犬皮肤红斑狼疮：一项综合性评估（6）-盘状红斑狼疮

王帆

Cutaneous lupus erythematosus in dogs: a comprehensive review
犬皮肤红斑狼疮：一项综合性评估
作者：Thierry Olivry , Keith E. Linder and Frane Banovic

翻译：辛蕾 校对：王帆



Discoid lupus erythematosus
盘状红斑狼疮
Historical perspective Among the several variants of human chronic CLE (e.g. discoid LE [DLE], verrucous （hyperkeratotic) LE, chilblain LE, lupus tumidus and lupus profundus), DLE represents the most common form: it is divided into a localized variant where skin lesions are confined to the head and neck, and a generalized form, in which skin lesions also occur below the neck .
历史背景 在人类慢性皮肤红斑狼疮的几种变异型中（如：盘状红斑狼疮DLE、疣状（角化过度）红斑狼疮、冻疮型红斑狼疮、肿胀性狼疮和深部狼疮），盘状红斑狼疮是最常见的：它是一种局部病变的变异型，皮肤病变限于头部和颈部，是一种广义的形式，皮肤病变也会出现在颈部以下。
  
In 1979, Griffin and colleagues reported clinical, histopathological and immunological characteristics of two dogs with localized facial lesions that were diagnosed as being affected with the canine counterpart of human DLE. In these two dogs, the nasal-predominant dermatitis was associated with microscopic focal interface dermatitis, basement membrane thickening and a superficial lymphocytic and plasmacytic dermatitis. Since then, there were three large case series describing dogs with nasal skin-predominant DLE lesions , two of them including some of the same cases. The then-proposed terminology resulted in the widespread acceptance of “canine DLE” being equated mainly to facial localized lesions. In the 2010s, we began reporting dogs with a more widespread phenotype that resembled that of the generalized variant of human DLE; this was followed with the publication of a case series of ten dogs with generalized DLE (GDLE), this article encompassing the three cases already published by the NC State Dermatology group.
在1979年，Griffin和他的同事报道了两只具有局部面部病变犬的临床、组织病理学和免疫学特征，这些犬诊断为与人类盘状红斑狼疮类似。这两只犬中，与鼻部皮炎为主的相关显微镜下表现为局灶性界面性皮炎、基底膜增厚和浅表性淋巴细胞及浆细胞皮炎有关。此后，有三大病例报告里描述了主要是鼻部皮肤病变的犬盘状红斑狼疮，其中两份报告中包含了一些相同的病例。当时提出的术语导致普便认为“犬盘状红斑狼疮”仅会出现面部局部的病变。在21世纪10年代，我们开始报道在犬上更为广泛的类型，类似于人类盘状红斑狼疮的全身型变异型；随后发表了患全身型盘状红斑狼疮（GDLE）的十只犬的一个病例报告，这篇文章涵盖了北卡罗莱纳州立大学皮肤病小组已发表的三个病例。


Signalment The four largest series of dogs with the “classic” localized facial-predominant DLE (FDLE) allows the analysis of a cohort of 104 dogs. Among these cases, there were 32 German shepherd dogs and their crosses (31%). The age of onset of FDLE skin lesions varied between 1 and 12 years of age (median: 7 years);while the female-to-male ratio was 0.7, there was an equal representation of intact and neutered individuals.
特征 在四个最大的犬“经典”局灶、面部盘状红斑狼疮病例报告里，分析了104只犬。在这些病例中有32只德国牧羊犬及其杂交犬（31%）。面部型盘状红斑狼疮皮肤病变的发病年龄在1岁至12岁间（中位年龄7岁）；雌雄比例为0.7，绝育与未绝育的比例相当。
  
