%，正常范围:30.3 - 52.3%;网状细胞:19 K/µl，正常范围:3-50 K/µl)，高球蛋白血症(7.3 g/dl，正常范围:2.8-5.1 g/dl)，低白蛋白(2.5 g/dl，正常范围:2.3-3.9 g/dl)和白蛋白/球蛋白比值降低(0.3，正常范围:0.5-1.2)。此外，影像学检查结果包括肠系膜淋巴结严重肿大(长度3cm，中位长度0.8 cm)，小肠粘膜肌层增厚，脾脏呈异质性“斑驳”。在改良的Wright Giemsa染色的小肠、脾脏和肿大的淋巴结细针穿刺器官活检的细胞学检查结果为，无微生物的脓肉芽肿性炎症，支持FIP的推定诊断。在这个时候没有皮肤异常。在没有兽医建议的情况下，宠主开始了12周的疗程，每天皮下注射一种未注册的药物，据信是一种核苷类似物抗病毒药物(描述为GS441524)，未获批准用于兽医。在做出FIP推定诊断一周后，在开始注射抗病毒药物之前，猫的鼻部和爪部出现了结痂性皮肤病变。这些皮肤病变由另一位兽医给予伊曲康唑(4.8 mg/kg q24 h PO:)，阿莫西林/克拉维酸(14.5 mg/kg q12 h PO)，每日外用含有氯己定葡萄糖酸盐抗菌香波和每周两次外用石硫合剂。十天后，由于无临床效果，这只猫被转诊给一位经过认证的皮肤科医生进行进一步评估。
On physical examination at referral, all vital signs were within normal limits. The cat’s body weight was 3.45 kg and the body condition score was 3/9, indicating the cat was underweight. Mild, multfocal erythema and crusting were present on the dorsal nose, concave pinnae and the dorsal, interdigital, haired skin and claw folds of all four paws. Some of the digits were swollen and the cat resented palpation of the digits (Figure 1). Two sharply demarcated, 2 cm large areas of complete focal alopecia with central raised adherent crusts were on the shoulder and mid-dorsum, in areas of previous antiviral subcutaneous injections. Pruritus was moderate to severe and mainly focused on the affected areas including the aforementioned alopecic locations. Cytological preparations of crusts from the pinnae and affected digits revealed non-degenerate neutrophils, nuclear streaming and several clusters of acantholytic keratinocytes with an absence of bacterial and fungal organisms. Other dermatological investigations such as skin scraping, trichogram and Wood’s lamp examination, from various affected skin areas, were unremarkable. Major differential diagnoses considered were infectious causes (bacterial or fungal organisms, esp. Trichophyton spp.), autoimmune causes (PF), cutaneous adverse drug reactions and FIP-associated dermatitis. Fullthickness skin biopsies were recommended, but the owner declined because of concerns about sedation and anaesthesia. Instead, multiple crusts from the pinnae and paws were sampled and submitted for histopathology. In addition, dermatophyte culture of hair and crusts as well as an aerobic bacterial culture of surface swabs from the lesions on the paws were performed. A blood test for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) antigen (IDEXX SNAP Combo) was negative. Amoxicillin/clavulanic acid (14.6 mg/kg q12 h PO; Clavulox®; Zoetis, Rhodes, Australia) was continued pending the results of the bacterial culture and all topical therapy was discontinued. The antiviral injections were continued by the owner. Three weeks after referral, skin lesions had not improved and new crusting lesions were identified on the dorsum and around the nipples. Cytology from the crusts at the new lesion sites revealed neutrophilic inflammation, clusters of acantholytic keratinocytes and no microorganisms. Cytology of the two focal areas of alopecia was unremarkable. Results from the previous tests included a negative dermatophyte culture and light growth of Staphylococcus aureus susceptible to amoxicillin/clavulanic acid. Histopathology revealed multiple large intracorneal crusts composed of abundant intact neutrophils, rounded/angular acantholytic keratinocytes and focal colonies of bacterial cocci at areas of erosions (Figure 