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西伯利亚哈士奇锌反应性皮肤病变 作者：Andrew Rosenberg, DVM, DACVD Animal Dermatology Allergy Specialists Riverdale, New Jersey White Plains, New York 翻译：刘双元 校对：赵博
Trooper, a 3-year-old 67-lb (30.5-kg) intact male Siberian husky, was presented to the dermatology clinic for skin lesions around the eyes. Lesions were first appreciated ≈4 months prior to presentation and showed no response to amoxicillin/ clavulanic acid or cefpodoxime, which were prescribed by the primary veterinarian. Treatment with combined trimeprazine/prednisolone twice daily and tapered over 1 month resulted in partial improvement. The affected areas were only mildly pruritic. According to the owner, the lesions around the eyes had worsened, and the scrotum had become inflamed in the previous 4 months. Trooper，一只3岁67 lb（30.5公斤）未去势的雄性西伯利亚哈士奇，因眼周皮肤病变到皮肤科门诊就诊。就诊前约4个月首次发现病变，对首诊兽医开出的阿莫西林克拉维酸或头孢泊肟无反应。联合异丁嗪/泼尼松龙每日2次治疗，并在1个月后逐渐减量后，部分改善。患处仅有轻度瘙痒。据主人介绍，眼周病变加重，且近4个月开始阴囊炎。
Physical Examination 体格检查 On examination, Trooper was bright, alert, and responsive. All peripheral lymph nodes were normal. Periocular regions were alopecic with mild to moderate crusting (Figure, next page). The pinnae were moderately erythematous on the concave surface with mild adherent scaling. The scrotum was severely erythematous. All paw pads were crusted. The remainder of the examination was unremarkable. Trooper精神抖擞，警觉机敏，反应灵敏。所有外周淋巴结均正常。眼周区域脱毛伴轻度至中度结痂（图，下页）。耳廓凹面中度红斑，有轻度粘附鳞屑。阴囊严重红斑。所有爪垫均结痂。其余检查未见异常。
FIGURE Affected areas showing alopecia (A), crusting (B), and scaling (C) 图 受累区域显示脱毛(A)、结痂(B)和皮屑(C)
Diagnosis 诊断 Evaluation of an impression smear of the periocular region revealed numerous cocci with streaming neutrophils. A deep skin scrape was negative for ectoparasites. Skin biopsies were discussed with Trooper’s owner; however, superficial pyoderma was initially treated prior to biopsy to ensure accurate results. Bacterial culture and susceptibility testing was performed on the lesions to guide therapy 眼周区域染压片染色的诊断评估可见大量球菌伴中性粒细胞染色质。皮肤深刮片未见外寄生虫。与Trooper主人讨论了皮肤活检；在活检前先治疗浅表脓皮病，以确保活检结果的准确。对病灶进行细菌培养和药敏试验，指导治疗
Four days after initial presentation, culture results revealed methicillin-resistant Staphylococcus schleiferi (Table). Treatment with chloramphenicol (40 mg/kg every 8 hours) was initiated. In addition, the owner was instructed to bathe Trooper weekly using a 3% chlorhexidine/phytosphingosine shampoo. Due to the location of the periocular lesions, topical therapy did not seem appropriate as the sole means of eliminating pyoderma. 初诊后4天，培养结果显示耐甲氧西林施氏葡萄球菌（表）。开始氯霉素（40 mg/kg，每8小时一次）治疗。此外，指导主人每周使用3%氯己定/植物鞘氨醇香波给Trooper洗澡。由于眼周病变的位置，外部治疗似乎不适合作为消除脓皮病的唯一方法。
