12 Clinical presentations in dogs
12 犬临床表现
12.1 Signalment
12.1临床表现
Malassezia dermatitis can potentially occur in dogs of any age, sex or breed, but signalment related predispositions have been reported. Malassezia dermatitis is often first diagnosed in dogs between one and three years of age, as might be expected in a disease that is frequently secondary to atopic dermatitis or due to genetic predisposition. Important breed predispositions are discussed in Section 7.1. There is no sex predisposition.
马拉色菌皮炎可能在任何年龄、性别、品种的犬中发生，但临床表现出有关易感性已被报道。马拉色菌皮炎通常在1-3岁之间被首次诊断出来，可能是经常继发于特应性皮炎或遗传易感性的疾病。重要的品种易感性将在7.1节中讨论，且没有性别倾向。
12.2 Historical features
12.2病史表现
Malassezia dermatitis typically presents as a pruritic dermatosis or otitis and it is a major differential diagnosis in any dog with those presenting signs. The severity of pruritus can vary, ranging from mild to very severe. In one report, the onset of clinical signs coincided with the summer or humid months and then persisted into winter, but this apparent seasonality has not been verified to be independent of an underlying seasonal allergy. The pruritus can manifest as face rubbing, head shaking, ear scratching, paw licking/chewing, anal scooting or generalized scratching, depending on the location of infection. A pruritic facial hyperaesthesia is occasionally seen in association with Malassezia cheilitis.
马拉色菌皮炎通常表现为瘙痒性皮肤病或耳炎，且任何具有此征的犬中都应作为主要鉴别诊断。瘙痒的严重程度可能会从轻度至重度有所不同。在一份报告中，临床症状的显现恰逢夏季或潮湿的月份然后持续至冬季，但尚未证明这种明显的季节性与潜在季节性过敏无关。根据感染部位的不同，瘙痒可表现为摩擦面部、摇头、抓耳、舔舐爪部/啃咬、磨蹭肛门或全身抓挠。偶尔会出现瘙痒性面部感觉过敏与马拉色菌唇炎有关。
12.3 Skin lesions and distribution
12.3皮肤病变和分布
The skin lesions in dogs with Malassezia dermatitis can be localised or generalised. Regional dermatitis commonly occurs on the muzzle, lips, ventral neck, axillae, ventral abdomen, medial hindlimbs, interdigital skin, perineum and in the external ear canal and intertriginous areas. Malassezia paronychia may occur in some cases. Some clinicians have observed anecdotally that a localized area of Malassezia overgrowth can occur following persistent licking. On examination, skin lesions are characterised by diffuse erythema and variable amounts of kerato-sebaceous scale that can be brown (Figure 4), yellow or grey in colour. The skin and hair coat may become greasy and self-induced alopecia can occur due to the pruritus. When paronychia is involved, there is red-dish-brown staining of the claws (Figure 5) or hair, with inflammation of the surrounding soft tissue. Chronic cases can have marked lichenification. Hyperpigmentation can also occur with chronicity, depending on the breed; for example, West Highland white terriers typically develop this change with chronic disease (Figure 6),whereas basset hounds typically do not. Dogs with generalised lesions often have an offensive, rancid odour.
犬马拉色菌皮炎的皮肤病变可以分为局部和全身性。局部病变常见于口鼻部、唇边、腹颈部、腋窝、腹侧部、后肢内侧、指间皮肤、会阴部、在外耳道和皮肤摩擦区域。在某些情况下，可能会出现马拉色菌甲沟炎。一些临床医生已注意到，经常舔舐导致局部区域的马拉色菌过度增殖。经检查皮肤病变特征：弥漫性红斑以及不同程度且可能为棕色、黄色或灰色角化皮脂性皮屑。皮肤和毛发可能变得油腻且由瘙痒引发自损性脱毛。当出现甲沟炎时爪部可能会出现红褐色或毛发（图5），伴周围软组织的发炎。慢性病例会出现明显的苔藓化病变。色素沉着也可以随着品种差异出现慢性病变；如西高地白㹴会因为慢性疾病的发生出现这种变化（图6），而巴吉度猎犬通常不会发生这种变化。犬一般性病变通常会产生令人反感的臭味。
Although the occurrence of severe generalized alopecia, lichenification and hyper-pigmentation in the West Highland white terrier breed has been reported previously as a form of genetic epidermal dysplasia, many veterinary clinicians believe this condition is a severe manifestation of allergic skin disease and concurrent Malassezia dermatitis. Similarly, historical reports of an idiopathic seborrhea non-responsive to etretinate in West Highland white terriers and basset hounds may have reflected untreated Malassezia dermatitis.
虽然曾经有报道西高地白㹴有严重的全身性脱毛、苔藓化和色素沉着的发生，但这作为这个品种遗传性表皮发育不良的一种形式。许多临床兽医相信这种疾病是过敏性皮肤病并发马拉色菌皮炎的严重表现。同样，在西高地白㹴和巴吉度猎犬的特发性皮脂溢中对依曲替酯无效的病史报告可能反映了未经治疗的马拉色菌皮炎。
Malassezia overgrowth in the ears typically results in a pruritic, erythematous, ceruminous otitis externa which results in the accumulation of a brownish discharge. As on the skin surface, the medial aspect of the pinna can become lichenified in chronic cases.
耳道中的马拉色菌过度增殖通常会导致瘙痒、红斑、耵聍性外耳炎，从而导致褐色分泌物堆积。如皮肤表面，在慢性病例中耳廓的内侧会变成苔藓化。
It is uncertain how the range of immunological hyperresponsiveness to M. pachydermatis present in dogs with Malassezia dermatitis (none, immediate, delayed, contact; Section 6) influences the spectrum of lesion type and severity in affected dogs.
尚不能确认患有马拉色菌皮炎（无、速发、迟发、接触见第六节）的犬对于厚皮马拉色菌存在的免疫高应答性的范围如何影响患病犬的病变类型和严重程度。
Figure 4. Malassezia dermatitis in the neck fold of a bull mastiff. There is a localized and demarcated area of focally intense erythema of thickened skin, with mild alopecia and kerato-sebaceous material matting the remaining hairs.
Fig 4 一只雄性牛獒犬颈部的马拉色菌皮炎。这是一个局部、皮肤增厚局灶性红斑界限清晰的区域且伴随轻度脱毛、角化皮脂性皮屑使其毛发不具有光泽。
Figure 5. Malassezia paronychia in a dog characterised by brown discolouration of the proximal claw.
Fig 5 爪部近端棕色变色特征显示为马拉色菌甲沟炎。
Figure 6. Malassezia dermatitis affecting the axillae of an atopic West Highland white terrier.The chronic lesions are characterized by symmetrical areas of intense hyperpigmentation, severe lichenification，erythema and tightly adherent crust.
图 6 患马拉色菌皮炎西高地白㹴腋窝。慢性病变以色素沉着、严重的苔藓化病变、红斑、附着结痂的对称区域为特征。
12.4 Concurrent diseases
12.4并发症
Many dogs with Malassezia dermatitis have concurrent dermatoses, especially hyper-sensitivity disorders, ectoparasitic infestation, bacterial pyoderma, endocrinopathies or cornification defects (Section 7). This can complicate the diagnosis, or lead to misdiagnoses, due to overlapping of clinical signs. These diagnostic challenges are compounded by lack of direct correlation between yeast population density and clinical signs (Section 8.5).However, it is also important to remember that in some cases, especially in predisposed breeds, there is no identifiable underlying cause and the dog’s skin disease may respond completely to antifungal therapy.
许多马拉色菌皮炎患犬均有皮肤病的并发症，尤其是过敏性疾病、体外寄生虫、细菌性脓皮病、内分泌疾病或角化异常（第7节）。由于临床症状的叠加这使得诊断复杂化或导致误诊。酵母菌菌体密度和临床症状之间缺乏相关性，这些增加了诊断难度（第8.5节）。然而在某些情况下记住这些也是重要的，特别是在易感品种中，没有识别潜在病因，但犬皮肤疾病可能会对抗真菌治疗产生完全的反应。
12.5 Conclusions: clinical presentations in dogs
12.5结论：犬的临床表现
Erythema, usually with kerato-sebaceous scale, and pruritus (minimal, mild, moderate or severe) dominates the clinical presentation, often favouring intertriginous zones.There may be concurrent hyperpigmentation，lichenification , malodour , traumatic alopecia and otitis externa. Some cases present with paronychia with claw fold erythema and swelling, waxy or crusty brown exudate, red-brown claw staining, or frenzied facial pruritus with varying, sometimes subtle, cheilitis or erythema of chin/ perioral skin.
红斑通常伴随角化皮脂性皮屑，且瘙痒（最低、轻度、中度、重度）这些占据主要症状，通常会发生在皮肤摩擦区域。可能同时出现色素沉着、苔藓化、恶臭、外伤性脱毛和外耳炎。一些病例出现甲沟炎伴随爪部褶皱部红斑、肿胀、蜡状或形成结痂的棕色分泌物或不同程度较为狂躁的面部瘙痒伴随不同程度的唇炎，有时不太明显，或下巴/口周皮肤的红斑。
13 Clinical presentations in cats
13 猫的临床表现
13.1 Malassezia dermatitis and paronychia
13.1马拉色菌皮炎和甲沟炎
The clinical presentation of feline Malassezia dermatitis varies markedly depending on the underlying disease (Section 7). Malassezia yeasts (chiefly M. pachydermatis) have been associated with a greasy seborrhoeic dermatitis in cats with or without concurrent paronychia.Predisposing diseases include poorly defined genetic factors (in Devon Rex and sphynx cats), feline atopic dermatitis (which may present with concurrent bacterial pyoderma), adverse food reaction, flea bite hypersensitivity, although some recurrent cases are idiopathic despite diagnostic investigation.There is conflicting evidence for diabetes mellitus as a predisposing cause. Feline immunodeficiency virus positive cats have been shown to carry more Malassezia organisms compared with normal cats but this was not associated with any clinical signs.
猫马拉色菌皮炎的临床表现根据潜在疾病而不同（第7节）。马拉色酵母菌（主要是厚皮马拉色菌）与伴有或不伴有甲沟炎的油性脂溢性皮炎患猫有关。易感疾病包括定义不明的遗传因素（德文卷毛猫和斯芬克斯）、猫特应性皮炎（可能并发细菌性脓皮病）、食物不良反应、跳蚤叮咬性过敏，但一些复发病例经过诊断调查判断为特发性的。糖尿病是易感因素的证据是相互矛盾的。与正常猫相比，猫免疫缺陷病毒阳性的患猫携带更多的马拉色菌，但这与任何临床表现无关。
Affected Devon Rex and sphynx cats typically show mild to marked greasy seborrhea with alopecia (in Devon Rex) and hyperpigmentation or reddish-brown surface discolouration and variable erythema affecting the axillae, groin, ventral neck and predominantly ventral interdigital regions. This is commonly accompanied by a greasy, tightly adherent brown exudate on the claws and/ or in the claw folds of multiple digits. Pruritus is not typically a feature.
患病的德文卷毛猫和斯芬克斯猫表现出轻度至明显的油性脂溢性皮炎伴有脱毛（德文卷毛猫）和色素沉着，或表面变为棕红色、患病的腋窝、腹股沟、颈腹部和主要是指间腹侧出现不同程度的红斑。通常在爪部和/或多个指爪部皱褶处表现油腻、附着棕色分泌物，瘙痒通常不是典型特征。
Less common presentations reported in Devon Rex cats include generalized seborrhea sicca, a greasy seborrhea affecting the ventral neck and head and pruritus. In sphynx cats in particular, there may be some elevated Malassezia carriage (compared with normal cats) which may result in greasiness without overt inflammation or seborrhoea.
