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标题: 犬全身型盘状红斑狼疮（10例病例）的临床及显微特征-（2） [打印本页]

作者: 王帆 时间: 2021-1-27 12:33
标题: 犬全身型盘状红斑狼疮（10例病例）的临床及显微特征-（2）

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Clinical and microscopic features of generalized discoid lupus erythematosus in dogs (10 cases)

犬全身型盘状红斑狼疮（10例病例）的临床及显微特征

作者：Frane Banovic, Keith E. Linder, Maarja Uri, Michael A. Rossi and Thierry Olivry

翻译：辛蕾校对：王帆

Materials and methods

材料和方法

Case selection

病例筛选

Electronic medical records of canine CCLE cases prospectively collected at North Carolina State University’s Veterinary Hospital Dermatology Service between 2009 and 2015 were reviewed. One other case was added after an ad hoc questionnaire was sent to the VetDerm list (vetderm@lists.ncsu.edu). Dogs were included if they fulfilled all of the following three criteria:

1. a >3 month history of generalized skin lesions indicating their chronic or recurrent nature;

2. the presence of skin lesions resembling those of human GDLE; that is the presence of annular (discoid) to polycyclic plaques with dyspigmentation, adherent scaling, follicular plugging and central alopecia below the neck);

3. the presence of microscopic lesions typical of CLE (i.e. a lymphocyte-rich interface dermatitis with basal cell damage).

回顾了2009-2015年在北卡罗莱纳州立大学的兽医院皮肤专科前瞻性收集的犬CCLE的电子病历。另一个病例是在一份特别的问卷发送到VetDerm list (vetderm@lists.ncsu.edu)之后添加的。如果犬符合以下三个标准就包括在内：

1. 有>3个月的全身皮肤病变病史，提示了慢性或复发性性质；

2. 类似于人GDLE的皮肤病变；即颈部以下存在环形（盘状）到多环形斑块，伴色素沉着异常、粘附性皮屑、毛囊栓塞和中央脱毛；

3. 存在典型的CLE的显微病变（即富含淋巴细胞的界面性皮炎，伴随基底细胞损伤）。

Dogs with macular, vesiculobullous, typical and atypical target skin lesions, and histopathological findings of cytotoxic lymphocytic interface dermatitis with keratinocyte apoptosis occurring throughout multiple epidermal layers suggestive of erythema multiforme variants[minor (EMm) and major (EMM)] were excluded. We also did not include German shorthaired pointers with lesions typical of ECLE or dogs with skin lesions characteristic of MCLE.

排除那些有斑点、水疱状大疱、典型和非典型靶型皮肤病变，以及具有细胞毒性淋巴细胞界面性皮炎伴角质细胞凋亡（发生于多个表皮层，提示多形红斑亚型[轻度(EMm)和重度(EMM)]的组织病理学表现的犬。也未包括典型ECLE病变的德国短毛指示犬或皮肤病变特征为MCLE的犬。

Histopathology

组织病理学

Histopathological changes were identified and scored for severity in haematoxylin and eosin-stained skin biopsy sections. Changes were scored subjectively as absent, mild, moderate or marked and the results provided normally reflected the most developed lesional area identified in a set of biopsies. Because a cell-rich lymphocytic interface dermatitis was an inclusion criterion, histological sections were evaluated for morphological variation, distribution and severity thereof. The severity of keratinocyte apoptosis and lymphocytic satellitosis of apoptotic cells in the basal layer of the epidermis were scored separately from that in suprabasal layers. Dispersal of epidermal pigment to dermal macrophages (pigmentary incontinence), epidermal hyperpigmentation, epidermal ulcers, atrophy,hyperplasia and hyperkeratosis were also scored, and the presence of orthokeratosis and parakeratosis was noted. Basement membrane zone (BMZ) thickening, dermal fibrosis and the severity of lichenoid inflammatory infiltrates (subepidermal band-like infiltrate of inflammatory cells) were graded and the predominant inflammatory cell types were recorded. Hair follicles were evaluated for inflammatory infiltrates at all levels (folliculitis patterns), keratinocyte apoptosis, follicular atrophy,infundibular hyperkeratosis and perifollicular fibrosis. Sebaceous gland inflammation and atrophy were recorded.