A retrospective study recently evaluated the historical and outcome information in ten dogs with GDLE.Amongst these dogs, there were two Chinese crested dogs and two Labrador retrievers; there was one each of the following pure breeds: miniature pinscher, Leonberger, Shih-Tzu and toy poodle. The age of onset of GDLE skin lesions varied between 5 and 12 years of age (median 9 years). The female-to-male ratio was 1.0 and all dogs were castrated. Interestingly—and surprisingly—German shepherd dogs, a breed predisposed to develop several forms of LE, such as SLE, localized FDLE and MCLE, did not seem affected by GDLE. This discrepancy may be explained by the German shepherd breed not being predisposed to this disease, by the small size of the reported cohort or by a possible clinical misdiagnosis of GDLE as one of the” idiopathic lichenoid dermatoses” as they were diagnosed in the 1980’s solely based on the histopathological identification of a “lichenoid tissue reaction” in dogs.
最近一项回顾性研究评估了十只患有全身型盘状红斑狼疮的犬的病史和预后。在这些犬中，有两只中国冠毛犬和两只拉布拉多犬；纯种迷你杜宾犬、兰波格犬、西施犬和玩具贵宾犬各一只。全身型盘状红斑狼疮的发病年龄在5岁至12岁间（中位年龄是9岁）。雌雄比例是1.0，所有犬均已绝育。饶有趣味又出人意料的是德国牧羊犬易患几种类型的红斑狼疮，如系统性红斑狼疮、局部面部型盘状红斑狼疮和黏膜皮肤红斑狼疮，但似乎未患全身型盘状红斑狼疮。这种不一致的原因可能是德国牧羊犬不易患这种疾病,报道的群体规模小或可能临床误诊全身型盘状红斑狼疮为“特发性苔藓样变皮肤病”，在20世纪80年代在犬中仅仅基于组织病理学“苔藓样变组织反应”来诊断。

Incidence and prevalence At this time, there is no usable information to determine the frequency of occurrence of FDLE and GDLE in dogs.
发病率和流行率 目前没有可靠的信息在犬中面部型盘状红斑狼疮和全身型盘状红斑狼疮的发病率和流行率。

Clinical signs The classic skin lesions of human DLE usually consist of early erythematous and variably scaly macules or papules that slowly evolve into a coin-shaped (i.e. discoid), plaques with adherent scales, follicular plugging (i.e. comedones) and peripheral hyperpigmentation presumed to occur secondarily to inflammation. These discoid plaques can coalesce and develop central scarring and depigmentation. Atypical presentations of GDLE have been reported in patients of differing ethnic groups; the morphological appearance of lesions in these patients varies from hyperpigmented macules to hyperkeratotic, hyperpigmented plaques with an erythematous border.
临床症状 人类盘状红斑狼疮的典型皮肤病变通常早期是红斑和各样的鳞状斑点或丘疹，慢慢演变成一个硬币形状（即盘状）、有粘附性皮屑的斑块、毛囊堵塞（即粉刺）和可能继发于炎症的外周色素沉着。这些盘状斑块可合并后发展为中央瘢痕和色素减退。已报道了在不同种族中病患全身型盘状红斑狼疮的非典型表现；这些病患病变的形态外观从色素沉着的斑点到过度角化、具有红斑边缘的色素沉着的斑块。
  
The early skin lesions in canine FDLE consist of erythema, depigmentation and scaling that progress into erosions and ulcerations with atrophy and loss of the architecture of the nasal planum (Fig. 9a-f); crusting may be present if the epithelial integrity is damaged. Skin lesions usually affect the nasal planum (Fig. 9a-f) and might even involve the nares (Fig. 9c,d,f); several dogs exhibit additional skin lesions on the dorso-proximal muzzle (Fig. 9a,b), lips, periorbital skin and pinnae. Squamous cell carcinoma was reported to develop from chronic DLE nasal lesions in dogs , as in humans. Pruritus has been reported to be variable in dogs with FDLE.
犬面部型盘状红斑狼疮的早期皮肤病变是红斑、色素沉着和皮屑，进一步发展为糜烂和溃疡，伴随着鼻平面结构的萎缩和缺失（图9a-f）；如果上皮完整性受损，可能会出现结痂。皮肤病变通常会出现在鼻平面（图9a-f），甚至可能涉及鼻孔附近（图9c、d、f）；有几只犬口鼻背部近端（图9a、b）、唇部、眶周皮肤和耳廓出现了额外的皮肤病变。报道说鳞状细胞癌是由犬慢性盘状红斑狼疮的鼻部病变发展而来，跟人类一样。在犬面部型盘状红斑狼疮中瘙痒情况不确定。
  