在德文卷毛猫中不常见的报告包括：全身性干性皮脂溢、颈腹侧和头部油性皮脂溢和瘙痒。特别在斯芬克斯猫马拉色菌携带者（与正常猫相比）更高一些，可能会导致皮肤油腻而没有明显炎症或皮脂溢。
Allergic cats show more variability in their presentation and may present with concurrent bacterial pyoderma. Dermatitis may be localized or generalized with pruritus, alopecia, erythema and greasy exudate. The most commonly affected body regions include the face, chin, neck, limbs, abdomen and ear canals (see below).Less commonly affected regions include the tail and the pinnae, and in contrast with Devon Rex and sphynx cats, the interdigital regions and claw folds. Although uncommon, Malassezia overgrowth should be considered in every case of localized or generalized erythema associated with seborrhea in cats.
过敏症患猫表现出更多的易变性，可能会并发细菌性脓皮病。皮肤病可能是局部或全身性，伴有瘙痒、脱毛、红斑、油性渗出物，最常见患病部位包括：面部、下巴、颈部、四肢、腹部和耳道（见下文）。不常见患病区域包括：尾巴和耳廓，以及与德文卷毛猫和斯芬克斯猫不同，指间区域和爪部皱褶不常见。虽然不常见，但猫马拉色菌过度增殖应该每个局灶或全身性红斑，伴有皮脂溢的猫中进行鉴别诊断。
13.2 Feline idiopathic facial dermatitis
13.2猫特发性面部皮炎
Feline idiopathic facial dermatitis is an uncommon skin disorder of presumed hereditary origin. Persian, and anecdotally Himalayan, cats are predisposed. Affected cats show progressive skin lesions on the face characterised by symmetrical erythema and exudate with black waxy material matting the distal hair particularly in facial folds, perioral, periocular and preauricular regions. Secondary excoriations may be present in severe cases. A concurrent bilateral erythematous otitis with black waxy exudate was reported in seven of 13 cats.
猫特发性面部皮炎猜测是一种遗传起源的不常见皮肤疾病。波斯猫和喜马拉雅猫是易感品种。患猫表现猫在面部的进行性皮肤病变，特征为对称性红斑、渗出液和黑色蜡样分泌物与远端毛发纠缠在一起，尤其是面部褶皱、口部、眼周、耳前。在严重的病例中可能存在继发抓痕病变。已经报告中13只猫有7只并发双侧红斑性耳炎且伴有黑色蜡状渗出物。
Malassezia overgrowth has been found with cytology methods in approximately half of the reported cases, and more often with concurrent coccoid and/or rod bacterial overgrowth. In one study five of 12 cats partly responded to antimicrobial agents. Of these cats, four received ketoconazole 10 mg/kg for 14–42 days either alone (2/4 cases) or with concurrent antibiotics (two of four cases).A partial reduction in pruritus and exudate was noted in three of four cats. A 2% chlorhexidine 2% miconazole shampoo three times weekly in one case was used to a good initial response but was subsequently withdrawn due to irritation. It was concluded based on the partial responses seen in some cats that concurrent infection may be a complicating factor in this disease.
约一半的病例报告中通过细胞学方法发现了马拉色菌过度增殖，且更常见并发球菌或杆菌的过度增殖。在一项研究中12只猫有5只对抗菌药物有部分反应，这些猫中4只单用（2/4例）酮康唑10mg/kg，连续14-42天或同时口服抗生素（2/4例）。4只猫中有3只的瘙痒和渗出物部分减少，其中一例每周三次使用2%氯己定和2%咪康唑香波洗浴，最初反应良好，但后来由于刺激而取消。并发感染可能是该病的复杂因素，这是基于一些猫的部分反应得出的结论。
13.3 Feline paraneoplastic alopecia
13.3猫副肿瘤性脱毛
Feline paraneoplastic alopecia is a clinically distinct disease that occurs secondary to carcinoma of the liver, bile duct, intestine and pancreas, as well as with a neuroendocrine pancreatic carcinoma and hepatosplenic plasma cell tumour. The typical clinical presentation is of ventral alopecia with inelastIt is a non-pruritic disease unless there is significant secondary Malassezia (or bacterial) infection, usually manifest by crusts and brown exudate. Systemic azoles (itraconazole 5–10 mg/kg once daily and ketoconazole 5 mg/kg twice daily ) have been used in a limited number of cases to successfully treat concurrent Malassezia infections, resulting in reduced pruritus, better quality of life and reduction of inflammatory changes on histopathology, albeit without improving the poor prognosis associated with frequently metastatic neoplasia.
ic, thin, smooth and shiny but not fragile skin; adjacent hairs can be easily epilated. Limbs, paws and ears may be variably affected and dry crusting and fissuring of the footpads is occasionally noted.
猫副肿瘤性脱毛是一种继发于肝脏、胆管、肠、胰腺等肿瘤的临床明显疾病，除此之外还有神经内分泌胰腺癌和肝脾浆细胞癌。典型临床表现为腹侧脱毛且皮肤无弹性、较薄、光滑且有光泽，但皮肤不脆弱且周边毛发容易脱毛。四肢、爪部、耳部可能受到不同程度的影响以及偶见皮肤干燥和脚垫开裂。除非有显著的继发马拉色菌（或细菌）感染，否则是非瘙痒性疾病。通常表现出结痂和棕色分泌物。在少数情况下全身性使用唑类药物（伊曲康唑5-10mg/kg/qd，酮康唑5mg/kg/bid ）会成功治疗并发的马拉色菌感染，以减少瘙痒。改善生活质量以及在组织病理学上减少炎症的变化，但没有改善预后不良但这与频繁肿瘤转移有关。
13.4 Thymoma-associated exfoliative dermatitis
13.4胸腺瘤相关表皮剥脱性皮炎
Significant colonisation of the skin with Malassezia organisms may be associated with some cases of thymoma-associated exfoliative dermatitis. This is a paraneoplastic syndrome characterised by a generalised marked inflammatory exfoliation with patchy hair loss and easily epilated hair, and variably thickened skin which may be fissured or ulcerated. While this disease has been reported a number of times, only two reports confirmed associated Malassezia overgrowth. The remaining reports could not definitively confirm the presence of a thymoma, or failed to demonstrate yeast on histopathology, though skin cytology and/or culture was not noted to be performed in all cases.
马拉色菌在皮肤上的显著定植可能与某些胸腺癌相关的表皮剥脱性皮炎病例有关。这是一种副肿瘤综合症，其特征是全身性明显的炎性表皮剥脱伴有片状脱毛和毛发易拔除，以及不同程度皮肤增厚，伴有开裂或溃疡。尽管已经多次报道这种疾病，但只有两篇报告证实了相关的马拉色菌过度增殖，其他的报告则无法证实是否存在胸腺瘤或没有在组织病理学上证实酵母菌的存在，皮肤细胞学/或培养不是在所有情况下都需要进行。
A single cat with thymoma and confirmed Malassezia overgrowth (confluent growth on contact plates) that was treated surgically and followed up showed no yeast growth on contact plate culture six months following surgical removal. The only additional treatment for the M.pachydermatis initially isolated in this time was two baths in a selenium sulphide shampoo, indicating a likely strong association between yeast overgrowth and the thymoma.
一只患有胸腺瘤的猫确认了马拉色菌的过度增殖（接触板上混合生长），其经过外科治疗后随访显示在切除后六个月培养中没有发现马拉色菌。对于厚皮马拉色菌最初治疗的时间里只补充治疗两次硫化硒香波药浴，这表明酵母菌过度增殖与胸腺瘤之间可能存在很强的联系。
13.5 Superficial necrolytic dermatitis
13.5浅表坏死性皮炎
Superficial necrolytic dermatitis (syn. necrolytic migratory erythema, metabolic epidermal necrosis) has been very rarely reported in cats, in association with pancreatic carcinoma, thymic amyloidosis, hepatopathies and intestinal lymphoma. Clinical signs include scaling and variable alopecia of the trunk and limbs, with or without pruritus, and ulceration and crusting of the oral mucocutaneous junctions and interdigital regions. Two authors have reported secondary Malassezia dermatitis in conjunction with this presentation.
浅表坏死性皮炎（同坏死松解性游走性红斑、代谢性表皮坏死）在猫中非常罕见，与胰腺癌、胸腺淀粉样变性、肝病和肠淋巴瘤有关。临床症状包括躯干和四肢皮屑和不同程度的脱毛，伴有或不伴有瘙痒，口腔皮肤粘膜交界处和指间区域的溃疡和结痂。两位作者报告了与此表现相关并发继发性马拉色菌皮炎。
13.6 Feline acne
13.6猫痤疮
Malassezia organisms have been identified with cytology methods and/or histopathology in 16% (four of 25) to 18% (four of 22) of reported cases of feline acne. Malassezia organisms in feline chin acne have been identified not only on the skin surface, but also occasionally within comedones. There is some debate over the role of the pathogenicity of Malassezia spp. in chin acne, although two cases were reported in conference proceedings which responded poorly to antibiotics, had yeast organisms on both histopathology and cytology samples, and showed a good clinical and mycological response to a 30 day course of oral ketoconazole.
在报告的猫痤疮病例中16%（4/25）-18%（4/22）通过细胞学方法/或组织病理学鉴定了马拉色菌。猫下巴痤疮不仅会在皮肤表面会发现马拉色菌，而且粉刺里也有。马拉色菌在下巴痤疮中的致病性一直存在争议，但在会议论文中记录了两例对抗生素治疗无效的案例，且在组织病理学和细胞学中都发现了酵母菌以及在口服酮康唑30天发现对真菌治疗反应良好。
13.7 Otitis externa
13.7外耳炎
Malassezia pachydermatis is the predominant Malassezia yeast isolated from cats’ ears; frequency of isolation is increased in cats with otitis externa. In addition, M. furfur has been isolated from the ear of a healthy cat, whereas M. sympodialis and M. nana have been recovered from both healthy cats and cats with otitis externa. Whilst many healthy cats have ear canals apparently devoid of Malassezia yeasts, despite attempts to associate particular yeast counts with ear disease, there is a subset of cats which can carry large numbers of yeast in their ear canals without evidence of otitis externa. It has been suggested that the finding of excessive otic Malassezia organisms in the absence of clinical signs may potentially be indicative of occult systemic disease.
厚皮马拉色菌是猫耳道中分离出来的主要的马拉色酵母菌，这使得猫患外耳炎的频率增加。此外在健康的猫耳道中分离出糠秕马拉色菌，而健康的猫和患有外耳炎的猫均分离出合轴马拉色菌和娜娜马拉色菌。许多健康的猫耳道中没有马拉色菌，尽管尝试将特定的酵母菌计数与耳病联系起来，但有些猫可能携带大量马拉色菌而没有外耳炎的表现。有建议指出发现大量马拉色菌而没有临床症状可能指示存在潜在性全身性疾病。
Some feline cases of otitis externa are associated with Malassezia yeasts as the sole pathogen, whereas concurrent bacteria and/or Otodectes cynotis mites are commonly identified. Affected cats usually present with excessive dark to black waxy to flaky exudate, erythema, with variable otalgia, canal wall hyperplasia, pruritus and odour. Underlying diseases or co-morbidities include otoacariasis, atopic dermatitis, and feline idiopathic facial dermatitis, although some cats have no identified predisposing diseases. Interestingly, unlike the situation in seborrhoeic basset hounds, there is no evidence for an increased prevalence of Malassezia otitis in seborrheic Devon Rex and sphynx cats prone to Malassezia dermatitis.