2). A Periodic Acid-Schiff (PAS) stain did not reveal any fungal organisms. A diagnosis of PF was made based on the appearance and distribution of the lesions, supportive histopathology, a negative fungal culture and the lack of response to an antimicrobial to which the cultured S. aureus was susceptible. Due to the presumptive FIP diagnosis, immunosuppressive doses of systemic glucocorticoids were avoided and therapy was initiated using topical hydrocortisone aceponate twice daily (one pump per application, applied indirectly via product-moistened cotton swab) on affected areas (Cortavance®; Virbac Limited, Sufflox, United Kingdom), pentoxifylline (26.5 mg/kg q12 h PO; Pentoxifylline 400mg®; Oceanside Pharmaceuticals, New Jersey, USA) and omega-3/6-fatty acids (767 mg q24 h PO; VetriScience®; VetriScience Laboratories; Vermont, USA). At re-examination 2 weeks later, the skin lesions improved significantly. The cat no longer resented its paws being touched and only a few crusts remained on the front paws and the trunk. The cat was more active and no signs of iatrogenic Cushing’s occurred. The owner reported that if the hydrocortisone aceponate application was missed, the crusts immediately relapsed. Cytology of the residual crusts revealed neutrophilic inflammation, no microorganisms and no acantholytic keratinocytes. Pruritus was still present and cetirizine (0.7 mg/kg q12 h PO; Zyrtec®; GlaxoSmithKline, Hong Kong, China) was added (Griffin et al., 2012). Two months later, clinical examination revealed a healthy cat, free of systemic signs with complete resolution of crusted skin lesions and pruritus. The 12- week injection course of the antiviral drug had been completed by the owner during this time. The two well-demarcated areas of alopecia remained. The topical glucocorticoid was tapered and completely withdrawn after approximately 6 months. The pentoxifylline was subsequently reduced to once daily and withdrawn 4 months later. At the time of writing, 20 months have passed since the initial presentation and 10 months since all medications were discontinued and the cat is clinically normal except for mild gingivostomatitis, with no systemic signs and no relapse of the crusting skin lesions (Figure 3). On repeating serum biochemistry, the only residual abnormality was a mild persistent hyperglobulinaemia (5.6 g/dl, normal range: 2.8–5.1 g/dl). The total serum protein (8.7 g/dl, normal range: 5.7–8.9 g/dl), albumin (3.1 g/dl, normal range: 2.2–4.0 g/dl) and the albumin/globulin ratio had resolved (0.5, normal range: 0.5–1.2). The two alopecic areas persisted.
经转诊体检，所有体格检查均在正常范围内。患猫体重为3.45 kg，体况评分为3/9，体重偏轻。在鼻背侧、耳廓凹面和所有四爪背侧、指间、有毛皮肤和甲褶出现轻微的多灶性皮肤发红和结痂。部分手指肿胀，猫不喜欢触诊指部(图1)。肩部和背部中部有两个边界明显的2厘米大的局灶性完全脱毛区，中心有隆起的结痂覆盖，是之前注射过抗病毒药物的区域。瘙痒中度至重度，主要集中在患病区域，包括前面提到的脱毛部位。从耳廓和患病指的结痂的细胞学检查显示非退行性中性粒细胞、染色质和几簇棘层松懈的角质形成细胞，没有细菌和真菌微生物。从各个患病皮肤区域进行的其他皮肤病学检查，如皮肤刮片、毛发检查和伍德灯检查，未见明显异常。主要的鉴别诊断包括感染性病因(细菌或真菌微生物，特别是毛癣菌)、自体免疫性病因(PF)、皮肤药物不良反应和FIP相关皮肤病。建议进行全层皮肤活检采样，但由于宠主担心镇静和麻醉拒绝了。取而代之的是，从耳廓和爪部上取多处结痂并进行组织病理学检查。此外，对毛发和结痂进行皮肤真菌培养，对爪部病变表面棉签采样进行需氧细菌培养。猫免疫缺陷病毒(FIV)和猫白血病病毒(FeLV)抗原的血液测试呈阴性。等待细菌培养结果期间，继续使用阿莫西林/克拉维酸(14.6 mg/kg q12 h PO)治疗，并停止所有外部治疗。宠主继续给猫注射抗病毒药物。转诊三周后，皮肤病变没有改善，在背部和乳头周围发现了新的结痂病变。新病变部位结痂的细胞学检查显示中性粒细胞性炎症，成簇的棘层松懈的角质形成细胞，无微生物。两个局灶脱毛区域的细胞学检查结果均未见异常。以前的检测结果包括皮肤菌培养阴性，金黄色葡萄球菌轻度增殖，且对阿莫西林/克拉维酸敏感。