Clinicians should remember that cutaneous (epitheliotropic) T-cell lymphomas can have localized lesions that affect the nose and could mimic those of FDLE. Other differential diagnosis for depigmentation and inflammation on the nasal planum are MCP and the uveodermatological syndrome, which resembles the Vogt-KoyanagiHarada syndrome of humans. One should keep in mind that the "so-called MCP" is a poorly described disease that, if it were to even exist as a primary disease, is likely to occur secondarily to other diseases such as FDLE, MMP and MCLE and other nasal-targeting autoimmune and immune-mediated diseases.
临床医生应该记住皮肤（趋上皮性）T细胞淋巴瘤可能有鼻部的局部病变，并且跟面部型盘状红斑狼疮很像。对于鼻平面色素减退和炎症的其他鉴别诊断是黏膜皮肤脓皮病（MCP）和葡萄膜皮肤病综合征，类似于人类的“Vogt-小柳原田综合征”。“所谓的黏膜皮肤脓皮病”并不好描述，当它作为主要疾病时可能继发于其他疾病，如面部型盘状红斑狼疮、黏膜类天疱疮和黏膜皮肤红斑狼疮以及其他以鼻部为靶向病变的自身免疫和免疫介导性疾病。
  
Dogs with GDLE present with generalized or multifocal, annular (discoid) to polycyclic plaques with dyspigmentation, an erythematous margin, adherent scaling, follicular plugging and central alopecia; these predominate on the neck, dorsum and lateral thorax (Fig. 10a,f) . In many of these dogs, the plaques evolved into ulcerations healing with a central atrophic or hypertrophic scar and dyspigmentation(depigmentation and hyperpigmentation) (Fig. 10a,f). Four of ten of the reported dogs (40%) had mucocutaneous regions involved with plaques usually appearing on or around the genitalia. An unusual pattern of reticulated (net-like) hyperpigmentation was visible on the ventral abdomen and lateral thorax in two of these cases, a feature also seen in other CCLE variants such as MCLE. In the largest series of cases, systemic signs were not reported; pruritus and pain at the site of lesions were observed in four (40%) and three of ten dogs (30%), respectively. There are only two canine skin diseases that could closely mimic GDLE: generalized (and often vaccine-induced) ischemic dermatopathies and the very rare hyperkeratotic EM (a.k.a. “old dog” EM).
患有全身型盘状红斑狼疮的犬病变呈全身或多灶性、环状（盘状）到多环斑块伴随着色素沉着异常、边缘红斑、粘附性皮屑、毛囊堵塞和中央脱毛；主要分布在颈部、背部和胸部外侧（图10a、f）。在许多犬中，斑块发展为溃疡，愈合后伴随着中央萎缩或增生性瘢痕和色素沉着异常（色素减退和色素沉着）（图10a、f）。在十只被报道的犬中有四只（40%）有斑块性的黏膜病变，通常出现在生殖器上或其周围。在两例病例中，腹侧和胸部外侧可见一种不寻常的网状色素沉着，这一特征也见于其他慢性皮肤红斑狼疮变异型，如黏膜皮肤红斑狼疮。在最大的病例报告里，全身性症状尚未报道；十只犬有四只（40%）出现病变部位瘙痒，有三只（30%）出现病变部位疼痛。仅有两只犬的皮肤病极像全身型盘状红斑狼疮：全身型（通常由疫苗引起）缺血性皮肤病和角化过度型多形红斑（亦称“老年犬”多形红斑）。


Laboratory evaluation In humans affected with the generalized variant of GDLE, a positive ANA titer is frequently found, and it represents a risk factor for development of SLE within five years after the initial diagnosis of skin lesions. So far, out of the 104 dogs with classic FDLE included in the four largest series of cases, there were no reports of progression to SLE . Seven dogs with GDLE had a low positive ANA serum titer, but a progression with acquisition of additional criteria for SLE was not seen in any dog within the median follow up of 2.5 years (ranging 0.5 to 6 years) in the published series.To our knowledge, the progression of a DLE variant to“clinical” SLE has been reported only in one dog.
实验室检查 在患有全身型盘状红斑狼疮泛发性变异型的人上，常发现阳性的抗核抗体滴度，它代表了最初诊断皮肤病变的五年内系统性红斑狼疮发展的危险因素。目前为止，自四个最大病例报告的104只患有经典性面部型盘状红斑狼疮后，没有系统性红斑狼疮进展的报道。七只患有全身型盘状红斑狼疮的犬具有较低的阳性抗核抗体血清滴度，但在出版的报告里随访的中位年龄为2.5岁（范围0.5岁至6岁）的所有犬中都没有取得系统性红斑狼疮额外标准的进展。据我们所知，盘状红斑狼疮变异型向“临床”系统性红斑狼疮的进展仅在一只犬中有报道。