一些猫外耳炎的案例与马拉色菌有关，且是唯一的病原体，通常可以识别并发的细菌/或耳螨病。患病猫通常存在深色至黑色蜡样至片状渗出物、红斑、不同程度的耳痛、耳道增生、瘙痒和异味（臭味）。潜在疾病或并发症包括：耳螨、特应性皮炎、猫特发性面部皮炎，但有些猫没有确定的易感疾病。有趣的是与皮脂溢的巴吉度情况不同，没有证据表明在皮脂溢的德文卷毛猫和马拉色菌皮炎的斯芬克斯猫中对于马拉色菌外耳炎的患病率增加
13.8 Conclusions: clinical presentation in cats
13.8结论：猫的临床表现
Erythema, usually with kerato-sebaceous scale, and pruritus (minimal, mild, moderate or severe) dominates the clinical presentation. There may be concurrent otitis externa and an observed breed predilection (Devon rex,sphynx). Malassezia dermatitis might feature in cats that present with a phenotype of allergic skin disease, idiopathic facial dermatitis (Persian/ Himalayan), feline acne and serious internal medical disorders such as feline paraneoplastic alopecia and thymoma-associated exfoliative dermatitis.
红斑通常伴有的角化皮脂性皮屑和瘙痒（轻微、轻度、中度、严重）占据了主导症状。可能并发外耳炎以及出现的品种偏好（德文卷毛和斯芬克斯）。马拉色菌皮炎可能出现在过敏性皮肤疾病表型、特发性面部皮炎（波斯猫/喜马拉雅猫）、猫痤疮、严重的内科疾病，如副肿瘤性脱毛和胸腺瘤相关的表皮剥脱性皮炎的猫中。
14 Summary of the diagnostic approach
14诊断方法的概要
14.1 Dog or cat presents with inflammatory skin disease potentially associated with Malassezia yeasts
14.1犬或猫可能与马拉色酵母菌相关的炎性皮肤病的表现
Clinical features are summarised in Sections 12.5 and 13.8.
第12.5节和第13.8节概述了临床症状
14.2 Establish whether Malassezia yeasts can be identified cytologically (or by quantitative culture using contact plates or detergent scrub; not routine swab culture) in lesional areas. Counts may be high but not necessarily so
确定病变区域细胞学检查是否有马拉色酵母菌（或使用接触板定量培养或浸湿的棉拭子；不是常规拭子培养），计数可能很高但未必如此。
Yes: Initiate trial therapy with appropriate topical and or systemic antifungal product.
No: Sample more sites; use an alternative sampling method; reconsider diagnosis.
存在：适当的开始外部或全身性抗真菌治疗
没有：采集更多样本；使用替代采样方法；重新诊断。
Additional diagnostic evaluations and treatments may be indicated at first presentation depending on the clinical signs, including cases where signs suggest, for example, paraneoplastic disorders in cats.
附加诊断评估和治疗可能根据首诊临床表现，包括病例症状提示，如猫副肿瘤性疾病。
14.3 Evaluate the clinical and mycological response to appropriate topical (three to four weeks) and or systemic (two to four weeks) antifungal therapy
14.3临床评估和对抗真菌药外部治疗（3-4周）和/或全身治疗（2-4周）真菌学疗效
1 Complete clinical & mycological response – diagnose Malassezia dermatitis; consider an underlying cause.
1．完整的临床&真菌学反应-诊断马拉色菌皮炎；考虑潜在病因。
2 Partial clinical, complete mycological – diagnose Malassezia dermatitis; investigate/treat ongoing underlying skin disease.
2．部分临床以及完整的真菌学反应-诊断马拉色菌性皮炎；调查/治疗正在进行中潜在皮肤疾病。
3 No clinical response, complete mycological - consider yeast presence incidental to other inflammatory disease.
3．无临床反应以及完整的真菌学反应-考虑其他炎性疾病附带的酵母菌。
4 Partial clinical & mycological response – suspect Malassezia dermatitis; review compliance; extend or intensify antifungal therapy.
4．部分临床&真菌学反应-疑似马拉色菌皮炎；评估依从性；扩大或加强抗真菌治疗。
5 Neither clinical or mycological response – review compliance; consider abnormal drug absorption or metabolism, or drug resistance; change antifungal treatment and re-assess.
5．临床和真菌学均无反应-评估依从性；考虑药物吸收异常或代谢或耐药；改变抗真菌治疗并重新评估。
15 Therapy
15治疗
15.1 General considerations
15.1概述
Treatment of Malassezia dermatitis typically involves the use of topical and/or systemic antifungal medications. Topical treatments such as shampoos, gels and lotions are appropriate for Malassezia dermatitis since the yeast is located within the stratum corneum. Shampoos are particularly interesting because they have a mechanical action that may reduce scaling and greasy exudation;some are formulated with keratoregulating agents such as phytosphingosine, ammonium lactate, zinc gluconate and salicylic acid.Although some clinicians favour other topical formulations and combinations (such as mousse, wipes, sprays, particularly in skin folds), these products currently require further evaluation to justify their therapeutic recommendation. Systemic therapies are often more expensive than topical therapies but may be necessary in cases where topical therapy is challenging for the owner/patient affiliation or otherwise ineffective. However, a combined topical/systemic approach may be optimal in some dogs with generalized and/or severe lesions: one study (published in abstract form) showed that a combination or oral ketoconazole and 2%miconazole /2% chlorhexidine shampoo was more effective and allowed a better speed of cure than either topical or systemic treatment used alone. It is also important to diagnose and treat the underlying cause responsible for the proliferation of the yeast (Section 7).
马拉色菌皮炎的治疗通常涉及外部或全身性抗真菌药物的使用。外部治疗如香波、凝胶、洗剂均适用于马拉色菌皮炎的治疗，因为酵母菌存在于角质层内。香波特别有趣的是因为他们具有机械作用，这样可以去除污垢和渗出的油脂。一些含有混合角质调节剂，如植物鞘氨醇、乳酸铵、葡萄糖酸锌和水杨酸。虽然某些临床医生偏爱其他外部剂型和组合剂型（如摩丝、湿巾、喷雾剂，尤其在皮肤褶皱中使用），但这些产品需要进一步证明他们的治疗建议。全身治疗较于外部治疗费用较高，但在外部治疗对于动物主人/患病动物依从性或其他方面无效且具有挑战性时可能是有必要的。但结合外部和全身性治疗在某些有全身性或严重病变的犬中可能是最佳途径：一项研究显示（以概要形式发表）结合或口服酮康唑和2%咪康唑/2%氯己定香波比单独使用外部或全身性治疗更有效，治愈速度更快。诊断和治疗潜在疾病也同样重要（第7节）。
15.2 Development of the consensus on therapy
15.2治疗共识发展
Many in vitro studies have been published showing the potential activity of various molecules against yeast and notably Malassezia spp. (reviewed in Section 10). Unfortunately trials assessing the in vivo efficacy of antifungal treatment for Malassezia dermatitis in dogs are few in number and commonly involve only small group sizes with resultant low statistical power. This is quite surprising if we consider that Malassezia dermatitis is a very common condition in veterinary medicine. In cats data are even less numerous and only open studies have been reported.
许多已经发表的体外研究显示各种抗菌分子对酵母菌潜在活性，尤其是马拉色菌属（见第10节），不幸的是，评估犬马拉色菌皮炎抗真菌药物体内治疗效果的试验较少，通常小组规模使统计功效低下。如果我们认为马拉色菌皮炎在兽医中较为常见这是令人意外的。仅有的公开报告中猫的数据更少。
The authors approached the development of consensus guidelines on therapy on two levels. Firstly, we performed a systematic search and review of relevant published trial data with grading of the study quality to provide evidence based conclusions on the strength of recommendation, updating a previous review. Secondly, we provided summary practice guidelines that are primarily evidence-based and drawn from part one and included a component of expert opinion where the evidence based data is limited or absent. Consequently, the concluding summary is a combination of evidence base and consensus of opinion.
作者从两个方面制定治疗共识指南，首先在我们将相关已发表的实验数据以及研究质量的等级报告用以提供基于推荐强度的循证结论的系统检查和评价，进行更新之前的报告。其次当循证数据有限或缺乏时我们提供主要的循证和引自第一部分以及包含专家意见组成部分的总结常规指南。因此结论的摘要是循证和意见共识的共同组合。
For the systematic review we utilised the Strength of Recommendation Taxonomy (SORT), a comprehensive taxonomy for evaluating the strength of recommendation based on a body of evidence and the quality of individual studies (Table 2).This schedule emphasises the use of patient-oriented outcomes and is designed to simplify the interpretation of studies and facilitate their incorporation into evidence-based patient care. Studies for review were identified by electronic searches of the PubMed (National Center for Biotechnology Information, US National Library of Medicine 8600 Rockville Pike, Bethesda MD 20894,USA) and CAB Direct (Centre for Agriculture and Bioscience International, Wallingford, UK) databases (keywords were Malassezia, treatment, dog, cat) and manual searches of Advances in Veterinary Dermatology, Volumes 1–8 (no relevant studies identified). The studies were included if presented in full or abstract form in a peer-reviewed journal; studies presented only in conference proceedings were not evaluated due to likely infrequent availability to the wider veterinary dermatology community.
对于系统回顾我们利用分类推荐强度（SORT），综合分类用于评估基于大量证据和个别研究质量的推荐强度（table 2）。这个记录表强调以患者为导向的结果以及旨在简化研究的说明，促进他们并入循证的患者护理。由PubMed和CAB Direct数据库（关键词：马拉色菌，治疗，犬、猫）电子搜索以及《兽医皮肤病学进展》Volumes 1–8（未找到相关研究）中确定审查回顾。研究包括如果在同行评审期刊中以完整或摘要的形式呈现；仅在会议记录中进行的研究没有评估是由于对于兽医学界可能有少见的有效性。
Table 2 . (a) The Strength of Recommendation Taxonomy (SORT)
(b) descriptors for Levels of Evidence (LoE) for individual studies
(a) Strength of Recommendation 推荐强度 | Definition 2 定义 |
| Based on consistent and good quality patient-oriented evidence 基于一致和高质量患者为核心证据 |
| Based on inconsistent or limited quality patient-oriented evidence 基于不一致或以有限品质患者为核心证据 |
| Recommendation based on consensus, usual practice, disease-oriented evidence or case series 基于共识建议、惯例、以疾病为导向或病例系列。 |
(b) Level of Evidence 证据等级 | Definition for treatment studies 2 治疗研究定义 |
1 – Good quality patient-oriented 以优质的患者为核心 | High quality individual RCT, or meta-analysis of consistent RCTs 高质量单独的随机对照试验或一致性随机对照试验的荟萃分析 |
2 - Limited quality patient-oriented 以有限品质患者为核心 | Lower quality clinical trial, cohort study, case-control study 低质量临床试验、队列研究、案例对照研究 |
| Recommendation based on consensus, usual practice, disease-oriented evidence or case series 基于共识的建议、惯例、以疾病为导向或病例系列。 |
RCT randomized controlled trial.随机对照试验
15.3 Review of trial data in dogs: systemic treatments
15.3犬实验数据的回顾：全身性治疗
15.3.1 Azole derivatives
15.3.1唑类衍生物
Ketoconazole: In spite of the widespread practice use of ketoconazole to treat Malassezia dermatitis, only a few studies evaluated the efficacy of this azole in vivo. Studies were either randomized and controlled, or controlled without blinding (Table 3) involving relatively small group sizes (7-12 dogs). Together, these studies indicated that the use of ketoconazole at an oral dosage of 5–10 mg/kg/day is most often either completely or partially effective, when given fasted, to improve both clinical signs and cytological or colony counts from dogs suffering from Malassezia dermatitis (Strength of Recommendation (SoR) B-moderate).The length of treatment varied between three and four weeks in most cases. Whilst one un-blinded randomised study of 20 dogs suggested that there was no significant difference in efficacy between 5 and 10 mg/kg/day of ketoconazole administrated once daily for three weeks, there is insufficient evidence to comment specifically on the efficacy of the various doses used (5 or 10 mg/kg,once or twice daily). Reports of improved efficacy with KTZ at doses of 10 mg/kg twice daily do not appear to have been subjected to critical comparative trials. Adverse reactions are regularly reported with the use of ketoconazole in dogs; a retrospective study of 632 dogs that received a median daily dose of 10 mg/kg reported adverse effects in 14.6%, including primarily vomiting (7.1%), anorexia (4.9%), lethargy (1.9%) and diarrhea (1.1%). Adverse effects were significantly more frequent in dogs receiving concurrent ivermectin or ciclosporin.