组织病理学显示，多个大的角质层内结痂，含大量完整的中性粒细胞、圆形/角状棘层松懈的角质形成细胞和糜烂区域的球菌局灶定植(图2)。周期性酸-希夫(PAS)染色未发现任何真菌微生物。根据病变的外观和分布、支持性组织病理学、真菌培养阴性和对培养的金黄色葡萄球菌易感的抗菌药物缺乏治疗效果，诊断为PF。由于疑似诊断FIP，避免使用免疫抑制剂量的全身性糖皮质激素，并开始使用外用氢化可的松醋丙酯(皮乐美)，每天两次(每次应用一泵，将产品浸湿棉棒间接应用)对患病区域进行治疗，服用己酮可可碱(26.5 mg/kg q12 h PO)和omega-3/6-脂肪酸(767 mg q24 h PO)。2周后复查，皮肤病变明显好转。这只猫不再讨厌触诊爪部，前爪和躯干上仅剩少量结痂。猫更活跃，没有医源性库欣的症状发生。宠主报告说，如果不使用氢化可的松醋丙酯，结痂就会立即复发。剩余结痂的细胞学检查显示中性粒细胞性炎症，无微生物和棘层松懈角质形成细胞。瘙痒仍然存在，服用西替利嗪(0.7 mg/kg q12 h PO)。两个月后，临床检查发现猫健康，没有全身症状，结痂性皮肤病变和瘙痒症完全消失。期间宠主已完成12周的抗病毒药物注射疗程。那两个边界清晰的脱毛区还在。外用糖皮质激素逐渐减量，大约6个月后完全停用。己酮可可碱随后减少到每天一次，4个月后停用。在撰写本文时，距离首次出现症状已经过去了20个月，距离停止所有药物治疗已经过去了10个月，除了轻度牙龈炎外，猫临床正常，没有全身症状，也没有结痂性皮肤病变复发(图3)。在复查血清生化测试中，唯一残留的异常是轻度持续性高球蛋白血症(5.6 g/dl，正常范围:2.8-5.1 g/dl)。血清总蛋白(8.7 g/dl，正常范围:5.7-8.9 g/dl)、白蛋白(3.1 g/dl，正常范围:2.2-4.0 g/dl)和白蛋白/球蛋白比(0.5，正常范围:0.5 - 1.2)均已消退。这两个脱毛区域持续存在。
3 DISCUSSION
3 讨论
The diagnosis of non-effusive FIP can be challenging, since the most common confirmatory testing used by veterinarians in clinical practice is quantitative reverse transcriptase polymerase chain reaction (RT-PCR) detection of FCoV RNA in effusions, which was not possible in this case. Quantitative-PCR of RNA extracts from the organ fine-needle aspirates of this case, may have facilitated a definitive diagnosis, although a negative test result would not rule out FIP due to the low sensitivity of this technique.
非渗出性FIP的诊断可能具有挑战性，因为兽医在临床实践中使用的最常见的验证性检测是在积液中定量逆转录酶聚合酶链反应(RT-PCR)检测FCoV RNA，这在本病例中是不可能进行的。从该病例的细针抽吸物中定量PCR检测提取RNA，可能有助于明确诊断，但由于该技术的低敏感性，阴性检测结果不能排除FIP。
The clinicopathological findings of systemic disease including the fever and diagnostic imaging findings resolved in this case after treatment with the antiviral injections suspected to be the nucleoside analogue GS441524. A recent study demonstrated high efficacy of an unregistered oral multi-component drug containing GS441524 in curing naturally-occurring FIP. However, the clinical presentation described in the cat in this report could have been caused by other infections (e.g. other viral, toxoplasmosis, atypical bacterial), neoplastic (e.g. lymphoma) or inflammatory diseases, and the compound(s) in the injections administered by the owner could not be confirmed.
本病例在接受怀疑为核苷类似物GS441524的抗病毒注射治疗后，全身性疾病的临床病理表现(包括发热和影像学诊断结果)得到缓解。最近的一项研究表明，一种未注册的含GS441524的口服多成分药物在治疗自发性FIP方面具有很高的疗效。然而，本报告中描述的猫的临床表现可能是由其他感染(如其他病毒、弓形虫病、非典型细菌)、肿瘤(如淋巴瘤)或炎性疾病引起的，而宠主注射的化合物无法确认。
The diagnosis of PF in this cat with presumptive concurrent non-effusive FIP prompted a treatment approach without the use of traditional immunosuppressive drugs that could result in an adverse outcome. We elected to use topical administration of a hydrocortisone aceponate spray, which has been described previously in two cases of feline PF. This drug formulation is licenced for the treatment of inflammatory and pruritic dermatoses as well as atopic dermatitis in dogs. Use in cats is off-label, although, previous studies support its safety and efficacy.
这只猫被诊断为PF，并推测并发无渗出性FIP，这促使治疗方法不使用可能导致不良结果的传统免疫抑制药物。我们选择外用氢化可的松醋丙酯喷雾剂，该喷雾剂已在两例猫PF病例中被描述。该药物已获许可用于治疗犬的炎性和瘙痒性皮肤病以及特应性皮炎。虽然之前的研究支持它在猫上的安全性和有效性，但在猫上的使用是标签外使用。
In addition, in order to avoid significant suppression of the Th1 immunity by conventional therapy and because of its efficacy in treatment of human pemphigus vulgaris, pentoxifylline was added. Although not efficacious against FIP, it is known to be well tolerated in cats with FIP.