表 厌氧培养&药敏结果 施氏葡萄球菌4+细菌生长 *S schleiferi is resistant to oxacillin and therefore is methicillin-resistant. All staphylococci are screened for methicillin resistance. *施氏葡萄球菌对苯唑西林耐药，因此对甲氧西林耐药。对所有葡萄球菌进行甲氧西林耐药性筛查。 +Oxacillin can be used to predict methicillin sensitivity. Oxacillin-resistant staphylococci are resistant to all cephalosporins, including cefpodoxime and cefovecin. +苯唑西林可用于预测甲氧西林敏感性。耐苯唑西林葡萄球菌对所有头孢菌素均耐药，包括头孢泊肟和头孢维星。
Infection had improved significantly 2 weeks after initial presentation, and Trooper was returned to the clinic for punch biopsies (6 mm) of the affected areas, performed while he was under sedation. The specimens were submitted for histopathology, which confirmed zinc-responsive dermatosis (see Histopathology Results of Punch Biopsies Indicating Marked Parakeratotic Hyperkeratosis). 初诊2周后感染明显改善，Trooper返回诊所在镇静状态下对患处进行钻孔活检(6 mm)，提交标本进行组织病理学检查，证实为锌反应性皮肤病（见打孔活检组织病理学结果可见明显的角化不全性角化过度）。
HISTOPATHOLOGY RESULTS OF PUNCH BIOPSIES INDICATING MARKED PARAKERATOTIC HYPERKERATOSIS 打孔活检的组织病理学结果可见显著的角化不全性角化过度 Three specimens of haired skin obtained via punch biopsy were evaluated histologically. In all biopsy samples, marked parakeratotic hyperkeratosis that expanded to the follicular infundibula and into the intrafollicular stratum corneum was apparent. The epidermis was moderately spongiotic, and mild acanthosis and leukocyte exocytosis were observed. The superficial dermis was markedly expanded by edema and a mild interstitial chronic inflammatory infiltrate of small lymphocytes, plasma cells, and fewer granulocytes. Many superficial dermal fibroblasts were plump and reactive; this type of superficial dermal expansion can give the skin surface a papillated appearance. Multifocal small inflammatory aggregates associated with adnexa were observed in 2 sections throughout the dermis; these inflammatory cells included epithelioid macrophages, lymphocytes, plasma cells, and neutrophils. Free keratin (ie, furunculosis) was observed in one of these foci. 对3处打孔活检获得的皮肤毛发样本进行组织学评估。所有活检样本中都可见明显的角化不全性角化过度，扩展到毛囊漏斗部并进入毛囊内角质层。表皮中度棘层水肿，可见轻度棘层肥厚和白细胞胞吐。由于水肿和轻度间质慢性炎症浸润，真皮浅层明显扩张，小淋巴细胞、浆细胞和少量粒细胞浸润。许多浅表真皮成纤维细胞丰满，反应性强；这种类型的浅表真皮扩张可使皮肤表面呈现乳头样外观。在贯穿真皮的2张切片中观察到与附件相关的多灶性小炎性聚集物；这些炎性细胞包括上皮样巨噬细胞、淋巴细胞、浆细胞和中性粒细胞。在其中一个病灶中观察到游离角质（即疖病）。 Hyperkeratosis, especially of the superficial follicular infundibula, was striking and suggestive of zinc-responsive dermatosis. The superficial dermal edema and foci of furunculosis were suggestive of resolving pyoderma. 角化过度，尤其是浅表毛囊漏斗角化过度，是锌反应性皮肤病的显著表现。皮肤浅表水肿及疖病病灶提示脓皮病有所缓解。
Staphylococcus schleiferi is resistant to oxacillin and therefore is methicillin-resistant. 施氏葡萄球菌对苯唑西林耐药，因此对甲氧西林耐药。 TREATMENT AT A GLANCE 治疗浏览 Cytologic impression smears should be performed and any secondary infections (eg, Malassezia pachydermatis, bacteria) treated. 应进行细胞学压片，并对任何继发性感染进行治疗（如厚皮马拉色菌、细菌）。 Zinc-responsive dermatosis syndrome I should be treated through long-term supplementation with zinc sulfate, zinc gluconate, or zinc methionine, and doses should be based on elemental zinc (initial dose, 2-3 mg/kg once daily or split and given every 12 hours). Zinc sulfate may have lower bioavailability and can cause gastric irritation. I型锌反应性皮肤病综合征应通过长期补充硫酸锌、葡萄糖酸锌或蛋氨酸锌进行治疗，剂量应以锌元素为基础（初始剂量，2-3 mg/kg每日一次或分次给药，每12小时给药一次）。硫酸锌的生物利用度可能较低，可引起胃刺激。