酮康唑：尽管酮康唑广泛用于马拉色菌皮炎的治疗，但只有少数研究评估了这种药在体内的功效。研究是随机对照的或在不致盲（table 3）情况下在小范围群体中（7-12只）。总之这些研究表明使用酮康唑口服剂量为5-10mg/kg/d通常是完全或部分有效的，在空腹情况下临床症状和细胞学或患有马拉色菌皮炎的犬菌落计数同时改善（推荐强度（SoR）B-中等）。大多数情况下治疗时间在3-4周之间，然而在一项针对20只犬的无盲随机研究表明，酮康唑（KTZ）5-10mg/kg/d连续三周没有显著差异，没有足够证据显示各种剂量对于治疗效果的差异（5或10mg/kg,每日1或2次）。关于KTZ10mg/kg，每日两次疗效报告没有进行较为严格的疗效比较实验。在犬中经常会有使用KTZ的副反应报告；一项针对632只犬的回顾性研究，每日平均剂量10mg/kg不良反应率为14.6%，主要包括：呕吐（7.1%）、厌食（4.9％）、嗜睡（1.9％）和腹泻（1.1％）。同时联用伊维菌素或环孢素的犬中不良反应率更高。
Itraconazole: Itraconazole appears to be effective based on the few clinical trials that have evaluated its efficacy for the treatment of canine Malassezia dermatitis (Table 4; SoR B-moderate). Two were comparative versus ketoconazole. Therapeutic doses recommended are variable with 5 mg/kg once daily, or for two consecutive days a week, being most often used. In two relatively small studies there were no significant differences in any results between itraconazole pulse therapy (two days on, five days off) and the daily administration of either itraconazole or ketoconazole. The pulse therapy approach reflects predicted accumulation of this lipophilic drug in the stratum corneum and reduces costs and likely also side-effects of this relatively well-tolerated azole. Adverse effects seem to be less frequent with itraconazole compared to ketoconazole: transient vomiting and decreased appetite were relatively rare in the published studies (four of 49 cases).
伊曲康唑：根据一些评估治疗犬马拉色菌皮炎疗效的临床试验显示伊曲康唑似乎是有效的（表4 ，SoR B-中等），与酮康唑相比疗效同样良好；推荐治疗剂量为5mg/kg，每日一次，或常用每周连用两天。在较小范围的针对两种药物治疗的比较中伊曲康唑脉冲疗法（连续两天，停药五天）与每日口服伊曲康唑或酮康唑疗效无明显差异。脉冲疗法反应了预计这种亲脂性药物可以在角质层累积，且降低成本以及虽然相对耐受性良好但依然可能存在副反应。与酮康唑相比伊曲康唑的不良反应似乎较少，在已发表的研究中发现有较少的短暂性呕吐和食欲下降（49例中的4例）。
Fluconazole: Only one study evaluated the use of fluconazole for the treatment of Malassezia dermatitis in dogs. This double-blind randomized controlled study comprising 25 dogs showed that fluconazole at 5–10 mg/kg orally once daily administered with food was as effective as ketoconazole at 5–10 mg/kg orally once daily for controlling the clinical and cytological signs of Malassezia dermatitis (Table 5). Concurrent use of cefalexin in both treatment groups limits full clinical interpretation (LoE 2; SoR B-moderate). Transient side effects of vomiting [n = 5] and or diarrhoea [n = 2] were seen in six of 13 dogs.
氟康唑：只有一项研究是关于使用氟康唑治疗犬马拉色菌皮炎；这项由25只犬组成的双盲随机对照研究表明：5-10 mg/kg，每日一次与食物同食与口服KTZ5-10mg/kg，每日一次对于控制马拉色菌皮炎的临床症状和细胞学同样有效（表5）。两个对照组同时使用头孢氨苄治疗限制了全面的临床解释（LoE 2; SoR B-中等）；13只犬中6只正常，7只出现了呕吐[n = 5]或腹泻[n = 2]的短暂副作用。
15.3.2 Allylamine derivatives
15.3.2烯丙基胺衍生物
Terbinafine: One study showed that oral terbinafine at 30 mg/kg orally once daily for 21 days reduced yeast counts (assessed by contact plates) in a group of seven basset hounds with high skin population densities of M.pachydermatis but without dermatitis; mycological efficacy was numerically but not statistically inferior to oral ketoconazole at 10 mg/kg once daily. This low-powered study was not included in the SORT analysis because the outcome is disease-orientated (yeast count) rather than patient-oriented (no clinical scoring) (Level of evidence (LoE) 3). The efficacy of terbinafine was subsequently assessed in two clinical trials, either randomized and controlled by a different interval of dosing of terbinafine, or in a small study with concurrent cefalexin therapy (Table 5; SoR C-weak).Monitoring of serum hepatic enzymes has been recommended for dogs receiving daily oral terbinafine in view of reports of reversible, mild-moderate elevations of alanine aminotransferase and serum alkaline phosphate. A study designed to integrate pharmacokinetic data with previous MIC data in 10 healthy dogs treated with 30 mg/kg orally once daily for 21 days indicated that terbinafine does not achieve high stratum corneum and sebum concentrations compared with serum values; achieved concentrations barely exceeded previously reported in vitro MIC values. These and other pharmacokinetic data might indicate preferential utility for systemic mycoses, or the need for further dose optimisation for superficial mycoses in dogs.
特比奈芬：一项针对一组7只患有厚皮马拉色菌过度增殖（接触板评估）且没有皮炎表现的巴吉度犬研究表明，口服特比奈芬30 mg/kg，每日一次连续21天后酵母菌有所减少。真菌学疗效在数字上不亚于口服酮康唑10mg/kg，每日一次,这个低效研究中未包括SORT分析，因为结果是以疾病为导向（酵母菌计数）而非以患者为导向（无临床评分）（证据等级（LoE）3）。随后在两项临床试验中对特比萘芬进行了功效评估，随机以及调控不同剂量的特比奈芬或在小型研究同时口服头孢氨苄 (表5; SoR C-弱)。对于每日口服特比奈芬的犬可能会出现ALT和ALP的轻度至中度可逆性升高，因此血清肝酶的监测是被推荐的。一项在10只健康犬每日口服30mg/kg的剂量进行21天的研究中旨在整合药代动力学数据和MIC（最低抑菌浓度）数据显示与血清值相比特比奈芬不能达到较高的角质层和皮脂浓度。这些和其他药代动力学数据可能表明全身性真菌病或需要进一步优化治疗的犬浅表性真菌感染是优选方案。
15.4 Review of trial data in dogs: topical treatments
15.4回顾犬的实验数据：外部治疗
15.4.1 Miconazole and chlorhexidine
15.4.1咪康唑和氯己定
Miconazole is an azole derivative present in various shampoos, creams or lotions. A combination of 2% miconazole and 2% chlorhexidine in a shampoo formulation is licensed for the treatment of canine Malassezia dermatitis in a number of countries, primarily in Europe and Australia. Consistent high efficacy has been reported in randomised controlled trials (RCT) (Table 6; SoR A–strong). In one RCT study, clinical efficacy was associated with marked reductions in skin population densities of both M. pachydermatis and total bacteria/ staphylococci,assessed using a detergent scrub technique. In the second RCT, yeast counts were assessed by tape-strips whereas bacterial populations were not assessed. Adverse effects to miconazole/ chlorhexidine were not reported amongst the 48 dogs treated in these two studies, although the UK data sheet of the product used mentions ‘very rare’ or ‘exceptional’ pruritic or erythematous reactions (http://www.noahcompendium.co.uk/?xml:id=-449936)
咪康唑是一种存在于各种香波、霜或乳液中的唑类衍生物。在许多国家（主要是欧洲和澳大利亚）2%咪康唑和2%氯己定组合香波被批准用于治疗犬马拉色菌皮炎。在随机对照试验（RCT）中报告了一致性的良好疗效（表6 SoR A–强）。在一项RCT研究中，使用浸湿棉拭子进行评估，临床疗效与皮肤的厚皮马拉色菌和细菌总数/葡萄球菌的菌落明显减少有关。在第二项RCT中酵母菌计数是通过胶带进行评估，而菌落菌群未进行评估。这两项对48只犬的治疗研究中没有发现咪康唑和氯己定的不良报告。尽管在英国的数据中提到了关于罕见瘙痒和红斑的不良反应。
15.4.2 Other chlorhexidine products
15.4.2其他的氯己定产品
In a RCT, a 3% chlorhexidine shampoo was reported to be more than 50% effective in 18 of 22 treated dogs (Table 6; LoE 1; SoR B-moderate) and was judged not inferior to 2% miconazole and 2% chlorhexidine. Four dogs had transient and self-limiting side effects; the UK data sheet reports that self-limiting pruritus and erythematous reactions are ‘common’ and that conjunctival inflammation may occur. A 3% chlorhexidine and 0.5% climbazole shampoo was compared with a 2% miconazole and 2% chlorhexidine shampoo in a blinded design in 16 basset hounds (seven healthy, nine greasy) by a single application of each product to one side of the body. Both yeast counts (by contact plates) and clinical scores reduced during the fourth day trial period but clinical interpretation was limited by the varied clinical status of the subject dogs in this published abstract (LoE 3).
RCT 根据报道在22只经3%氯己定香波治疗的18只犬效果良好，有效率超过50%，所以认为效果不亚于2％咪康唑和2％氯己定混合香波(表6; LoE 1; SoR B-中等)。有四只犬被报告有短暂以及自限性的副反应，据英国的数据报道显示较为常见的是自限性的瘙痒和红斑且可能有结膜炎。16只双盲试验的巴吉度犬中（7只健康，9只油性皮肤）将每种产品涂抹身体的一侧进行3%氯己定和0.5%氯咪巴唑香波与2％咪康唑和2％氯己定香波治疗效果进行比较；两者进行酵母菌计数（接触板），临床评分在试验期的4天有所减少，但在这个发表的摘要中临床解释受到受检犬不同临床状况的限制(LoE 3)。
15.4.3 Miconazole
15.4.3咪康唑
A small RCT of 1% and 2% miconazole conditioners of low statistical power showed reductions in clinical scores and yeast counts but no statistical difference when compared with vehicle control (LoE 2).