此外，为了避免传统治疗对Th1免疫功能的显著抑制，并考虑到己酮可可碱对人寻常型天疱疮的治疗效果，添加了己酮可可碱。虽然对FIP无效，但已知它对患有FIP的猫具有良好的耐受性。
In human medicine, pentoxifylline has been used as an adjuvant medication for the treatment of pemphigus vulgaris since it has been shown to inhibit TNF-alpha, playing a partial role in the pathogenesis of the disease. Further studies are needed to evaluate the role of this cytokine in the pathogenesis of feline and canine PF as well as the potential role of pentoxifylline as an effective treatment alternative for this disease.
在人类医学中，己酮可可碱已被用作治疗寻常型天疱疮的辅助药物，因为它已被证明可以抑制TNF-α，在该病的发病机制中发挥部分作用。需要进一步的研究来评估该细胞因子在猫和犬PF发病机制中的作用，以及己酮可可碱作为一种有效治疗这种疾病的潜在作用。
Both itraconazole and lime sulphur are suspected initiators of PF in cats. However, as the skin lesions developed before both of these medications were administered and before the first injection of the antiviral drug, it is unlikely these drugs played a role. This was also supported by the calculated Naranjo score (Table 1), based on a questionnaire designed for the determination of a drug to be involved in an adverse event. Provocation, re-administration of the offending drug, was however not considered due to the possibility of an even more serious reaction. An association with vaccination or a deworming product was considered less likely given the long-time interval of several months in between the application of these products and the development of PF.
伊曲康唑和石硫合剂都被怀疑是猫PF的启动因素。然而，由于皮肤病变是在使用这两种药物和第一次注射抗病毒药物之前出现的，因此这些药物不太可能起作用。这也得到了Naranjo评分的支持(表1)，该评分基于一份旨在确定药物相关不良事件的问卷。然而，由于可能出现更严重的反应，因此不考虑再激发，重新给药。考虑到接种疫苗或驱虫产品与PF发生之间有几个月的长时间间隔，因此认为不太可能与疫苗或驱虫产品有关。
Viral infections such as COVID-19, Epstein–Barr virus, human endogenous retroviruses, herpesvirus (human and equine) and canine parvovirus are reported to trigger autoimmune diseases. In addition, FCoV has been directly implicated to cause cutaneous papular to nodular lesions in cats with FIP, characterised histologically by granulomatous inflammation and necrosis. FCoV can be detected in the cytoplasm of macrophages within the dermis in affected skin, using immunohistochemistry. The gross appearance, distribution of skin lesions and histopathological findings in our case were not consistent with FIP-associated dermatitis. There is increased evidence of a potential association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans and the rapid development of autoimmune and/or autoimmune dysregulation. Several reaction patterns such as cutaneous rashes, vasculitis, autoimmune cytopenia, antiphospholipid syndrome, central and peripheral neuropathy, myositis, myocarditis, Guillain–Barré syndrome, Miller Fisher Syndrome and Kawasaki like disease haven been described. However, since FIP is common and concurrent PF has not previously been reported, such a mechanism is unlikely, yet still possible.
据报道，COVID-19、EB病毒、人内源性逆转录病毒、疱疹病毒(人和马)和犬细小病毒等病毒感染可引发自体免疫性疾病。此外，FCoV直接导致FIP猫的皮肤丘疹到结节性病变，组织学上表现为肉芽肿性炎症和坏死。应用免疫组织化学方法，可在患病皮肤真皮层巨噬细胞的细胞质中检测到FCoV。我们病例的整体表现、皮肤病变分布和组织病理学结果与FIP相关皮肤病不一致。越来越多的证据表明，人类严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染与自体免疫和/或自体免疫失调的快速发展之间存在潜在关联。几种反应模式如皮疹、血管炎、自体免疫性细胞减少、抗磷脂综合征、中枢和周围神经病变、肌炎、心肌炎、Guillain-Barré综合征、Miller Fisher综合征和川崎样病已被描述。然而，由于FIP是常见的，并发PF以前没有报道，这样的机制是不太可能的，但仍然是可能的。
Overall, a spontaneous form of PF is highly unlikely and the final causative trigger is unclear in this case.