对苏木精-伊红（HE）染色的皮肤活检切片进行组织病理学检查，根据其严重程度评分。主观上分为无、轻度、中度或重度，提供的结果通常反映了一组活检中确认的最成熟的病变区域。由于富含细胞的淋巴细胞界面性皮炎作为了一个纳入标准，因此使用组织学切片对形态学变化、分布和严重程度进行了评估。分别对表皮基底层和基底上层的角质细胞凋亡和凋亡细胞的淋巴细胞卫星现象的严重程度进行评分。还对表皮色素扩散至真皮巨噬细胞（色素失禁）、表皮色素沉着、表皮溃疡、萎缩、增生和角化过度进行了评分，且观察到了正角化性角化过度和角化不全性角化过度。基底膜（BMZ）增厚、真皮纤维化和苔藓样变炎性浸润（炎性细胞表皮下带状浸润）的严重程度进行分级，并记录主要炎性细胞的类型。对毛囊各层的炎性浸润（毛囊炎模式）、角质细胞凋亡、毛囊萎缩、漏斗部角化过度和毛囊周纤维化进行等级评估。记录皮脂腺炎性反应和萎缩。

Direct immunofluorescence (IF)

直接免疫荧光（IF）

In order to detect the presence of immunoglobulin (IgG, IgA, IgM)and activated complement C3 deposits along the BMZ, direct IF was performed as described previously. The frequency, distribution (including extension along the basement membrane of hair follicles)and characteristics of deposits were described subjectively. The detection of a thin-to-thick linear deposit at the BMZ, either continuous or interrupted (i.e. patchy), was considered a positive “lupus band test”(LBT).

为了检测沿BMZ存在的免疫球蛋白（IgG、IgA、IgM）和活化补体C3沉积，按之前所述直接IF。主观上描述沉积的频率、分布（包括延伸至毛囊基底膜）和特征。在BMZ检测到连续或间断的（即片状）一层由薄到厚的线性沉积，则“狼疮带试验”（LBT）为阳性。

Evaluation for systemic lupus erythematosus

系统性红斑狼疮的评估

In order to rule out concurrent systemic lupus erythematosus (SLE),further investigations included combinations of serum antinuclear antibodies (ANA) titre, serum chemistry profile, complete blood count and urinalysis. The detection of serum ANA was performed using a variety of techniques depending upon the laboratory used for such testing.

为了排除并发的系统性红斑狼疮（SLE），进行了进一步检查：血清抗核抗体（ANA）滴度、血清生化分析、全血细胞计数和尿检。血清ANA的检测使用的各种技术根据检测的实验室而定。

Clinical management and prognosis

临床治疗及预后

Data on signalment, history, clinical signs and treatment outcome for each case were collected and analysed. Details on previous, initial and maintenance immunosuppressive therapy (dose, frequency and length of treatment for each drug or combination of drugs) were reviewed for each case. Additionally, any adverse effects related to drug therapy, concurrent diseases and frequencies of initial disease relapses were reported.

收集和分析每个病例的特征、病史、临床症状和治疗效果。对每个病例详细回顾了先前的、初始和维持的免疫抑制治疗（每种药物或药物组合的剂量、频率和治疗时间）。此外，还报告了与药物治疗、并发疾病和初始疾病复发频率有关的任何不良反应。

Results

结果

Clinical summary

临床总结

Ten dogs met the inclusion criteria. Three of the cases included herein have been previously published as single case reports.

有10只犬符合纳入标准。本文包含的病例中有3例以前曾作为单一病例报告发表。

Selected dogs included seven pure bred and two cross bred dogs: two were Chinese crested dogs and 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 five and 12 years of age (median 9 years),whereas the female-to-male ratio was one; all dogs were castrated. Three dogs had a previous history of a skin disease: one dog each suffered from either cutaneous melanocytoma, atopic dermatitis or liver associated necrolytic migratory erythema (NME).

选定的犬包括7只纯种犬和2只杂交犬：2只中国冠毛犬和拉布拉多猎犬；以下纯种犬各1只：迷你杜宾犬、兰波格犬、西施犬和玩具贵宾犬。GDLE的皮肤病变的发病年龄在5-12岁不等（中位年龄为9岁），且雌雄比例相当；所有犬均绝育。3只犬有过皮肤病病史：患犬各有皮肤黑色素细胞瘤、特应性皮炎或肝脏相关的坏死松懈性游走性红斑（NME）。