当与空白对照相比低统计功效的1％和2％咪康唑香波的小随机对照试验显示临床评分和酵母菌计数减少但无统计学差异。（LoE 2）
15.4.4 Climbazole
15.4.4氯咪巴唑
A 2% climbazole shampoo had rapid mycological efficacy in a small disease-oriented (contact plate yeast count)rather than patient-oriented (no clinical scoring) RCT involving six treated and five control beagle dogs without skin lesions (SoR not applicable). Similarly, a short, open study of wipes containing 0.5% climbazole, 0.3% chlorhexidine and Tris-EDTA assessed only yeast counts but not clinical parameters.
一个小型以疾病为导向（接触板酵母菌计数）而不是以患者为导向（无临床评分）的RCT包括：6只治疗和5只控制且无皮损的比格犬（SoR不适用）2%氯咪巴唑香波具有快速的真菌学疗效。同样的含有0.5%氯咪巴唑、0.3%氯己定以及Tris-EDTA仅评估酵母计数但无临床参数。
15.4.5 Enilconazole
15.4.5恩康唑
A 0.2% enilconazole lotion is licensed in some countries for the topical therapy of dermatophytosis in dogs, cattle and horses. Only one retrospective study of 12 cases of generalised Malassezia dermatitis reported treatment with a 0.2% enilconazole lotion (frequency of application not detailed) in association with oral ketoconazole. Although a complete mycological recovery was described, no specific report of clinical improvement was available (LoE 3; SoR not applicable).
0.2%恩康唑洗剂在某些国家或地区已经被批准用于犬、牛、马的皮肤癣菌的外部治疗。仅有一项对于12例全身性马拉色菌皮炎的回顾性研究，报告治疗使用0.2%恩康唑（使用频率不详）联合口服酮康唑；尽管被描述为彻底恢复，但是没有临床改善的具体报告（LoE 3；SoR不适用）。
15.4.6 Others
15.4.6其他
In a RCT involving 35 dogs, 20 received a commercially-available mixture of essential oils (Malacalm, Flora Slr Oli essenziali, Lorenzana, Italy) twice daily for one month, 10 received oral ketoconazole 10 mg/kg orally once daily and 2% chlorhexidine twice weekly and five dogs served as untreated controls. Whilst the authors reported a >50% improve-ment in clinical scores in nine of 10 of dogs treated with essential oils, and in all of the dogs treated with ketoconazole and chlorhexidine, interpretation is limited by unclear randomisation and blinding procedures,and failure to report pre- and post-treatment group clinical scores (mean or median, range) in the three treatment groups (LoE 2; SoR C-weak). An unusual feature of this study was reported lack of relapse 150 days post-treat-ment in all of the essential oil-treated dogs. Further evaluation of this product is warranted.
在随机对照试验包括35只犬，20只使用市售精油混合物每天两次连续一个月，10只犬口服KTZ10mg/kg，每日一次，每周两次2%氯己定香波药浴，另外五只犬不治疗作为对照。作者报告在对9/10只犬使用精油的治疗之后临床评分改善50%以上，以及所有使用KTZ和氯己定治疗的解释受限于不明的随机及盲法程序，在三个治疗组中无法报告治疗前后的临床评分（平均值或中位数，范围）（LoE 2; SoR C-弱）。这项研究不寻常的特点就是报告中使用精油治疗的犬150天后没有发现复发，有必要对该产品进行进一步评估。
Selenium sulphide, piroctone olamine, benzalkonium chloride, triclosan formulated either in gels, shampoos, lotions, sprays or spot-on are also available but there is insufficient evidence to recommend their use at this time. In an open case series published in abstract form, a shampoo combination of piroctone olamine and ammonium lactate and a lotion (piroctone olamine and salicylic acid)reduced clinical scores and cytological yeast counts in 14 seborrhoeic dogs with high Malassezia counts (LoE 3); these data should be confirmed in a RCT.
含有硫化硒、吡罗克酮乙醇胺盐、苯扎氯铵、三氯苯氧氯酚的配方凝胶、香波、乳液、喷雾剂、滴剂也是可以使用，但目前没有足够证据推荐使用他们。以摘要形式公开发表的14只马拉色菌计数较高的皮脂溢犬案例中使用吡罗克酮乙醇胺盐、乳酸铵以及洗剂（吡罗克酮乙醇胺盐和水杨酸）会减少临床评分和细胞学酵母菌计数（LoE 3）；这些数据应在随机对照试验中确认。
15.5 Review of trial data in cats
15.5猫试验数据的回顾
In cats only open case series have been described, using oral itraconazole at varying doses and intervals (Table S7,LoE 3, SoR C-weak). As for dogs, topical antifungal agents such as miconazole, chlorhexidine or climbazole are likely to be beneficial but there is no data to substantiate this, other than anecdotal reports.
在仅有猫的公开案例中提及使用不同剂量和不同间隔的伊曲康唑（表S7,LoE 3, SoR C-弱），犬的外部真菌治疗如：咪康唑、氯己定、克霉唑可能是有益的，但没有任何数据可以证实这一点，除传闻的报告外。
15.6 Antifungal drug formulation
15.6抗真菌药物剂型
The relatively high cost of certain innovator-formulated drugs such as itraconazole has stimulated the compounding of bulk powder formulations by pharmacists in an attempt to reduce costs to clients. This is legal in some (but not all) countries under certain conditions. In a randomised cross-over study involving nine healthy beagle dogs, neither generic nor compounded itraconazole was bioequivalent to the innovator-formulated product. Pharmacokinetic analyses showed that the compounded formulation had very low absorption and bioavailability (5% of innovator product), yielding likely ineffective plasma concentrations, whereas the generic and reference products were broadly similar to each other. In a similar study of eight healthy cats, itraconazole compounded in both capsules and suspension was absorbed poorly and inconsistently. In a field study of 95 dogs and 20 cats receiving either compounded, generic or innovator-formulated itraconazole for systemic mycoses, subtherapeutic concentrations were detected in 95.2% of animals receiving the compounded formulation but in only 12.5% or less of the animals treated with generic or reference formulations. The poor bioavailability of itraconazole in compounded formulations and in some cases treatment failures, has been attributed to the absence of cyclodextrin, a carrier compound shown to improve gas-tro-intestinal absorption. A study of compounded fluconazole suspensions showed poor pharmaceutical accuracy (median 74% of target concentration). These data indicate that use of compounded azole formulations must not be used; innovator-formulated or proven generic formulations are preferred.
一些创新配方的药物成本相对较高，伊曲康唑促进了药剂师配制散装粉末制剂试图降低客户成本，某些条件下在某些（但不是全部）国家/或地区是合法的。在一个9只健康比格犬的随即交叉实验显示普通或复方伊曲康唑与创新制剂产品的生物等效是一样的。药代动力学分析表明该复合制剂的吸收和生物利用度非常低（仅为创新产品的5％），产生可能无效的血浆浓度，而通用和参考药品大体相同。在对八只健康猫的类似研究中，将伊曲康唑配置成胶囊和混悬液发现吸收不良和吸收不一致，在一项针对95只犬和20只猫的实验研究中对全身性真菌感染使用任意复方、普通或创新者配制的伊曲康唑，接受复合制剂的动物有95.2％中检测到亚抑菌浓度（最低治疗剂量是耐药的重要原因），但用普通或参考配方治疗的动物中只有12.5％或更少。在复方制剂的情况下伊曲康唑的生物利用度差以及在某些情况下治疗失败原因被归结于β-环糊精的缺乏，这种载体化合物可以改善胃肠的吸收。复方氟康唑悬浮液的研究表明药物的准确性差（目标浓度的中位数74％）这些数据表明不建议使用混合的唑类制剂。首选创新剂型配方或经过验证的普通配方。
There appears to be no published data on the comparative efficacy of different topical formulations containing the same or similar ingredients. This may be especially relevant with over-the-counter formulations where regulatory assessment of product quality may be less exacting and with molecules such as chlorhexidine whose stability may vary under different conditions. Both published RCT of a 2% miconazole and 2% chlorhexidine shampoo with strong evidence of efficacy utilised the same innova-tor-formulated licensed product (Malaseb, Derm-care Vet, Slacks Creek, Queensland, Australia); one of these studies also showed good activity from a licensed 3% chlorhexidine shampoo (Microbex?, VIRBAC SA,Carros, France).
不同的外部治疗包含相同或相似的配方比较效果似乎没有公开的数据。这可能与非处方配方特别相关，而产品质量的监管评估可能不太严格且有微小颗粒，如氯己定的稳定性在不同状态下可能有所不同。2％咪康唑和2％氯己定与使用相同的创新配方的产品在已发表的随机对照试验中显示了疗效的有力证据。另外一项研究显示使用3%氯己定香波具有良好的预后。
15.7 Conclusions: consensus guidelines for treatment of Malassezia dermatitis in dogs and cats
15.7结论：治疗犬猫马拉色菌皮炎的共识指南
Amongst the various treatments utilised for Malassezia dermatitis in dogs, strong evidence (SoR A) is available only for the use of a 2% miconazole and 2% chlorhexidine shampoo, used twice weekly (two RCT with LoE 1).This may be considered to be the topical treatment of first choice, where available and locally approved, and when owners are able to apply the product effectively. Moderate evidence (SoR B) is available for a 3% chlorhexidine shampoo (a single study of LoE 1).
犬的马拉色菌皮炎的各种治疗方法中有力的证据（SoR A）仅适用于使用2％咪康唑和2％氯己定香波，每周两次（两个RCT具有LoE 1）。可以考虑成为外部治疗的首选方法，且批准使用，以及当宠主能够有效使用产品。3％氯己定香波有中度证据（SoR B）（LoE 1的单项研究）。
For canine Malassezia dermatitis, there is moderate evidence (SoR B) for the use of ketoconazole at 5–10 mg/kg orally once or twice daily (five studies of LoE ≥ 2); and itraconazole at 5 mg/kg orally once daily or two consecutive days per week (two studies of LoE ≥ 2).Based on current limited evidence, the use of either of these two azoles is justified in canine cases and the final choice may depend on regional differences in availability, regulatory status and cost. Rationale for itraconazole instead of ketoconazole includes the potential for intermittent dosing and a perceived tendency for itraconazole to be better-tolerated. However, definitive statistical evidence of superior safety and/or efficacy is lacking and cost-benefit analysis makes ketoconazole a more practical choice in some countries. Compounded formulations must be avoided due to unreliable bioavailability. Evidence for fluconazole is limited to a single study (LoE 2) where it was used at 5–10 mg/kg orally once daily in conjunction with cefalexin. Thus fluconazole requires further assessment, especially since in vitro MIC values are routinely the highest amongst antifungal azoles utilized in veterinary medicine (See Section 10); this may correlate with intermittent anecdotal reports of treatment failures. Terbinafine warrants further evaluation due to partial beneficial effects in two trials (SoR C-weak) and questionable stratum corneum concentrations in a pharmacokinetic study when given at the current dose of 30 mg/kg orally once daily.
