与外用植物性跳蚤预防剂相关的猫的无菌性中性粒细胞性...

王帆

Sterile neutrophilic dermatitis in a cat associated with atopical plant-derived oil flea preventative   

与外用植物性跳蚤预防剂相关的猫的无菌性中性粒细胞性皮炎

翻译：鲜琳

A 4-year-old, female spayed, domestic short hair cat presented with an acute eruption of pustules and bullous plaques after application of a plant-based, essential oil flea preventative. Histopathological evaluation of biopsies revealed severe neutrophilic infiltrate within the dermis and culture was negative. The cat’s skin lesions responded rapidly to glucocorticoid monotherapy.

1只4岁雌性已绝育的家养短毛猫在使用一种植物性精油跳蚤预防剂后，出现急性脓疱和大疱性斑块。活检组织病理学显示真皮内重度中性粒细胞浸润，培养结果为阴性。猫的皮肤病变对糖皮质激素治疗快速有效。

Introduction  

介绍

Sterile neutrophilic dermatoses are a group of rare diseases in humans characterised by neutrophilic dermal infiltration. Three well-described forms exist: Sweet’s syndrome, pyoderma gangrenosum and superficial amicrobial pustulosis.Similar cases are rare in animals and reported more generally as sterile neutrophilic dermatitis with comparisons to Sweet’s syndrome and pyoderma gangrenosum. Here, we describe sterile neutrophilic dermatitis in a cat that developed after application of a topical plant-based, essential oil flea preventative. There is only one previous report in a cat, for which a culture was not performed, and treatment included an antimicrobial.

无菌性中性粒细胞性皮肤病是一组以中性粒细胞浸润皮肤为特征的人类罕见疾病。存在三种良性描述形式：Sweet综合征、坏疽性脓皮病和浅表性无微生物性脓疱病。类似病例在动物中很少见，与Sweet综合征和坏疽性脓皮病相比，更多地报告为无菌性中性粒细胞皮炎。本文描述了一只猫在外用植物性精油跳蚤预防剂后发生的无菌性中性粒细胞皮炎。之前在猫中仅有一份报告，未对其进行培养，治疗包括一种抗生素。

Case report   

病例报道

A 4-year-old, female spayed, domestic short hair cat presented for acute fever, lethargy and skin lesions. Eight days previously, the owner applied an over-the-counter topical flea preventative (Pet Armor naturals, Sergeant’s Pet Care Products; Omaha, NE, USA) consisting of peppermint oil, clove oil, lemongrass oil, canola oil, vanillin and citric acid. Clinical signs and lesions started six days after application.

一只4岁雌性已绝育家养短毛猫因急性发热、嗜睡和皮肤病变就诊。8天前，主人使用过一种外用非处方跳蚤预防剂，包含薄荷油、丁香油、柠檬草油、菜籽油、香草醛和柠檬酸。给药后6天开始出现临床症状和病变。

Examination revealed multifocal ulcerations and crusts on the lips and pinna. There were many pustules, some coalescing to form larger bullous plaque-like lesions, leading to ulcerations on the ventral abdomen extending into the thoracic region and medial thighs (Figure 1a). The area of application (dorsal neck) was unaffected. These lesions appeared painful. Paronychia was present on all four paws. The cat was lethargic and pyrexic (104°F). Significant laboratory abnormalities included a mild left shift and bilirubinaemia (see Supporting information,Table S1).

检查发现唇部和耳廓有多灶性溃疡和结痂。脓疱较多，部分融合形成较大的大疱性斑块样病变，腹侧腹部溃疡延伸至胸部及大腿内侧（图1a）。给药区域（颈背部）未患病。这些病变表现为疼痛。4只爪均出现甲沟炎。该猫嗜睡和发热(104°F)。实验室显著异常包括轻度核左移和胆红素血症（见支持信息，表S1）。

Thoracic radiographs and abdominal ultrasound were unremarkable. Cytological findings from lesions on the ventrum, nailbed and pinna were similar: neutrophilic inflammation without bacteria or acantholytic cells. Deep skin scrapings revealed no ectoparasites. Aerobic bacterial culture from a pustule revealed no growth.