Before the initial visit, skin lesions had been present between 3 and 24 months (median: 9 months). The initial lesions most commonly reported by the owners were erythematous macules, papules and plaques with erosions and scaling; these were first noticed usually on the neck and trunk. Upon presentation all dogs had lesions on the neck, dorsum and lateral thorax. Lesions were also present on the head in seven of 10 cases (70%), whereas abdomen and medial and lateral aspects of proximal limbs were affected in eight dogs (80%). According to the inclusion criteria, skin lesions included generalized multifocal, annular (discoid) to polycyclic plaques with dyspigmentation, an erythematous margin, adherent scaling, follicular plugging and central alopecia (Figure 1). In nine dogs(90%), the plaques evolved with mild to moderate ulcerations, central atrophic or hypertrophic scarring and pigmentation changes (depigmentation and hyperpigmentation; Figure 1). Generalized hyperpigmented to depigmented macules/patches with occasional thick adherent scaling, central alopecia and erythematous margin were seen in nine dogs (90%; Figure 2). In one apricot miniature poodle, reddish brown patches and plaques with large scales were present throughout the body, and there was extensive spontaneous alopecia that occurred even outside of the more focal inflammatory lesions (Figure 3).

在首诊之前，皮肤病变出现时间在3个月-24个月之间（中间值：9个月）。宠主报告的最常见的最初病变有红斑性斑点、丘疹和斑块，伴随着糜烂和皮屑；首次发现通常是在颈部和躯干。就诊时所有犬在颈部、背部和胸侧都有病变。在10例病例中，有7例（70%）头部也有病变，有8例（80%）的腹部和近端肢体的内外侧亦会发病。根据纳入标准，皮肤病变包括全身多灶性、环状（盘状）至多环斑块，伴随着色素沉着异常、边缘红斑、粘附性皮屑、毛囊栓塞和中央脱毛（图1）。在9只犬（90%）中，斑块发展为轻度至中度溃疡、中央萎缩或增生性瘢痕和色素改变（色素减退和色素沉着；图1）。在9只犬（90%；图2）中可见全身色素沉着到色素减退的斑点/斑片，偶然会有较厚的粘附性皮屑、中央脱毛和边缘红斑。一只杏黄色的迷你贵宾犬，全身出现大块皮屑的红棕色斑片和斑块，甚至在局灶性的炎性病变之外也出现了广泛性的自发性脱毛（图3）。

Four dogs (40%) had mucocutaneous regions involved with plaques appearing most commonly on or around the genitalia (Figure 4). One Chinese crested dog concurrently had depigmentation, deep erosions and loss of architecture of the nasal planum (Figure 4). Hyperpigmented macules/plaques with adherent scaling and follicular plugging were observed on the concave pinnae and caudal (lateral) ear margins of three dogs (Figure 5a,b).An unusual pattern of reticulated (net-like) hyperpigmentation was visible on the ventral abdomen and lateral thorax in two cases (Figure 5c,d).

有4只犬（40%）皮肤黏膜部位出现斑块，常发生在生殖器或生殖器周围（图4）。1只中国冠毛犬同时发生色素减退、深度糜烂和鼻平面结构缺失（图4）。在3只犬的耳廓凹面和耳缘尾侧（侧面）出现色素沉着的斑点/斑块，伴随着粘附性皮屑和毛囊栓塞。2例病例在腹侧和胸侧出现不常见的网格状（网状）色素沉着模式。

There were no systemic signs observed in any dog, apart from the pruritus and pain at the site of lesions in four (40%) and three dogs (30%), respectively. A complete blood count revealed mild regenerative anaemia, serum chemistry results included mild hypoalbuminemia and moderate elevations of liver enzymes in two of 10 dogs (20%), whereas urinalysis results were unremarkable in all dogs.

除了有4只犬（40%）病变处瘙痒、3只犬（30%）病变处疼痛外，未观察到其他犬有全身性症状。全血细胞计数显示轻度再生性贫血，血清生化轻度低蛋白血症和肝酶中度升高，而在所有犬中尿检结果未见明显异常。

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Figure 1. Typical skin lesions of generalized discoid lupus erythematosus (GDLE) in dogs at initial presentation

(a) Two annular hyperpigmented plaques with focal central depigmentation and scarring (Case 2).

(b) An annular to polycyclic plaque consisting of central alopecia, erythema, depigmentation and atrophic scarring with peripheral hyperpigmented rim and scaling (Case 3).

(c, d) Annular “coin-shaped” plaques with characteristic depigmentation, atrophic (c) and hypertrophic (d) scarring at inactive centre and hyperpigmentation with erosions and adherent scaling at peripheral active border (Case 5).