Histopathology The histology of DLE in dogs is similar to that of humans and is characterized by a lichenoid cell-rich,lymphocytic interface dermatitis reaction pattern with basal keratinocyte vacuolar degeneration, apoptosis, loss of basal cells and basement membrane thickening.
组织病理学 犬盘状红斑狼疮的组织学与人类的相似，其特征是富含细胞的苔藓样变淋巴细胞界面性皮炎，伴随着基底角质细胞空泡变性、凋亡、基底细胞丢失和基底膜增厚。
  
In canine FDLE, the interface reaction (vacuolar degeneration, apoptosis and loss of basal cells) is often subtle or mild in biopsy samples (Fig. 11a-c). Only small areas might exhibit an active interface reaction and these lesions are easily missed, as nasal planum biopsies tend to be few and small. Interface changes can involve the follicular infundibula (Fig. 11d), when lesions extend off of the nasal planum; however, folliculitis has not been specifically investigated in canine FDLE. Pigmentary incontinence occurs secondarily to the interface reaction (Fig. 11a,b) but it is not specific to this type of injury and it can be found, persistent, in the nasal planum of dogs without concurrent nasal dermatitis .Thickening of the basement membrane zone is patchy or multifocal but is not specific,as it occurs with other chronic inflammatory disorders of the nasal planum, such as leishmaniosis, where geographically relevant .Superficial dermal fibrosis can be absent or range from mild-to-marked. Secondary bacterial colonization is common in FDLE and often complicates the histological diagnosis. These issues are compounded by the fact that, historically, the diagnosis of nasal-predominant“canine DLE” was given to dogs when microscopic examination of nasal planum skin biopsy specimens revealed a superficial dermal “band-like” pattern of inflammation rich in lymphocytes and plasma cells (a so-called “lichenoid infiltrate”), without any emphasis on the presence of an interface reaction. In fact, it is now believed that such“lichenoid” lymphocyte and plasma cell rich inflammation is a nonspecific inflammatory pattern seen in and near mucosae or related tissues (oral cavity, nasal planum, eyelids,genitalia, etc.). In a retrospective histological study of nasal dermatitis in dogs, a cell-rich lichenoid infiltrate was common, but only a small subset of subjects with nasal lesions exhibited the interface dermatitis associated with CLE.
在犬面部型盘状红斑狼疮中，活检样本中界面性反应（空泡变性、凋亡和基底细胞丢失）往往是细微的（图11a-c）。只有小面积可能表现出活跃的界面性反应，且这些病变很容易被错过，因为鼻平面的活检面微乎其微。当病变延伸到鼻平面时界面性变化可能涉及毛囊漏斗部（图11d）；然而在犬面部型盘状红斑狼疮中毛囊炎尚未得到专门研究。色素失禁继发于界面性反应（图11a、b），但它不是特定于这种类型的损伤，且发现于未并发鼻部皮炎的犬鼻平面上，并持续存在。基底膜区域的增厚是片状或多灶性的，但不是特异性的，因为它也发生于鼻平面的其他慢性炎性疾病，如跟地区性相关的利什曼病。浅表性真皮纤维化可能不存在或是轻度到中度的范畴。在面部型盘状红斑狼疮中继发细菌感染很常见，往往使组织学诊断复杂化。复杂化的原因是当对鼻平面活检样本的显微镜检查显示浅表性真皮“带状”炎性反应，富含淋巴细胞和浆细胞（所谓的苔藓样变浸润），而不强调界面性反应的存在时，诊断是鼻部病变为主的“犬盘状红斑狼疮”。事实上，大家认为这样的“苔藓样变”富含淋巴细胞和浆细胞的炎症是一种非特异性炎性反应，见于黏膜及附近或相关组织（口腔、鼻平面、眼睑、生殖器等）。在一项关于犬鼻部皮炎的回顾性组织学研究中，常见富含细胞的苔藓样变浸润，但只有一小部分鼻部病变的病患表现出与皮肤红斑狼疮有关的界面性皮炎。
  