胸部x线片及腹部b超无异常。腹侧、甲床和耳廓病变的细胞学结果相似：中性粒细胞炎症反应，无细菌或棘层松解细胞。皮肤深刮未见体外寄生虫。一个脓疱进行需氧菌培养显示无菌落生长。

Under sedation, three punch biopsies were collected from the ventral abdomen. On histopathological examination, there was a neutrophilic dermatitis ranging from mild interstitial and dense perifollicular infiltrates of neutrophils to formation of large pools of neutrophils resembling abscesses. Neutrophils also infiltrated follicular epithelium and multifocally formed small pustules. In addition, there was moderate-to-severe oedema and, in more severely affected specimens, mild scattered haemorrhage. No ulceration, infectious agents or acantholytic cells were observed. A Luna stain was performed to confirm that the infiltrating granulocytes were not eosinophils (Figure 2). Immunohistochemical investigation for calicivirus detected no antigen.

在镇静情况下，从腹部腹侧采集3份打孔活检样本。在组织病理学检查中，存在中性粒细胞性皮炎，范围从中性粒细胞的真皮间质轻度浸润和毛囊周致密浸润至形成类似脓肿的大中性粒细胞区。中性粒细胞也浸润毛囊上皮细胞，多灶性形成小脓疱。此外，存在中度至重度水肿，在受影响更严重的样本中，存在轻度散在性出血。未观察到溃疡、感染性微生物或棘层松解细胞。进行Luna染色以确定浸润的粒细胞不是嗜酸性粒细胞（图2）。杯状病毒的免疫组化未检测到抗原。

While histopathological results were pending, an autoimmune disease was suspected based on clinical features and cytological findings. During hospitalization,the cat was started on dexamethasone, 0.28 mg/kg,intravenously once daily. By the next morning, skin lesions were improved, and the fever had resolved (Figure 1b). The cat was more active and no longer appeared to be in pain. A bath with an oatmeal shampoo (DermAllay, Dechra; Overland Park, KS, USA) was performed as a result of the possible topical reaction. The cat was discharged on prednisolone, 0.94 mg/kg orally twice daily. A diagnosis of sterile neutrophilic dermatitis was made based on the combination of clinical features, histopathological results, negative culture and response to corticosteroids.

虽然组织病理学结果有待确定，但根据临床特征和细胞学结果怀疑自体免疫性疾病。住院期间，猫开始接受地塞米松，0.28 mg/kg，静脉注射，每日一次。次日早晨皮肤病变好转，发热已消退（图1b）。患猫有活力，似乎不再疼痛。由于可能的外用药反应，使用燕麦香波洗澡。猫出院后口服泼尼松龙0.94 mg/kg，每日两次。根据临床特征、组织病理学结果、培养阴性及对皮质类固醇的反应，诊断为无菌性中性粒细胞皮炎。

At recheck, 11 days after discharge, skin lesions had mostly resolved (Figure 1c). The cat had no skin lesions 54 days after discharge. Prednisolone was eventually tapered and discontinued, without new lesions appearing(follow-up of 237 days).

出院后11天复查，皮肤病变大部分消退（图1c）。该猫出院后54天无皮肤病变。泼尼松龙最终逐渐减量并停药，未出现新病灶（随访237天）。

Figure 1. Skin lesions on the ventrum of a cat with a sterile neutrophilic dermatitis.

(a) Pustules and bullous plaque-like lesions were present upon presentation of the case. (b) Decreased erythema and size of lesions was noted one day after initiation of therapy. (c) Eleven days after discharge from the hospital, only residual erythema, scaling and postinflammatory hyperpigmentation remained.

图1：一只患有无菌性中性粒细胞性皮炎的猫腹侧皮肤病变。

(a)病例出现脓疱和大疱性斑块样病变。(b)开始治疗后1天观察到红斑和病变尺寸减小。(c)出院后11天，仅残留红斑、皮屑和炎症后色素沉着。

Discussion  

讨论

This report describes a neutrophilic dermatitis in a cat that, based on lack of bacterial growth on culture and rapid response to steroids without a systemic antimicrobial, supports a sterile process. While the exact cause cannot be determined definitively, the topical flea prevention was a suspected trigger because clinical signs had started shortly (six days) after application. Once lesions had resolved they did not recur, which further suggests an association. Adverse events associated with plant essential oils have been reported, particularly agitation and hypersalivation in cats, yet a similar cutaneous reaction has not been described previously.