总的来说，不太可能是自发性的PF形式，在这个病例中，最终的诱因尚不清楚。
The focal temporarily crusted and alopecic lesions which were persistent and non-responsive to therapy were considered a sequela of the owner-administered injections since they correlated with the injection sites and this is a well-known phenomenon in veterinary dermatology. Severe irritation and focal areas of necrosis have been reported subsequent to subcutaneous injections of nucleoside analogues such as remdesivir and GS441524 in cats. In addition, the owner had not administered any topical spot-on products.
局部暂时性结痂和脱毛病变持续且对治疗无反应，被认为是宠主注射的后遗症，因为它们与注射部位相关，这是兽医皮肤病学中一个众所周知的现象。据报道，猫皮下注射核苷类似物(如瑞德西韦和GS441524)后，会出现严重刺激和局部坏死。此外，该宠主没有使用任何外用滴剂产品。
This case also highlights the challenges veterinarians currently face due to a growing widespread practice in Hong Kong and other regions of the use of unregistered, unlicensed drugs that claim to be nucleoside analogues, by owners desperate for a cure of an otherwise fatal disease of their pet.
这一案例也凸显了兽医目前面临的挑战，因为在香港和其他地区，宠物主人迫切希望治愈宠物的致命疾病，使用未经注册、未经许可、声称是核苷类似物的药物的做法越来越普遍。
Finally, this report also demonstrates that performing histopathology on crusts obtained from representative skin lesions can support a diagnosis of PF when collection of full-thickness skin biopsies is not possible. Nevertheless, further studies are needed to evaluate the diagnostic utility of this described technique. Other non-invasive techniques to support a diagnosis include cytological examination of fineneedle aspirate contents of intact pustules. However, such lesions may be absent when pruritus is present or the pustules rupture due to their thin and fragile nature. Care needs to be taken in interpreting cytological results, since Staphylococcus spp. and dermatophytes can cause PF-like lesions as described in humans and dogs and anecdotally in cats.
最后，本报告还表明，当无法采集全层皮肤活检时，对代表性皮肤病变的结痂进行组织病理学检查可以支持PF的诊断。然而，还需要进一步的研究来评估这种技术的诊断效用。其他支持诊断的非侵入性技术包括对完整脓疱细针抽吸物进行细胞学检查。然而，由于脓疱薄而易碎，当出现瘙痒或脓疱破裂时，这种病变可能不存在。在解释细胞学结果时需要谨慎，因为葡萄球菌和皮肤癣菌可以引起人和犬的PF样病变，在猫上也有传闻。
In summary, this report describes the first case of feline PF in China and an effective alternative treatment approach consisting of pentoxifylline and topical hydrocortisone aceponate in a patient with a history of a severe systemic infectious disease.
总之，本报告是中国首例报道的猫PF病例，同时患猫有一种严重全身性感染性疾病，使用己酮可可碱和外用氢化可的松醋丙酯，作为有效替代治疗方法。
FIGURE 1 (a) Clinical: initial presentation; hypotrichosis and multifocal crusts with paronychia of P1 and P2. (b) Caseous exudate in the claw folds in addition to paronychia and erosions. Also note the golden crusts involving the paw. (c) Clinical: initial presentation; adherent golden crusts, erosions and erythema on the inner pinnae (arrow). (d) Crusts and erythema on the planum nasale, philtrum and adjacent haired skin (arrow)
图1 (a)临床:初期表现;少毛症和多灶性结痂伴甲沟炎P1和P2。(b)除甲沟炎和糜烂外，爪褶有干酪样渗出物。还要注意爪上的金黄色结痂。(c)临床:初期表现;耳廓内侧有粘附的金黄色结痂、糜烂和皮肤发红(箭头)。(d)鼻平面、人中及邻近有毛皮肤上的结痂和发红(箭头)。
FIGURE 2 (a) Histopathology (H&E stain × 400 magnification); crust material with abundant neutrophils and scattered angular to rounded acantholytic keratinocytes (arrows). (b) Histopathology (H&E stain × 1000 magnification); crust material; high power to show rounding of acantholytic keratinocytes (arrows) surrounded by a sea of neutrophils
图2 (a)组织病理学(H&E染色× 400倍);结痂物质有丰富的中性粒细胞分散的包围着棘层松懈的角质形成细胞(箭头)。(b)组织病理学(H&E染色× 1000倍);结痂物质;高倍图显示海量中性粒细胞包围着棘层松懈的角质形成细胞(箭头)
FIGURE 3 (a), (b) Clinical appearance at the time of writing: current presentation; good general condition, no systemic signs and no pemphigus foliaceus lesions
图3 (a)， (b)撰写本文时的临床表现:当前表现;整体情况良好，无全身症状，无落叶型天疱疮病变。 | 
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发表于 2024-6-18 22:15:00
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