In canine GDLE, in contrast to FDLE, the interface reaction is usually well developed, when an adequate number of biopsies are examined from the active margins of lesions(Fig. 12a,b). The epidermis may be atrophic or mildly hyperplastic (Fig. 12a,b) as a consequence of regional variation in severity of the interface reaction. Pigmentary incontinence can be pronounced, especially at the margins of lesions, where the interface reaction extends into zones of secondary hyperpigmentation induced by chronic inflammation (Fig. 12a-d). In chronic lesions, dermal fibrosis occasionally displaces the cell-rich inflammatory infiltrate from the superficial dermis (Fig. 12c,d). Cell-poor zones of lesion occasionally occur but often individual lymphocytes can be found in the basal layer of the epidermis in good numbers, with satellitosis of apoptotic basal keratinocytes. In GDLE, superficial epidermal apoptosis occurs, with or without lymphocytic satellitosis, which can erroneously suggest the diagnosis of erythema multiforme or morphologically related conditions. However, the collection of multiple biopsies reveals apoptosis to be most prominent in the basal epidermal layer in cases of GDLE.
在犬全身型盘状红斑狼疮中，与面部型盘状红斑狼疮相反，当从活跃的病变边缘（图12a、b）取得足够数量的活检样本时，通常会发现界面性反应。表皮可能会出现萎缩或轻度增生（图12a、b），由严重的界面性反应的区域差异引起。可能有明显的色素失禁，尤其是在病变边缘，界面性反应延伸至由慢性炎症继发的色素沉着区域（图12a-d）。在慢性病变中，真皮纤维化偶尔会促使富含细胞的炎症从真皮浅层浸润（图12c、d）。偶尔会出现细胞贫乏的病变区域，但常在表皮基底层中发现大量的单个淋巴细胞，伴随着凋亡的基底角质细胞卫星现象。在全身型盘状红斑狼疮中，会发生浅表性表皮细胞凋亡，伴随或未伴随淋巴细胞卫星现象，这可能错误地提示了多形红斑或形态相关的情况。然而，多次活检结果显示在全身型盘状红斑狼疮病例中细胞凋亡在基底表皮层中最为突出。
  
In the recent case series of canine GDLE, alopecia occurred in nearly all patients; lymphocytic interface folliculitis involved the infundibulum and extended into the isthmus. A lymphocytic mural folliculitis was also common, but it was usually milder and involved the infundibulum, isthmus and inferior hair follicle segments,typically sparing the bulbs. This mural pattern mirrors that of human DLE, where it is also called a panfollicular pattern; it is usually minimally severe, but such a pattern is insufficiently described. Sebaceous gland atrophy occurred in GDLE cases, where it was mostly mild and partial in biopsies but sometimes it was complete. It should be noted that diagnostic biopsies typically focus on epidermal changes at the margins of skin lesions where hair follicle and sebaceous gland changes might not be fully developed.
最近的一系列犬全身型盘状红斑狼疮的病例，几乎所有的病患都出现了脱毛；淋巴细胞界面性毛囊炎涉及了漏斗部并延伸到峡部。淋巴细胞毛囊壁炎也很常见，往往比较轻微并涉及了漏斗部、峡部和毛囊下部，通常保留了毛球部。这种毛囊壁性反应模式跟人类盘状红斑狼疮相似，也被称作全毛囊反应模式；它通常是最轻微的，但这样的反应没有得到充分描述。在全身型盘状红斑狼疮中可能发生皮脂腺萎缩，在活检中通常显示比较轻微和局部性，但有时是完整的。值得注意的是，诊断性活检通常集中在皮肤病变边缘的表皮变化，毛囊和皮脂腺可能不存在变化。