本报告描述了一只猫的中性粒细胞皮炎，基于培养物中无细菌生长和对无全身性抗菌剂的类固醇的快速反应，支持无菌过程。虽然无法明确确切原因，但由于给药后不久（6天）开始出现临床体征，因此怀疑局部跳蚤预防为诱因。一旦病变消退，没有复发，这进一步表明存在相关性。已经报告了与植物精油相关的不良事件，尤其是猫躁动和流涎，然而之前尚未描述过类似的皮肤反应。

The predominant bullous plaque lesions were unusual for a neutrophilic dermatitis. A case reported previously had primarily necrotic and ulcerative lesions,although the lesions noted in our case may represent a different stage of disease progression. Similar lesions have not been noted in dogs with neutrophilic dermatitis. Instead, common clinical manifestations include generalised erythroderma, macules, papules, wheals and ulcerations. Pustular and bullous lesions are more typical of pemphigus foliaceus, which was a major differential for our case and can be drug-induced. Paronychia and crusts, as noted in our case, also can present with pemphigus foliaceus.However, no acantholytic cells were present on cytological or histopathological evaluation, and there was no recurrence after the glucocorticoid was discontinued,making pemphigus foliaceus unlikely. These lesions are thought to have been late-stage changes of the pustular and bullous lesions. The fever and predominantly neutrophilic infiltrate in the superficial and mid-dermis share similarities to Sweet’s syndrome in humans. However,large abscess-like accumulations of neutrophils are more comparable to pyoderma gangrenosum in dogs.

显著的大疱性斑块病变不常见于中性粒细胞性皮炎。之前报告的1例病例主要有坏死性和溃疡性病变，但在我们的病例中观察到的病变可能代表疾病进展的不同阶段。在犬的中性粒细胞皮炎中未观察到类似病变。相反，常见的临床表现包括全身性红斑、斑点、丘疹、风疹和溃疡。脓疱和大疱病变更提示落叶型天疱疮，这是我们病例的主要鉴别诊断，可以是药物诱导。甲沟炎和结痂，如本病例所述，也可表现为落叶型天疱疮。但细胞学或组织病理学评价不存在棘层松解细胞，停用糖皮质激素后无复发，不像落叶型天疱疮。这些病变被认为是脓疱和大疱病变的晚期变化。发热和主要为真皮浅层和中层中性粒细胞浸润与人类Sweet综合征相似。然而，中性粒细胞的大脓肿样蓄积更像犬坏疽性脓皮病。

   

Overall, this report highlights a unique combination of clinical lesions with a putative topical compound as the trigger. Sterile neutrophilic dermatoses – other than pemphigus foliaceus – are rare in cats.

总之，本报告强调了一种独特的临床病变组合，推测外用化学成分为诱因。不同于落叶型天疱疮，无菌性中性粒细胞皮肤病在猫中罕见。

     

     

Figure 2. Photomicrographs of skin biopsy samples acquired from the ventral abdomen of a cat with sterile neutrophilic dermatitis.

(a) In some regions, large numbers of neutrophils infiltrated the interstitium of superficial to mid-dermis and tracked around follicles. Haematoxylin & eosin. (b) In other regions, the superficial dermis was expanded by oedema, and neutrophils formed dense pools resembling an abscess within the dermis. H&E. (c) Higher magnification of (a) showing infiltration of the follicular epithelium and formation of small pustules. H&E. (d) Higher magnification of (b) showing neutrophils mixed with mild to moderate haemorrhage and few histiocytes. H&E. (e) Luna-stained section demonstrating that the predominant granular leukocyte population was not stained, supporting that these are neutrophils. Only rare eosinophils were observed (arrow). (f) Higher magnification of (e).

图2：一只无菌性中性粒细胞皮炎患猫的腹部腹侧的皮肤活检采样显微照片。

(a)在一些区域，大量中性粒细胞浸润真皮浅层至中层的间质，并在毛囊周围可见。苏木精和伊红。(b)在其他区域，真皮浅层因水肿而扩张，中性粒细胞在真皮内形成类似脓肿的致密区。H&E.(c)(a)的高倍放大显示毛囊上皮细胞浸润和小脓疱形成。H&E.(d)(b)的高倍放大显示中性粒细胞混合轻度至中度出血和少量组织细胞。H&E.(E)Luna染色切片证明主要的白细胞群未被染色，支持这些是中性粒细胞。仅观察到罕见的嗜酸性粒细胞（箭头）。(f)(e)的高倍放大。

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