犬马拉色菌皮炎中等证据（SoR B）口服酮康唑5-10mg/kg，口服每日1次或2次(LoE≥2的五项研究)，伊曲康唑5 mg/kg，口服每日一次或每周连续口服两天（两项LoE≥2的研究）。根据目前有限的证据，在犬病例中使用这两种唑类是合理的，最终的选择可能取决于可用性、管理状态和成本方面的地域差异。ITZ替换KTZ的根本原因包括间歇性给药以及ITZ耐受性更好。然而高安全性的确实统计证据或在某些国家疗效的不足和成本的考虑使KTZ成为更实际的选择。由于生物利用度不高，应避免使用复合药剂。氟康唑的证据仅限于一项研究（LoE 2）5-10mg/kg，每日一次，且与头孢氨苄同服；因此氟康唑需要进一步研究，特别体外MIC值通常在兽医中是抗真菌药物唑类最高的（见第10节）。这可能与治疗失败的间歇性传闻有关。由于在两项试验中部分有效，以及在一项药代动力学研究中存在角质层浓度不确定，因此特比奈芬有必要进一步评估（SoR C-弱），目前剂量为30mg/kg，口服每日一次。
In cats, there is weak evidence only (SoR C) for the use of itraconazole at doses of 5–10 mg/kg orally once daily; or 5 mg/kg on a seven days on/ seven days off protocol. In view of this limited data, good safety profile and in line with guidelines for feline dermatophytosis, itraconazole should be considered as the systemic azole of first choice in this species for Malassezia dermatitis. Topical chlorhexidine and azole products have not been evaluated although their use is intuitive as adjunctive or sole treatments where application is practicable and clinically appropriate, such as in localized infections.
在猫中仅有少量证据（SoR C）表明伊曲康唑5–10 mg/kg，口服每日一次；或5mg/kg，每日一次连续7天，之后停药7天。由于数据有限，良好的安全性符合猫皮肤癣菌病指南，伊曲康唑应被考虑作为猫马拉色菌皮炎首选全身性唑类药物。外用氯己定和唑类产品尚未评估，但他们使用上来说直观的作为辅助或临床上切实可行的唯一方法，如局部感染。
16 Prevention of Malassezia-associated skin diseases in dogs and cats
16预防犬猫马拉色菌相关的皮肤疾病
16.1 Management of underlying diseases
16.1潜在疾病的管理
As Malassezia yeasts are part of the normal cutaneous microflora, complete elimination of the organism is unrealistic even with effective treatment. Relapsing infections are common where there is persistence of the underlying cause for the yeast overgrowth. The standard clinical approach is identification and treatment of underlying causes, whenever possible, though there is surprisingly limited reported evidence to document its efficacy (Table S8).
马拉色菌是皮肤微生物群的一部分，即使有效的治疗也无法完全清除该微生物。复发感染也是常见的，潜在的病因导致酵母菌的过度增值。标准的临床方法是在可能的情况下识别和治疗潜在病因，已经有证据显示出其效力（table S8）。
16.2 Topical therapy
16.3外部治疗
When predisposing factors cannot be identified or controlled in an animal suffering from recurrent Malassezia infections, regular topical or pulsed oral antifungal therapy have been recommended to minimise the frequency of infection relapses that cannot be managed by other means.
当复发性马拉色菌感染的动物无法确定易感因素或进行控制时，建议定期的外部或脉冲口服抗真菌治疗，以尽量减少无法通过其他方式进行管理的感染复发的频率。
Multiple topical therapies have been shown to be effective for treatment of Malassezia dermatitis in dogs and cats (See Section 15). In addition, because of a lower risk for toxicity, topical treatments have also been recommended (if practical and not causing irritation ) as preferable to systemic treatments for long-term therapy in chronically relapsing cases. Furthermore, there is evidence that bathing dogs in 2% chlorhexidine/2%miconazole shampoo every three days can reduce oral carriage of Malassezia organisms. However, recommendations for weekly antifungal shampoo bathing as a preventive strategy to reduce the frequency of recurrent Malassezia dermatitis appear anecdotal rather than evidence-based. Studies in vitro that demonstrate shampoo persistence on hairs may or may not be relevant to persistence on skin, and studies in vivo on topical therapy persistence were conducted in normal dogs rather than in dogs with Malassezia dermatitis.
多种外部治疗显示了对犬猫马拉色菌皮炎治疗是有效的（见第15节）.另外由于其低毒性，在慢性复发的病例中推荐使用外部治疗（如果可行也不会引起刺激）长期管理外部治疗优于全身性治疗。此外有证据表明每三天使用2％氯己定/2％咪康唑香波为犬洗澡可以减少马拉色菌的携带。然而建议每周使用抗真菌药浴香波是作为减少复发性马拉色菌皮炎发生频率的预防策略，这似乎是未经验证而不是基于循证的。体外研究表明香波在毛发的持久性与可能会或可能不会与皮肤持久性有关，并且在正常犬而不是患有马拉色菌皮炎的犬中进行外部治疗的持久性体内研究。
In a comparative study of a commercial mixture of essential oils (Malacalm; Flora s.r.l., Lorenzana, Pisa, Italy)applied twice daily for one month to 20 dogs with recurrent Malassezia dermatitis, and combined ketoconazole(10 mg/kg orally once daily) and 2% chlorhexidine shampoo (twice weekly) for 21 days in 10 dogs, both groups showed good clinical and cytological improvements at day 30. When reviewed at day 180, all conventionally treated dogs had reportedly relapsed whereas dogs treated with the essential oil formulation had not.Interpretation of this study is limited by incomplete randomization ,clinical and cytological data in the publication and an absence of within and between-group statistical comparisons at day 180-time point; consequently this treatment cannot be recommended for prevention without further critical assessment.
在商品性混合精油的比较研究中，对20只复发性马拉色菌皮炎的犬每天两次持续一个月，同时口服酮康唑（10mg/kg，口服每日一次）和2％氯己定每周两次连续21天，两组在第30天显示出临床症状和细胞学的良好改善。当在180天回访时发现，所有常规治疗的犬均复发，而使用精油治疗的犬未发现复发。这项研究的解释受不完全随机限制，在发表的临床和细胞学数据中，在180天时缺乏组内和组间的统计比较。因此，如果没有进一步的严格评估，就不能推荐这种方法来作为预防。
With respect to prevention of recurrent Malassezia otitis, while studies in vitro have demonstrated antimicrobial efficacy of ear cleaners, there are only two studies examining topical therapy for prevention of Malassezia otitis. A single study examining dogs with recurrent allergic otitis showed a favourable outcome to a once weekly ear cleaner containing chloroxylenol and cerumenolytics ( Epiotic/Virbac Carros/France) and concurrent twice weekly three drops per ear of 0.0584% topical hydrocortisone aceponate solution (Cortavance, VIRBAC SA, Carros, France) (95% chance of remaining free of relapse at day 180) compared with weekly ear cleaner alone (50%chance of remaining infection free at day 180). However, the lack of detail regarding the nature of the infection for both pre-treatment and relapsing otitis, makes a recommendation specifically for the prevention of Malassezia otitis difficult. A second open study examining twice weekly 2% acetic acid 2% boric acid topically showed the protocol unsuccessful in preventing relapse of Malassezia otitis beyond previously documented relapse intervals in six of eight cases.
关于预防复发性马拉色菌耳炎，体外研究发现耳部清洁剂有良好的抗菌能力，只有两项研究关于外部治疗用以预防马拉色菌耳炎，一项关于犬患有反复性过敏性耳炎的研究显示，每周一次使用包含对氯间二甲基苯酚和耵聍溶解剂以及与仅清洗耳道相比同时每周两次每个耳道三滴0.0584％外用氢化可的松醋丙酯溶液（180天时95%保持无复发）是有益的。然而缺乏有关治疗前和复发性耳炎的感染性质的细节，因此对于针对预防马拉色菌耳炎是存在困难的。第二个公开研究每周两次2％乙酸2％硼酸外部治疗显示8个案例中有6个复发间隔超过先前，该方案未能预防复发性马拉色菌耳炎。
16.3 Pulsed oral antifungal therapy
16.3脉冲口服抗真菌治疗
Oral antifungal drugs might be given by an intermittent/pulsed dosing schedule to try to prevent recurrent Malassezia dermatitis (and otitis) in dogs and cats, particularly where topical therapy is either ineffective or impractical. Overall, published evidence that substantiates the efficacy of this approach is lacking. Whilst the clinical risk appears low, it should be noted that intermittent use of oral antifungal drugs could potentially predispose to development of antifungal resistance (See Section 11). A dosing regimen of two consecutive days per week (“weekend therapy”) has been investigated or proposed for three oral antifungal drugs. Terbinafine (30 mg/kg orally once daily, two days on/ five days off) reduced yeast counts in tape-strips from dogs with Malassezia dermatitis but clinical resolution was considered complete in only one of 10 dogs at the end of 21 days. Whether pulse therapy with terbinafine might prevent relapse of previously resolved infections remains to be determined, but doubts over skin concentrations achieved with current doses 350 makes use of this drug questionable.
口服抗真菌药物可能通过间歇/脉冲的给药方案以尝试预防犬猫复发性马拉色菌皮炎（以及耳炎）；特别是外部治疗无效或不切实际的情况下。总而言之公开证据证实缺乏这种方法的有效性。同时临床风险似乎较低，应该注意的是间歇性口服抗真菌药物可能会导致耐药的发展（见第11节）。对于三种口服抗真菌药物连续使用两天（周末疗法）已经被研究或提出。对于患有马拉色菌皮炎的犬口服特比奈芬（30 mg/kg/qd连续两日，停药5日）之后使用胶带评估酵母数量有所减少，在21天结束时10只犬中仅一只被认为具有完全的临床消退。特比奈芬脉冲治疗是否可能会预防复发性感染还有待确认。但这种药物当前剂量能否达到超过皮肤浓是不确定的。
Pulsed therapy with itraconazole (5 mg/kg orally once daily, two days on/ five days off for three weeks) has been shown to be efficacious in the treatment of Malassezia dermatitis in dogs and thus should be effective as a preventative, although one report highlighted potential for development of antifungal drug resistance with pulse dosing (Section 11.5.2). By contrast, this regimen was not fully effective at reducing otic counts of Malassezia and therefore pulsed dosing cannot currently be recommended for prevention of otitis externa. There are only anecdotal reports of preventative efficacy of itraconazole for dermatitis at a once-weekly interval. Ketoconazole (5–10 mg/kg orally once daily, two consecutive days per week) has also been recommended anecdotally without any published studies at this dose, although itraconazole is generally regarded as being a safer drug (See Section 15).
伊曲康唑的脉冲疗法（5mg/kg，口服每日一次，连用两日，停药5日，持续3周）已经显示对于预防犬马拉色菌皮炎是有效的，但只有一项报告提示了脉冲给药对于药物耐药性的潜在风险（第11.5.2节）。相比之下，仅有传闻报道了ITZ每周一次间隔预防马拉色菌皮炎。KTZ（5–10 mg/kg，口服每日一次，每周连续两天）也被推荐，有趣的是这个剂量下没有任何发表的研究，但伊曲康唑通常被认为是更安全的药物。这个方案对于马拉色菌耳炎使酵母菌计数减少是不完全有效的，因此不推荐脉冲剂量治疗马拉色菌耳炎（见第15节）。
16.4 Malassezia Allergen-Specific Immunotherapy
16.4马拉色菌过敏原-特异性免疫疗法
Hyposensitisation to Malassezia by immunotherapy was initially proposed in 1998 as an alternative to extended or repeated administration of antifungal drugs in dogs with recurrent Malassezia dermatitis with demonstrated IgE to Malassezia antigens. In a non peer-reviewed report on Malassezia immunotherapy (aqueous extract, 1,000 PNU weekly, Greer Laboratories, Lenoir, GA, USA) added to conventional immunotherapy for other allergens in four dogs with atopic dermatitis still prone to recurrent Malassezia dermatitis, results were reported as good to excellent in all cases. A retrospective study reported a good response to subcutaneous alum-precipitated immunotherapy (Artuvetrin100 lg/mL, ArtuVet Animal Health BV, Lelystad, Netherlands) using 1 mL per month (dose adjusted if required based on clinical response) for a minimum of 10 months. Nine of 16 Malassezia monosensitised dogs had an observed reduction in use of both anti-inflammatory and antifungal medication, as well as a >50% reduction in pruritus scores. However, despite the improvement noted in both studies, the quality of evidence remains low and the significance of >50% improvement of pruritus is disputable as a meaningful measure of success. Further studies are required to better assess the potential benefits of Malassezia allergen-specific immunotherapy as a preventative approach.