Immunopathology A linear deposition of IgG and IgM at the dermo-epidermal basement membrane zone (i.e. a positive LBT) of lesional skin was found in 90% of dogs with GDLE, and this proportion is similar to what is seen in human DLE lesions.Interestingly, the most commonly detected immunoreactant deposited in one series of dogs with classic FDLE was C3 (90–100%), while IgG and IgM were revealed in 40–70% of cases, respectively. In contrast, in the second case series, a positive LBT showed immunoglobulins (all classes together) and activated complement (C3) in 85–90% of 22 cases. These variable results between canine localized and generalized DLE could be related to differences in tissue fixation techniques (frozen vs. formalin), antigen retrieval methods and/or immunofluorescence staining protocols that were performed 30 years apart. To investigate the value of performing DIF in canine CLE diagnostic work-up, further studies regarding the sensitivity and specificity of a positive LBT for the diagnosis of CLE variants are warranted.
免疫病理学 lgG和lgM在皮肤表皮基底膜区域呈线性沉积（即狼疮带试验阳性），在90%患有全身型盘状红斑狼疮犬中发现了这一皮肤病变，这一比例与人类盘状红斑狼疮病变相似。有趣的是，在患有经典面部型盘状红斑狼疮的犬中检测到最多的免疫复合物沉积是C3（90%—100%），而lgG和lgM分别在40%—70%的病例中显示。相较之下，在第二个病例系列中，狼疮带试验阳性显示免疫球蛋白（所有类型一起）和活化补体（C3）在22例病例中占85%—90%。这些在犬局部和全身型盘状红斑狼疮间的各样的结果可能跟30年间进行的组织固定术（冷冻和福尔马林）、抗原修复法和/或免疫荧光染色之间的差异有关。为了探讨这些差异在犬皮肤红斑狼疮诊断中的作用，有必要进一步研究狼疮带试验阳性对皮肤红斑狼疮变异型诊断的敏感性和特异性。
Treatment and outcome Besides the obvious need for photoprotection (sun avoidance), the 2017 update of the Cochrane systematic review of interventions for human DLE reported evidence for the benefit of a potent topical glucocorticoid and the oral drugs hydroxychloroquine and acitretin (a retinoid).Furthermore, there was insufficient evidence for the efficacy of other interventions, such as topical calcineurin inhibitors (e.g. tacrolimus).
治疗和预后 除了明显的需要防光（避光）之外，2017年科克伦系统评价（CSR）更新报道了对人类盘状红斑狼疮治疗有利的强效局部糖皮质激素和口服药物羟氯喹以及维A酸（一种类维生素A）。此外，还有不充分的证据显示其他治疗措施的疗效，如局部钙调磷酸酶抑制剂（如他克莫司）。
  
Since 1992, antibiotics of the tetracycline family, with or without concurrent niacinamide (a.k.a. nicotinamide),have been suggested to be helpful for the treatment of canine immune-mediated skin diseases including FDLE. An initial report by White and colleagues showed that 14/20(70%) dogs with FDLE had a good-to-excellent response using a tetracycline-niacinamide combination; a recent retrospective study revealed a similar positive response rate in dogs with FDLE. While tetracyclineniacinamide therapy is considered to be safe, tetracycline is no longer available commercially in many countries. Although tetracycline and doxycycline were shown to be relatively similar in their effectiveness to treat the so-called canine lupoid onychodystrophy, a poorlyunderstood onychitis , therapeutic equipotency data for other canine auto-immune and immune-mediated diseases, such as DLE are unavailable; additional studies are necessary to confirm the effectiveness of substituting doxycycline or minocycline for the tetracycline used beforehand to treat dogs with CLE.
自1992年来，四环素类抗生素联合使用/不使用烟酰胺（niacinamide等同于nicotinamide）已被认为有助于治疗包括面部型盘状红斑狼疮在内的犬免疫介导性皮肤问题。White和他的同事的一份初步报告显示14/20（70%）患有面部型盘状红斑狼疮的犬对联合使用四环素-烟酰胺有良好的疗效；最近的一项回顾性研究中也在犬面部型盘状红斑狼疮得到了同样好的疗效。虽然认为四环素-烟酰胺的治疗是安全的，但在许多国家四环素已不能商用。尽管四环素和多西环素在治疗所谓的犬类狼疮甲形成异常（一种不甚了解的甲炎）时疗效相当，但对于犬其他自体免疫和免疫介导性疾病（如盘状红斑狼疮）的治疗等效性数据是不可以用的；还需要更多的研究来确认在治疗犬皮肤红斑狼疮中对于替代四环素的多西环素或米诺环素的疗效。
  