Supplemental therapies (eg, omega fatty acids, corticosteroids, antibacterial topical medications) may be helpful and can be used as warranted. 补充治疗（如ω脂肪酸、皮质类固醇、抗菌外用药物）可能有帮助，可根据需要使用。 Low-dose corticosteroids can be beneficial for treatment of dogs that do not respond to zinc alone,as corticosteroids are known to increase zinc absorption from the GI tract. 低剂量的皮质类固醇对单独锌治疗无反应的犬是有益的，因为皮质类固醇被认为可以增加胃肠道的锌吸收。
DIAGNOSIS 诊断 ZINC-RESPONSIVE DERMATOSIS SYNDROME I I型锌反应性皮肤病综合征 Treatment & Long-Term Management 治疗和长期管理 Chloramphenicol therapy was continued for 4 weeks, including 1 week after resolution of clinical signs of infection and cytologic cure. Supplementation with zinc methionine (elemental zinc, 3 mg/kg once daily [dose can be split and given every 12 hours]) was initiated (see Treatment at a Glance). 氯霉素治疗持续4周，包括感染临床症状的消退和细胞学治愈的一周后。开始补充蛋氨酸锌（元素锌，3 mg/kg，每日一次[剂量可分次给药，每12小时给药一次]）（见治疗一览）。
Trooper was rechecked 1 month after zinc therapy was initiated; lesions showed some improvement, and evaluation of an impression smear confirmed the absence of bacteria. Low-dose methylprednisolone (initial dose, 0.7 mg/kg once daily) was initiated and tapered over 1 month. In many cases, low-dose corticosteroids can be beneficial for treatment of dogs that do not respond to zinc alone, as corticosteroids are known to increase zinc absorption from the GI tract. Trooper在锌治疗1个月后复查，可见病变有一些改善，压片评估证实无菌。开始使用低剂量甲强龙（初始剂量，0.7 mg/kg，每日一次），并在1个月内逐渐减量。许多情况下，低剂量皮质类固醇对单独锌治疗无反应的犬可能有益，因为已知皮质类固醇可增加胃肠道对锌的吸收。
Prognosis & Outcome 预后和结果 Trooper was presented 6 weeks later for a recheck examination. He had not received methylprednisolone for 2 weeks, and all lesions were resolved. Zinc methionine supplementation was continued, and Trooper was free of lesions. Lifelong zinc supplementation is typically needed. Long-term prognosis is favorable as long as zinc supplementation is maintained. 6周后，Trooper接受复查。2周未接受甲强龙治疗，所有病变均消退。继续补充蛋氨酸锌，Trooper无病变。通常需要终身补锌。只要保持补锌，长期预后是良好的。
Discussion 讨论 Zinc-responsive dermatosis syndrome I is a condition that occurs primarily in Alaskan malamutes, Siberian huskies, and other arctic breeds and may be associated with defective intestinal absorption of zinc. I型锌反应性皮肤病综合征是一种主要发生于阿拉斯加雪橇犬、西伯利亚哈士奇和其他北极品种的病症，可能与肠道对锌的吸收缺陷有关。 Syndrome II occurs in dogs fed a zinc-deficient diet. The author has anecdotally seen an increase in the number of syndrome II cases that may be a result of an increase in dogs being fed home-prepared and alternative diets. Lesions are typically located at mucocutaneous junctions and paw pads and appear as areas of erythema with scaling, crusts, and hyperkeratosis. II型综合征发生在饲喂锌不足饮食的犬中。