图1 犬全身型盘状红斑狼疮（GDLE）首诊时的经典皮肤病变。

（a）2个环状色素沉着的斑块，伴随着局灶性中央色素减退和瘢痕（病例2）。

（b）1个环状至多环的斑块，由中央脱毛、红斑、色素减退和萎缩性瘢痕组成，伴随着周边的色素沉着和皮屑（病例3）。

（c、d）环状“硬币形”的斑块，存在典型特征性的色素减退、非活跃中心的萎缩性（c）和肥厚性（d）的瘢痕及色素沉着，伴有糜烂和周边活跃区粘附性皮屑（病例5）。

Histopathology

组织病理学

A total of 25 biopsy specimens were evaluated (2-4 per dog). The cell rich lymphocytic interface dermatitis was present in all cases (this was an inclusion criterion,however). Moderate to marked basal cell degeneration, also an inclusion criterion, consisted of keratinocyte vacuolation, apoptosis and/or disappearance (Figure 6). The distribution of these lesions varied from diffuse to focal or peri-ulcerative; in two cases the severity of basal cell injury led to microscopic intrabasal cleft formation. Apoptosis in suprabasal epidermal layers (Figure 7) was frequently observed (eight of 10; 80%): it was mild (1-10 cells per biopsy section) in five cases (50%) and moderate (10-25 cells per section) in three others (30%). Overall, the suprabasal apoptosis was less severe than the interface change observed for each case. Lymphocytic satellitosis of apoptotic basal cells (Figure 6) was robust and present in all cases, whereas the lymphocyte targeting of apoptotic cells occurred in fewer dogs(four of eight; 50%). Similarly, lymphocytic exocytosis was prominent in the deep epidermis and was absent or mild in superficial epidermal layers. Foci of epidermal atrophy were uncommon (three of 10; 30%), and most cases(seven of 10; 70%) exhibited mild to moderate, diffuse, epidermal hyperplasia. Interface dermatitis was associated with foci of partial epidermal collapse, with flattening and elongation of keratinocytes occurring in an otherwise hyperplastic epidermis (Figure 6). A mild and occasionally marked orthokeratotic hyperkeratosis occurred in most cases with occasional interruption by foci of parakeratosis. Moderate to marked pigmentary incontinence colocalized with foci of epidermal depigmentation and/or areas of epidermal hyperpigmentation in all cases. Moderate to marked BMZ thickening was detected in focal areas in several cases (six of 10; 60%).

一共评估25个活检样本（每只犬2-4个）。所有病例都存在富含淋巴细胞的界面性皮炎（然而此为一个纳入标准）。中度至重度的基底细胞变性也是一个纳入标准，包括了角质细胞空泡化、细胞凋亡和/或缺失（图6）。这些病变的分布从弥散性到局灶性或周围溃疡不等；在2例病例里基底细胞损伤的严重程度导致显微镜下形成基底开裂。常见基底上表皮层凋亡（图7）（10例中占8例；80%）：5例（50%）为轻度（每个活检切片1-10个细胞）和3例（30%）为中度（每个活检切片10-25个细胞）。总的来说，基底上层细胞凋亡程度低于每个病例观察到的界面变化。基底细胞凋亡的淋巴细胞卫星现象（图6）在所有病例中都明显存在，而在少数犬中淋巴细胞靶向攻击导致细胞凋亡（8只中有4只；50%）。同样，淋巴细胞外排作用在表皮深层中较多出现，但在表皮浅层中较少出现或不出现。表皮萎缩的病灶不常见（10只中有3只；30%），多数病例（10只中有7只；70%）表现为轻度到中度、弥散性的表皮增生。界面性皮炎与局部表皮塌陷病灶有关，其他增生的表皮中角质细胞会变平和延长（图6）。多数病例中会出现轻度和偶然重度的正角化性角化过度，偶尔会因角化不全病灶而中断。在所有的病例中，中度至重度色素失禁与表皮色素减退病灶和/或表皮色素沉着区共存。在一些病例（10例中占6例；60%）的局灶性区域发现中度至重度的BMZ增厚。

A focal to diffuse and mild to marked lichenoid, dermal inflammatory infiltrate composed of lymphocytes mixed with a similar amount or fewer plasma cells was seen in eight cases (80%; Figure 6). In two dogs that lacked the lichenoid infiltrate, as well as in cases where lichenoid infiltrates showed limited distribution in comparison to the interface dermatitis, the lymphocytes were still numerous in the basal epidermal layer. A mild perivascular inflammatory pattern was observed in the superficial dermis, whereas the middle and deep dermis usually contained minimal or no inflammation (Figure 6). A mild to marked superficial, laminar dermal fibrosis (five of 10; 50%) extended from the BMZ, and was sometimes paucicellular. Occasional ulcers (four of 10; 40%) were associated with mild neutrophilic dermatitis and crusts. Lesions indicative of vasculitis or panniculitis were not observed in any section.