最初提出通过免疫疗法治疗马拉色菌是在1998年，马拉色菌皮炎的犬中已证实含有对马拉色菌的IgE，该疗法可以作为延长或反复使用抗真菌药物的替代疗法。关于马拉色菌免疫疗法的非同行评审报告中（水提取物，每周1,000 PNU格里尔实验室 美国左治亚州勒努瓦），对4只仍然容易复发马拉色菌皮炎的特应性皮炎犬的其他过敏原加入常规免疫疗法，在所有案例中结果表现为良好。回顾性研究报告对皮下明矾沉淀免疫疗法每月使用1mL持续10个月（可根据临床反应调整剂量）。16只马拉色菌过敏的犬有9只观察到同时减少抗炎药物和抗真菌药物，瘙痒评分下降50%以上；但两项研究均有改善但证据质量仍然很低，改善瘙痒情况>50%仍具有争议。但仍作为一个有意义的措施。需要进一步研究以更好地评估马拉色菌过敏原特异性免疫治疗作为预防方法的潜在益处。
16.5 Conclusions
16.5结论
When predisposing factors cannot be controlled, regular treatment is often required to minimise relapses. Topical treatments are preferred to systemic treatments for longterm therapy because of a lower risk of toxicity. Topical prevention of Malassezia dermatitis in dogs might be achieved using 2% chlorhexidine/2% miconazole or 3% chlorhexidine shampoo twice weekly, as has been previously recommended for treatment. Lesser frequencies may be useful in preventing relapse in some cases but there is currently no evidence to support this. Twice weekly topical hydrocortisone aceponate shows promise in the prevention of Malassezia otitis externa associated with allergic skin diseases. Pulsed therapy with itraconazole (5 mg/kg orally once daily, two days on/ five days off for three weeks) has been shown to be efficacious in the treatment of Malassezia dermatitis (but not otitis externa)in dogs and thus should be effective as a preventative, although one report has highlighted potential for development of antifungal drug resistance with pulse dosing. There are only anecdotal reports of preventative efficacy of itraconazole for dermatitis at a once-weekly interval.
当易感因素无法控制时，定期治疗通常使疾病复发频率降至最小。对于需要长期的皮肤管理，首选外部治疗优于全身性治疗，因为药物毒性最低。如先前的治疗建议对于马拉色皮炎的犬外部预防每周两次使用2％氯己定/ 2％咪康唑或3％氯己定药浴。在某些病例中，较低的频率可能有助于防止复发，但是目前没有证据支持这一点。每周两次外用氢化可的松醋丙酯显示了在预防过敏性皮肤病有关的马拉色菌外耳炎的前景。在犬的马拉色菌皮炎治疗中伊曲康唑脉冲疗法（口服5 mg/kg，口服每日一次，连续2天/停药吧5天，持续三周）已经显示作为预防措施是有效的（非外耳炎）。但一份报告强调了通过脉冲给药产生耐药性的潜力。仅有传闻报道伊曲康唑进行预防性的治疗使用是每周一次。
17 Malassezia yeasts as zoonotic agents
17马拉色菌作为人畜共患病媒介
17.1 Background
17.1背景
Characterizing the zoonotic potential of pathogenic agents is always a difficult task. The concomitant presence of the same species or the same genotypes in humans and animals is a first indication but of course it is not absolute proof unless transmission from one host to another has been clearly demonstrated. The case of Malassezia yeasts is rather complex because many of the 18 currently described species have been found on the
skin of animals as well as of humans (Table 1).
病原体具有人畜共患的潜在致病特征，这始终是一项艰巨的任务。人与动物同时存在相同物种或相同基因型是首次显示，但是当然除非已经证明了从一个宿主到另一宿主的传播，否则它不是绝对的证明。马拉色菌的情况相当复杂，因为在人和动物的皮肤上已经发现了18种不同的亚种（table 1）。
17.2 Skin colonisation in humans
17.2人类皮肤的定植
Several species of Malassezia yeast are known to colonize healthy people as part of the commensal microbiome of human skin. Spatial distributions of the species most commonly identified (M. globosa, M. sympodialis and M. restricta) may vary according to the age, body site and geographical location of the subjects studied. The archetypal zoophilic species, M. pachydermatis, may also be isolated from healthy human skin by culture or detected by molecular techniques, especially from the face and hands. retrospective study of 32 Malassezia spp. isolates from human clinical specimens collected in 1984 at the Center for Disease Control in Atlanta (USA) 15 were identified as M.pachydermatis. These last isolates were mainly from skin, tissue fluids (e.g. eye, ear, vagina) and four were isolated from blood. Skin colonization by Malassezia species in full term healthy newborns has been also investigated. Malassezia pachydermatis was not isolated from the skin of human neonates, while M. sympodialis and M. globosa colonisation begins at birth and increases in the first weeks of life.
目前已知几种马拉色菌均可定植在健康人的皮肤上作为人皮肤常见微生物的组成部分。最常见的物种（球形马拉色菌、合轴马拉色菌、限制性马拉色菌）的空间分布可能会根据所研究对象的年龄，身体部位和地理位置而变化。典型的人畜共患种属为厚皮马拉色菌，还可通过培养或通过分子技术从健康的人类皮肤中分离出来，尤其是从脸部和手部进行检测。1984年美国亚特兰大CDC在32例人临床标本分离株的回顾性研究分离出15株厚皮马拉色菌。最后分离出的这些来自于皮肤、组织液（如眼睛、耳朵、阴道），其中四个来自血液。还对足月健康新生儿进行了马拉色菌属的皮肤定植调查。厚皮马拉色菌不能从人类新生儿中被分离出来，而球形马拉色菌和合轴马拉色菌可以从出生开始到最初的几周逐渐增加。
17.3 Genotyping
17.3基因分型
In epidemiological studies, genotyping of Malassezia yeasts may be required in order to identify the source of infection and to discover possible connection of genotypes with particular diseases. Different studies targeted various RNA or DNA regions in order to distinguish the molecular pattern of M. pachydermatis and to assess whether genotype classification was in accordance with host preferences. In one of these studies, the partial sequencing or large subunit rRNA in one hundred isolates resulted in the differentiation of seven different haplotypes, namely Ia, Ib, Ic, Id, Ie, If, Ig.Haplotypes Ic, Id and Ig seemed to be specific to one animal species (rhinoceros, dogs and ferrets, respectively). Isolates from humans all belonged to haplotype Ia which was also detected in animals (especially dogs and cats). More recently, the spectrum of fungal species (“mycobiome”) in the human skin was investigated using next generation sequence techniques. In this study, 14 skin sites representing a range of physiological characteristics were sampled from 10 healthy adult volunteers. Malassezia yeasts predominated on most of the sampled body sites and 11 Malassezia species (including M. pachydermatis) were directly identified by rRNA gene sequencing from the different clinical samples.
在流行病学研究中，马拉色菌的基因分型可能需要用以确定感染源以及去发现可能的基因型与特定疾病的联系。为了区分厚皮马拉色菌的分子模式以及评估基因型分类是否符合宿主偏好，不同研究针对各个RNA或DNA区域。其中一项研究中，对一百个分离株进行了部分测序或大亚基rRNA导致七种不同单倍型的分化，即Ia、Ib、Ic、Id、Ie、If、Ig。单倍型Ic、Id和Ig似乎分别只特定于一种动物（分别是犀牛、犬、雪貂），人类分离株都属于单倍型Ia，该类型在动物中（特别是犬猫）也可以检出。最近人体皮肤中真菌种类（“菌群”）的谱系使用了下一代序列技术进行了研究；在这个研究中来自10位健康的成人志愿者抽取了代表一系列生理特征的14个皮肤部位。马拉色菌在大多数采样的身体部位成为主要的菌种以及通过rRNA基因测序直接从不同的临床样本中鉴定出11种马拉色菌。
17.4 Isolation of Malassezia pachydermatis from humans
17.4分离自人类的马拉色菌
Pathogenic roles for various Malassezia species have been described in association with several human skin diseases including atopic dermatitis, seborrhoeic dermatitis, folliculitis, psoriasis and pityriasis versicolor. Among these diseases, M. pachydermatis has been most commonly isolated from human patients with seborrheic dermatitis. However, it is difficult to assign a truly pathogenic role to M. pachydermatis in the context of these studies and its identification from surface samples of human skin is typically ascribed to contact with dogs (even though epidemiological data on pet contact is not always available). One exception has been the report of a facial granuloma in a dog owner, where M. pachydermatis was identified by electron microscopy in affected tissues, the yeast was grown and identified by standard microbiological methods and the patient responded to anti-fungal therapy.
Malassezia pachydermatis has also been isolated with significantly higher prevalence from the sputum of asthmatic human patients (21.7%) than from healthy controls (0%). The clinicopathologic significance of this finding, if any, is unknown and data on pet ownership was not collected from the subjects studied.
与人类皮肤疾病有关的致病性马拉色菌已经被报告，包括特应性皮炎、脂溢性皮炎、毛囊炎、银屑病。这些疾病当中患有脂溢性皮炎的患者最常见的是厚皮马拉色菌；这些研究中很难确定厚皮马拉色菌的致病作用，在人皮肤样本中被分离出该菌被认为是由于与犬的接触（尽管并非总是可以获得与宠物接触的流行病学）。其中一个例外是在患面部肉芽肿的犬主受影响组织中通过电子显微镜观察到厚皮马拉色菌。酵母菌的生长通过标准的微生物学鉴定方法且患者对抗真菌治疗有反应。从人哮喘患者的痰液中分离出厚皮马拉色菌的患病率（21.7％）也高于健康组（0%）。发现的临床病理学意义，如果有是未知的以及动物主人的数据没有在研究对象中收集。
17.5 Zoonotic aspects
17.5人畜共患风险
From a zoonotic perspective, the pathogenic role best documented for M. pachydermatis is a syndrome of life-threat-ening fungaemia that occurs in pre-term neonates while receiving lipid-rich nutritional infusions via catheter. Malassezia furfur is the primary skin-colonizing species of human infants and is therefore the species most commonly implicated in this syndrome; however M. pachydermatis has also been clearly documented as an aetiological agent. For example, an epidemiological investigation of an outbreak occurring in a neonatal intensive care unit (NICU) identified a single strain of M. pachydermatis –as determined by pulsed-field gel electrophoresis – which was isolated from 15 infants with sepsis, nine colonized infants, the hands of a nurse and three dogs owned by other health care workers in the NICU. In another study,47 out of 86 M. pachydermatis isolates collected from 25 neonatal patients at a French University Hospital were genotyped using intergenic-spacer 1 nucleotide sequence polymorphisms analysis. All 47 isolates clustered within sequence type 3 (most of them clustered within the 3D subtype, the remaining clustered within three newly described subtypes: 3E, 3F and 3G). No particular subtype was associated with a collection site or a particular time-pe-riod but multiple genotypes could colonize the same neonatal patient. The outbreak resolved upon implementation ofinfection control measures, including withdrawal of lipid-rich hand moisturisers from staff. In addition to this neonatal syndrome, M. pachydermatis has been implicated in severe systemic infections of immunocompromised adult patients.