作者看到非正式记录中Ⅱ型综合征病例数增加，这可能是饲喂自制食物和替代饮食的犬增加的结果。病变通常位于皮肤粘膜结合处与爪垫，表现为红斑伴皮屑、结痂和角化过度。 Zinc-responsive dermatosis should be on the differential diagnosis list for crusted skin disease in any northern- or arctic-breed dog (see Take-Home Messages). Diagnosis is made through history and biopsy. Serum or hair levels of zinc may be low in affected patients; however, proper analysis can be difficult due to a variety of factors, so biopsy is the recommended diagnostic test if zinc-responsive dermatosis is suspected. 锌反应性皮肤病应列入任何北方或北极犬种的结痂性皮肤病的鉴别诊断列表中（见关键信息）。通过病史和活检进行诊断。患犬血清或毛发的锌水平可能较低；但由于多种因素很难进行适当的分析，因此如果怀疑锌反应性皮肤病，推荐的诊断试验是活检。
Take-Home Messages 关键信息 There are 2 types of zinc-responsive dermatosis: syndrome I, which affects arctic breeds (most frequently Siberian huskies and Alaskan malamutes) and appears to be associated with abnormal intestinal absorption of zinc, and syndrome II, which may affect dogs fed a zinc-deficient diet. 有2种类型的锌反应性皮肤病：I型综合征，涉及北极品种（最常见的是西伯利亚哈士奇和阿拉斯加雪橇犬），似乎与肠道对锌的异常吸收有关；II型综合征，可能涉及饲喂锌缺乏饮食的犬。
Diagnosis is made via history and biopsy. 通过病史和活检进行诊断。
Syndrome I should be treated with zinc supplementation. Doses should be based on elemental zinc (initial dose, 2-3 mg/kg once daily or split and given every 12 hours). Ⅰ型综合征应补锌治疗。剂量应根据元素锌（初始剂量，2-3 mg/kg，每日一次或分次给药，每12小时一次）。
Corticosteroids can be helpful for dogs with syndrome I that do not respond to zinc supplementation alone. Omega fatty acids may also be helpful. 对于单独补锌治疗无效的I型综合征患犬，皮质类固醇可能有帮助。ω脂肪酸也可能有帮助。
Once identified and treated, the prognosis for both syndromes is typically favorable. 一旦确定并治疗，两种综合征的预后通常良好。
References 参考文献 1. Miller W, Griffin C, Campbell K. Nutrition and skin disease. In: Miller W, Griffin C, Campbell K. Muller and Kirk’s Small Animal Dermatology. 7th ed. St. Louis, MO: Elsevier; 2013:689-691. 2.White SD, Bourdeau P, Rosychuk RA, et al. Zinc-responsive dermatosis in dogs: 41 cases and literature review. Vet Dermatol. 2001;12(2):101-109. 3.Roudebush P, Wedekind KJ. Zinc-responsive dermatosis in dogs. Vet Dermatol. 2002;13(1):63. 4. Burton G, Mason KV. The possible role of prednisolone in “zincresponsive dermatosis” in the Siberian husky. Aust Vet Pract. 1998; 28(1):20-24. 5.Brown RG, Hoag GN, Smart ME, Mitchell LH. Alaskan malamute chondrodysplasia. V. Decreased gut zinc absorption. Growth. 1978;42(1):1-6. 6.Sousa CA, Stannard AA, Ihrke PJ, Reinke SI, Schmeitzel LP. Dermatosis associated with feeding generic dog food: 13 cases (1981-1982). J Am Vet Med Assoc. 1988;192(5):676-680. 7.Logas D, Kunkle GA, McDowell L. Comparison of serum zinc levels in healthy, systemically ill and dermatologically diseased dogs. Vet Dermatol. 1993;4(2):61-64.
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