在8例病例（80%；图6）中可见局灶性到弥散性和轻度到重度的苔藓样变、真皮层由淋巴细胞和同等数量或更少数量的浆细胞组成的炎性细胞浸润。在未发现苔藓样变浸润的2只犬中，与有苔藓样变的病例一样，比较有限分布的界面性皮炎的表现，表皮基底层仍存在许多淋巴细胞。真皮浅层观察到轻度的血管周炎症模式，而在真皮的中部和深部通常是轻度或没有炎症反应（图6）。从BMZ延伸到真皮层的轻度到重度的浅表片状纤维化（10只中有5只；50%），且有时是乏细胞性的。偶见溃疡（10只中有4只；40%），伴有与轻度中性粒细胞性皮炎和结痂。在任何切片中都未观察到血管炎或脂膜炎的病变提示。

Histological changes in adnexa were evaluated for eight of 10 dogs (80%), excluding the two hairless Chinese crested dogs. Mild to moderate perifollicular lymphoplasmacytic inflammation was observed in all eight cases; the inflammation surrounded the infundibulum and tapered inwards through the level of the isthmus (Figure 8). A moderate to marked lymphocytic interface folliculitis involved the hair follicle infundibula of these eight cases, and the changes were similar to the basal cell degeneration, suprabasal apoptosis and lymphocytic exocytosis with satellitosis observed in the epidermis (Figure 8). The interface folliculitis that extended to the isthmus was usually mild and occasionally moderate; however, this distinction was difficult to make in cases of advanced follicular atrophy. Lymphocytic mural folliculitis (Figure 8) was mild to moderate in the infundibulum of seven cases(88%) and usually milder in the lower follicular segments of all cases. Scattered individual and loose clusters of lymphocytes infiltrated the external root sheath of anagen stage, telogen stage and atrophic follicles. Very rarely, occasional individual lymphocytes infiltrated an anagen hair bulb. Hair follicle atrophy was observed in all cases and (Figure 8) ranged from diffuse and advanced to focal and mild, with atrophic follicles sometimes bordering anagen follicles. Sebaceous gland atrophy was also seen in all dogs and was more commonly associated with atrophic hair follicles; the severity ranged from mild and partial in at least one biopsy. The inflammation within the glands was limited to the walls of sebaceous ducts that sometimes contained a few lymphocytes; infiltration of sebaceous gland lobules was not observed. Follicular hyperkeratosis and infundibular dilation were mild or absent in most cases. Perifollicular fibrosis was uncommon (one of eight cases; 13%), mild and restricted to the infundibulum.

对10只中的8只犬（80%）附件的组织学变化进行了评估，不包括2只无毛的中国冠毛犬。在全部8例病例中均观察到轻度到中度的毛囊周淋巴浆细胞性炎症；炎症位于漏斗部周围，并沿峡部平面向内逐渐减轻（图8）。在这8例病例中，位于毛囊漏斗部有中度至重度淋巴细胞界面性毛囊炎，且其变化类似于表皮的基底细胞变性、基底上层细胞凋亡和淋巴细胞外排伴卫星现象（图8）。延伸到峡部的界面性毛囊炎通常是轻度，偶见中度；然而在晚期毛囊萎缩的病例中这种区分还是很困难的。7例病例（88%）中毛囊漏斗部有轻度至中度的淋巴细胞毛囊壁炎（图8），所有病例的毛囊下部病变通常都较轻。在生长期、终止期和毛囊萎缩期的外根鞘内均有个别散在的和松散成簇的淋巴细胞浸润。生长期的毛球部偶见个别淋巴细胞浸润的情况极罕见。所有病例中都可观察到毛囊萎缩，范围从弥散性、晚期到局灶性、轻度，有时萎缩的毛囊与紧邻生长期毛囊。所有犬也可见皮脂腺萎缩，更常见的是与萎缩的毛囊相关；至少有一处活检显示严重程度为从轻度到局部。腺体内的炎症仅限于皮脂腺腺管壁，有时含有少量淋巴细胞；未观察到皮脂腺小叶浸润。多数病例出现较轻或没有毛囊角化过度和毛囊漏斗部扩张。毛囊周纤维化并不常见（8例中占1例；13%），轻度且仅限于毛囊漏斗部。

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Figure 2. Close up of the macular/patch type skin lesions present on the thorax of dogs with GDLE

(a) Well demarcated annular to polycyclic hyperpigmented patches with severe adherent scaling, partial alopecia and mild scarring in the centre (Case 10).