从人畜共患的角度来看，最能说明厚皮马拉色菌致病作用的是威胁生命的真菌败血症综合征，这种情况发生在早产以及同时接受脂质营养输注的幼儿。糠秕马拉色菌是人类婴儿皮肤的主要定植亚种，因此该综合征常见于该亚种。然而厚皮马拉色菌也被明确记录为该病的病因，如一项针对新生儿重症病房（NICU）流行病学调查确定了单个厚皮马拉色菌菌株，这是通过脉冲场凝胶电泳来确定-是从15名败血症新生儿的9名中分离出来，在护士的手掌以及NICU其他健康护理人员拥有的3只犬中也同样分离出。在另外一项研究通过使用基因间隔区一个核酸序列多态性分析中，法国大学医院从25名新生儿收集了86份样本中有47份分离出厚皮马拉色菌；所有47个分离株均为3型 （其中大多数集中在3D子型，其余三个分别是3E、3F和 3G），没有特定的子型与收集地点或特定时间相关，但多种基因型可以定植在同一名儿童的皮肤上。在实施感染控制措施后得到解决，包括工作人员不再使用富含脂质的护手霜。除这种新生儿综合征，厚皮马拉色菌可能会造成免疫低下的成人严重的全身感染。
In a study designed to estimate the prevalence of M.pachydermatis hand carriage by dog owners, two groups of people were sampled by culture and PCR techniques: owners of 50 healthy dogs and owners of 75 atopic dogs with cytological evidence of Malassezia dermatitis and/or otitis. When detection rates by hand culture were compared, owners of affected dogs were 11 times more likely to be positive for yeast isolation than owners of healthy dogs. However, there was no difference between groups when the highly sensitive PCR technique was utilized, as greater than 90% (70 of 75) of owners in each group had detectable hand carriage. This study served to underscore the importance of good hand hygiene by health care professionals in whom mechanical carriage of many ubiquitous opportunistic pathogens is possible. Very little is known about hand washing agents and techniques (contact time etc.) that will effectively eliminate carriage of Malassezia yeasts from human hands. However, it is known that both chlorhexidine and polyhexanide have excellent in vitro activity against M. pachydermatis. In addition, improved hand-washing practices eliminated an endemic problem with M. pachydermatis infections in a NICU.
一项研究旨在对犬主手掌厚皮马拉色菌的携带的估算中，通过培养和PCR技术对两组人进行样本采集：50只健康犬的主人和75只特应性皮炎犬的主人且伴有马拉色菌皮炎/耳炎的细胞学证据，比较人工培养的检出率，患犬主人的酵母菌阳性率是健康犬主人的11倍，然而使用高灵敏度的PCR时组间没有差异，每个组中可以检出超过90%（70/75）。这项研究强调了病原微生物无处不在，有可能在无意识下成为携带者，所以医护保健专业人员应注意手部卫生。关于手部清洁剂和清洗技巧（清洗时间等）知之甚少，这将有助于从携带者中清除马拉色菌。我们都知道氯己定和聚己缩胍盐酸盐具对厚皮马拉色菌有良好的体外活性。此外在NICU中改进清洁习惯是清除厚皮马拉色菌是普遍性的问题。
17.6 Conclusions
17.6结论
Given the high prevalence of M. pachydermatis hand carriage by dog owners (as assessed by PCR) and the relative rarity of serious human infections by this organism,it may be surmised that the overall risk for zoonosis is quite low, especially among people who are not severely immunocompromised. The need for good hand hygiene by individuals in contact with pet dogs and cats should be emphasised.
由于动物主人的手部普遍携带厚皮马拉色菌（通过PCR评估）以及这种酵母菌对于人类的严重感染是罕见的，所以推测这种疾病对于人畜共患病的总体风险较低，尤其是在免疫系统没有受到严重损害的群体中。应强调与犬猫接触的群体必须保持良好的手部卫生。
Table 3. Clinical trials of oral ketoconazole in the treatment of canine Malassezia dermatitis in dogs and level of evidence (LoE) 犬马拉色菌皮炎口服KTZ临床试验的证据等级（LoE） |
| | | | | | |
| RCT-UB (10 dogs per group) 每组10只犬 | | 7/20 complete response, rest partial 完全反应，不完全反应 | In 10 mg/kg group: vomiting 小组：呕吐 [n = 2], anorexia 厌食 [n = 1], apathy 精神沉郁 [n = 1] | Small group sizes; two KTZ doses compared 小组人数；比较两种KTZ剂量 | |
| RCT-B (seven dogs received KTZ) 7只犬接受KTZ | | 4/7> 50 % clinical Improvement 50%临床改善 | | Small group sizes and concurrent cefalexin therapy limits interpretation. Compared with terbinafine. 小组人数和同时口服头孢氨苄治疗限制了解释。 与特比奈芬相比。 | |
| RCT-B (10 dogs received KTZ) 10只接受KTZ | | 4/10 complete response, 6/10 partial 4/10完全反应，6/10部分反应 | | Small group sizes; compared to pulse ITZ 小组人数；与脉冲ITZ相比 | |
| | | 83% Improvement at six weeks 83%六周改善 | | Abstract publication only; compared to shampoo alone or combined with KTZ 仅以摘要发表；与单独使用香波相比或同时口服KTZ | |
| RCT-B (12 dogs received KTZ + cefalexin) 12只犬接受KTZ和头孢氨苄 | | 7/12 > 50 %clinical improvement 7/12> 50％的临床改善 | 6/12 dogs: Transien短暂的t Anorexia厌食 [n = 2], Vomiting呕吐 [n = 3], vomiting and soft stool呕吐和软便 [n = 1] | Concurrent cefalexin therapy limits interpretation. Compared with FCZ. 与FC相比，同时口服头孢氨苄限制了解释 | |
FCZ fluconazole, 氟康唑ITZ itraconazole,伊曲康唑 KTZ ketoconazole, 酮康唑RCT-B randomized controlled trial – blinded,随机对照试验（盲法） RCT-UB randomized controlled trial – unblinded.随机对照试验（无盲） |
Table 4. Clinical trials of oral itraconazole in the treatment of canine Malassezia dermatitis and level of evidence (LoE)口服ITZ治疗犬马拉色菌皮炎的临床试验的证据等级（LoE）
| | | | | | |
|
| RCT-B (10 dogs per group) 随机对照盲法，每组10只 | 5 mg/kg once daily or two consecutive days/week, for21 days 5mg/kg/bid或每周连续两天，至21天 | Median lesion score reduced by 60% (pulse) and 31% (daily) | | Small group sizes; two ITZ intervals compared 小组人数；比较两个ITZ间隔疗效 | |
|
| RCT-BNS (11dogs received ITZ) RCT未标明盲法，11只接受ITZ | | All responded fully by d22 | | Combined with twice weekly selenium sulphide shampoo. No statistical Analyses 每周两次硫化硒香波，没有统计分析 | |
|
| RCT-B (10 dogs received ITZ) 10只犬接受ITZ | 5 mg/kg once daily for two consecutive days/week 每周连续两次 | 5/10 complete response, 5/10 partial 5/10的完全反应和5/10的部分反应 | Transient vomiting [n = 2],短暂的呕吐 inappetence [n = 1]食欲不振 | Small group sizes; compared with KTZ 小组人数；与KTZ相比 | |
|
ITZ itraconazole,伊曲康唑 KTZ ketoconazole, 酮康唑RCT-B randomized controlled trial – blinded,随机对照试验（盲法）RCT-BNS randomised controlled trial – blinding not specified. 随机对照试验–未标明盲法 |
Table 5. Clinical trials of oral fluconazole and terbinafine in the treatment of canine Malassezia dermatitis with level of evidence (LoE)
Table 5.口服FCZ和特比奈芬治疗犬马拉色菌皮炎临床试验证据等级(LoE)
| | | | | | | |
| | RCT-B (13 dogs received FCZ + cefalexin) 13只犬接受FCZ+头孢氨苄 | | 8/13> 50 % clinical improvement >50％的临床改善 | 6/13 dogs: 6只犬出现了症状 Transient vomiting [n = 4], 短暂性呕吐 vomiting and soft stool [n = 1], 呕吐和软便 diarrhoea [n = 1] 腹泻 | Concurrent cefalexin Limits interpretation. Compared with KTZ + cefalexin. 并存的头孢氨苄限制了解释。 与KTZ+头孢氨苄相比。 | |
| | RCT-B (8 dogs received terbinafine +cefalexin) 8只犬接受特比奈芬+头孢氨苄 | | 3/8 > 50 % clinical improvement >50％的临床改善 | | Small group sizes and concurrent cefalexin limits interpretation. Compared with KTZ + cefalexin. 小组人数；并存的头孢氨苄限制了解释。 与KTZ+头孢氨苄相比。 | |
| | RCT-B (10 dogs Received terbinafine at either dose) 10只犬接受两种剂量 | 30 mg/kg once daily OR on two consecutive days/week, for 21 days 一日一次或每周连续两次给与21天 | 8/10> 50% clinical improvement in both groups 两组中8/10> 50％的临床改善 | Mild signs in 3/10 dogs in both groups 两组中3/10的犬出现轻微症状 (overall 6/20); （总数6/20） vomiting [n = 2], 呕吐 diarrhoea [n = 2], 腹泻 anorexia [n = 1], 厌食 panting [n = 1]. 气喘 Elevated ALT in 1 dog.1只犬ALT升高 | Small group sizes. Complete clinical resolution in only 3/20 dogs at d21. Eight dogs developed pyoderma. 小组人数；第21天时只有3/20完全解决，八只犬患了脓皮病 | |
ALT alanine aminotransferase,丙氨酸氨基转移酶 KTZ ketoconazole,酮康唑 RCT-B randomised controlled trial – blinded. 随机对照试验（盲法） |
Table 6. Clinical trials of 2% miconazole/ 2% chlorhexidine and 3% chlorhexidine shampoos in the treatment of canine Malassezia dermatitis with level of evidence (LoE)
Table 6.2％咪康唑/ 2％氯己定和3％氯己定香波治疗犬马拉色菌皮炎临床试验证据等级（LoE）
| | | | | | | LoE 等级 |
| 2% miconazole 2%chlorhexidine 2%咪康唑 2%氯己定 | RCT-B (16 basset hounds received MC-CH) 16只巴吉度犬接受MC-CH | | 15/16 “marked improvement” 明显改善 | | Compared to 0.25%selenium Sulphide shampoo 与0.25％硫化硒香波比较 | |
| 2% miconazole 2%chlorhexidine 2%咪康唑 2%氯己定 | RCT-B (32 dogs received MC-CH) 32只犬接受MC-CH | | Good (≥50%) response in 91% of dogs 良好（≥50%），91%的犬有反应 | | | |
| 2% miconazole 2%chlorhexidine 2%咪康唑 2%氯己定 | | | 85% improvement at 6 weeks 85%在六周时改善 | | Abstract publication only 仅摘要发表 | |
| | RCT-B (22 dogs received CH) 22只犬接受CH | Thrice weekly for 2 weeks, then twice weekly for two weeks, then weekly if needed 前两周每周三次，之后两周每周两次，然后根据需要一周一次 | Good (≥50%) response in 86% of dogs 良好（≥50%） 86%的犬有反应 | Transient self- limiting pododermatitis [n = 1], increased pruritus [n = 2], exfoliation [n = 2] | | |
CH 3% chlorhexidine, 3%氯己定MC-CH 2% miconazole/2% chlorhexidine, 咪康唑和氯己定RCT-B randomised controlled trial – blinded.随机对照试验-盲法 |
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发表于 2022-5-7 16:11:32
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