Topical tacrolimus ointment has been used successfully for the topical treatment of canine FDLE. At first,Griffies and colleagues evaluated the use of 0.1% tacrolimus ointment applied topically to the lesional (facial)skin of ten dogs with DLE, most of these dogs receiving topical tacrolimus as an adjunctive therapy to oral glucocorticoids. There was a positive response in eight dogs (80%), three of them having had an excellent improvement in skin lesions. Recently, Messinger and colleagues conducted a randomized, double-blinded, placebo-controlled crossover study to evaluate the efficacy of a lower concentration of tacrolimus ointment (0.03%) in 19 dogs with FDLE . Tacrolimus ointment, applied twice daily as monotherapy for up to 10 weeks,appeared safe and effective. A noticeable clinical improvement was seen in 13/18 (72%) of the dogs, whereas only three dogs receiving the placebo had lesions that improved. To summarize, limited outcome data suggest that topical tacrolimus ointment and/or a niacinamidecyclin combination therapy should be considered as potentially effective therapeutic options for canine FDLE.
局部他克莫司软膏已成功应用于犬面部型盘状红斑狼疮的局部治疗。一开始Griffies和他的同事评估了0.1%他克莫司软膏的使用，应用于十只患有盘状红斑狼疮的犬的皮肤病变处（面部），大多数把其作为口服糖皮质激素之外的辅助治疗。八只犬（80%）有阳性反应，其中三只犬皮肤病变得到了很好的缓解。最近，Messinger和他的同事进行了一项随机、双盲、安慰剂对照的交叉研究，以评估低浓度他克莫司软膏（0.03%）在19只患有面部型盘状红斑狼疮的犬中的疗效。单独使用他克莫司软膏，每日两次，使用10周，安全有效。在13/18（72%）的犬上有明显的临床症状缓解，而仅三只使用安慰剂的犬有病变缓解。总之，有限的结果数据显示外用他克莫司软膏和/或烟酰胺-四环素联合治疗是犬面部型盘状红斑狼疮的可能性有效治疗。
  
Skin lesions of canine GDLE appear to respond to a wide range of treatments but half of the patients experienced relapses upon the tapering of drug dosages. In a recent report , a remarkable improvement or a complete remission in GDLE skin lesions followed treatment with oral ciclosporin (mean 4.8 mg/kg once daily) along with a short course of glucocorticoids at treatment onset. Furthermore, oral hydroxychloroquine, in conjunction with topical 0.1% tacrolimus ointment application, helped induce and maintain remission of skin lesions in two dogs with GDLE .
犬全身型盘状红斑狼疮的皮肤病变似乎对很多治疗有反应，但一半的病患在药物剂量减少时出现了复发。在最近的一份报道中，在口服环孢菌素（平均剂量4.8mg/kg/，每天一次）以及治疗初期的短时间糖皮质激素的治疗，全身型盘状红斑狼疮的皮肤病变得到了明显或完全缓解。此外，在两只患有全身型盘状红斑狼疮的犬中，口服羟氯喹，联合外用0.1%他克莫司软膏，有助于诱导和维持皮肤病变的缓解。




Fig. 9 clinical characteristics of canine facial discoid lupus erythematosus.
a, b: erythematous, depigmented, ulcerated, crusted and scarred nasal lesions of FDLE in a rough collie; a discoid lesion is visible in the proximal dorsal muzzle;
(c, d): during the chronic phase of FDLE, depigmentation and scarring without inflammation are present;
(e): erosions leading to scars in a Labrador with active FDLE;
(f) depigmentation, scarring and crusting in a dog with FDLE. The presence of prominent inflammation often heralds a secondary bacterial colonization, like in the so-called MCP (courtesy of Petra Bizikova, NC State University, Raleigh)

图9犬面部型盘状红斑狼疮的临床特征
a、b：患有面部型盘状红斑狼疮的粗毛柯利牧羊犬鼻部病变：红斑、色素减退、溃疡、结痂和瘢痕；口鼻背部近端可见盘状病变；
(c、d)：在面部型盘状红斑狼疮的慢性期，存在色素减退和非炎性瘢痕；
(e)：在患有活跃性面部型盘状红斑狼疮的拉布拉多犬中糜烂导致瘢痕；
(f)：患有面部型盘状红斑狼疮的犬：色素减退、瘢痕和结痂。明显的炎性反应常提示继发的细菌感染，像所谓的黏膜脓皮病（由北卡罗莱纳州立大学罗利市Petra Bizikova提供）



Fig. 10 Clinical characteristics of canine generalized discoid lupus erythematosus.
a, b: disc-shaped, annular and polycyclic plaques with hyperpigmentation, focal depigmentation and scarring on the thorax of a Chinese crested dog with GDLE;
(c): large irregular plaque with dyspigmentation, scarring and erythema on the lateral knee of the same dog as in (a, b);
d: reticulated depigmentation with occasional plaques and focal ulceration on the abdomen;
(e):unusual “mask-like” bilateral and symmetric hyperpigmentation and dorsal proximal ulceration and scarring in another Chinese crested dog with GDLE;
(f):same dog as in (e) – classic disc-shaped dyspigmented plaque with scarring and focal ulceration and crusting;
(g): same dog as in (e) – anal and perianal dyspigmentation and scarring with focal ulceration;
(h): large polycyclic hyperpigmented and scaly plaque on the abdomen of a crossbred dog with GDLE

图10犬全身型盘状红斑狼疮的临床特点
a、b：患有全身型盘状红斑狼疮的中国冠毛犬的胸廓：盘状、环形和多环斑块，伴随着色素沉着、局部色素减退和瘢痕；
(c)：与（a、b）同一只犬，在膝外侧大面积不规则斑块，伴随着色素沉着异常/瘢痕和红斑；
d：腹部网状色素减退，伴随着偶发性的斑块和局部溃疡；
(e)：另一只患有全身型盘状红斑狼疮的中国冠毛犬，不寻常的“面具状”，两侧对称的色素沉着、背侧近端溃疡和瘢痕；
(f)：与(e)同一只犬—典型的盘状色素沉着异常的斑块，伴随着瘢痕和局部溃疡和结痂；
(g)：与(e)同一只犬—肛门和肛周色素沉着异常和瘢痕，伴随着局部溃疡；
(h)：患有全身型盘状红斑狼疮的杂交犬：腹部大面积多环色素沉着和鳞屑性斑块



Fig. 11 Histopathology of facial canine discoid lupus erythematosus.
a: in a biopsy from the nasal planum, cell-rich, lymphocytic interface dermatitis is present with a prominent band-like (lichenoid) dermal infiltrate of lymphocytes and plasma cells. Pigmentary incontinence is moderate. 100×
(b): inset box from image “a”, a short epidermal segment with well-developed interface change, where lymphocytes infiltrate predominantly the basal layer in conjunction with basal cell vacuolation, apoptosis, and loss. 400X
(c): a similar interface reaction pattern affects the epidermis of haired skin in the dorsal nasal area. 200X
(d): lymphocytic interface folliculitis and mural folliculitis of the hair follicle infundibulum. 200X

图11犬面部型盘状红斑狼疮的组织病理学
a：在鼻平面活检中，存在富含细胞、淋巴细胞界面性皮炎，伴随着明显的带状（苔藓样变）淋巴细胞和浆细胞真皮浸润。中度的色素失禁。100X
(b)：“a”中方框部分，一段短的表皮切片，良好的界面性变化，淋巴细胞主要浸润基底层，连同了基底细胞空泡化、凋亡和丢失。400X
(c)：一种相似的界面性反应影响了鼻背侧区域的被毛皮肤表层。200X
(d)：毛囊漏斗部淋巴细胞界面性毛囊炎和毛囊壁炎。200X



Fig. 12 Histopathology of generalized canine discoid lupus erythematosus
(a): in a skin biopsy from the trunk, a cell-rich lymphocytic interface dermatitis is present with prominent pigmentary incontinence. While epidermal atrophy (not shown) is classically seen in areas of prominent interface change, epidermal hyperplasia (shown here) can occur in chronic smoldering areas of lesions. 200X
(b): inset box from image “a”,lymphocytes infiltrate predominately the basal layer in conjunction with basal cell vacuolation, apoptosis, and loss. 400X
(c): some chronic lesions develop mild subepidermal fibrosis with a paucity of inflammation, while retaining pigmentary incontinence. 100X
(d): inset box from image “c”,higher magnification image shows mild subepidermal fibrosis, few inflammatory cells and prominent pigmentary incontinence. 400X
图12犬全身型盘状红斑狼疮的组织病理学
(a)：躯干处的皮肤活检，存在富含细胞的淋巴细胞界面性皮炎，伴随着明显的色素失禁。虽然表皮萎缩（未显示）在明显的界面性变化区域中很经典，表皮增生（这里已显示）也会发生在慢性进展的病变区域。200X
(b)：“a”中方框部分，主要淋巴细胞浸润基底层，连同了基底细胞空泡化、凋亡和丢失。400X
(c)：一些慢性病变发展为轻度的表皮下纤维化，非炎性反应，色素失禁。100X
(d)：“c”中方框部分，高倍镜中显示轻度的表皮下纤维化，少数炎性细胞和明显的色素失禁。400X

王帆

感谢辛蕾同学的精彩翻译~