(b) Well demarcated annular hyperpigmented macules to patches with prominent follicular plugging, scaling, peripheral erythematous rim and central ulceration (Case 3).

(c, d)Hyperpigmented annular macules and patches with central loss of tissue architecture and prominent silver adherent scales surrounded by a mild peripheral erythematous margin (d) (Case 7).

图2 近距离观察犬GDLE胸部的斑点/斑片类型的皮肤病变。

（a）边界清晰的环状至多环状色素沉着斑片，伴随着严重的粘附性皮屑、局部脱毛和中央轻度瘢痕（病例10）。

（b）边界清晰的环状色素沉着的斑点至斑片，伴随着明显的毛囊堵塞、皮屑、周围边缘红斑和中央溃疡（病例3）。

（c、d）色素沉着的环状斑点和斑片，伴随着中央组织结构缺失和明显的银色粘附性皮屑，围绕轻度的周围边缘红斑（d）（病例7）。

[attach]61674[/attach]

Figure 3. Skin lesions of generalized discoid lupus erythematosus in an apricot poodle. Generalized brown coloured patches and plaques with large scales and extensive spontaneous alopecia throughout the body (a, b, d) and involving the dorsum of head and ears (c) (Case 9).

图3 一只GDLE杏黄色贵宾的皮肤病变。全身棕色斑片和斑块，伴随着大块皮屑和广泛性的自发性脱毛（a、b、d），并涉及了头顶和耳部（c）（病例9）。

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Figure 4. Skin lesions affecting mucocutaneous junctions in dogs with GDLE

(a) Well-demarcated bilaterally symmetrical diffuse hyperpigmentation with adherent scaling and partial alopecia on the muzzle, including periocular areas. Central depigmentation, scarring and ulcerations involve the nasal planum and bilaterally the medial canthus of the eyes (Case 5).

(b) Multifocal hyperpigmented macules with mild erythematous rim on prepuce (Case 5).

(c) Anal/perianal diffuse hyperpigmentation with multifocal depigmentation, scarring and adherent scaling. Note the linear ulcerations in friction areas; this case suffered from liver associated necrolytic migratory erythema. The development of GDLE type skin lesions in this area is suggestive of the Koebner phenomenon (Case 5).

(d) Diffuse hyperpigmented alopecic patch/plaque with multifocal depigmentation, scarring and ulceration at the external vulva and perivulvar skin (case 7x).

图4 犬GDLE皮肤黏膜交界处的皮肤病变。

（a）边界清晰、双侧对称的弥散性色素沉着，伴随着粘附性皮屑和局部脱毛，包括了眼周区域。中央色素减退、瘢痕和溃疡，涉及了鼻平面和双眼内眦（病例5）。

（b）多灶性色素沉着的斑点，伴随着包皮上轻度边缘红斑（病例5）。

（c）肛门/肛周弥散性色素沉着，伴随着多灶性色素减退、瘢痕和粘附性皮屑。注意摩擦区域的线性溃疡；此病例为肝脏相关的坏死松懈性游走性红斑。该区域GDLE皮肤病变的发展提示了Koebner现象（病例5）。（Koebner现象：Koebner反应/同构反应，现泛指患有某种皮肤病的患者外观正常的皮肤在非特异性损伤后出现愿皮肤病类似皮损的现象）

（d）外阴部和外阴周皮肤弥散性色素沉着脱毛斑片/斑块，伴随着多灶性色素减退、瘢痕和溃疡（病例7x）。

Immunopathology

免疫病理学

Antinuclear antibody serology was determined for eight of 10 dogs (80%) and low ANA serum titres (1:20-1:40) were detected in seven of these eight cases (88%). Although ANA serology was positive at low dilutions in most dogs, the lack of systemic signs and laboratory results to suggest renal or haematological involvement excluded a diagnosis of coexisting SLE. Direct IF revealed fine to thick, patchy deposition of IgG and IgM along the dermo-epidermal junction of lesional paraffin-embedded skin sections in nine of 10 dogs (90%) (Figure 9). An additional positive LBT for IgA and C3 was found in three (30%) and two (20%) cases, respectively. Positive LBTs were detected for four and two immunoreagents in three (30%) and seven (70%) of 10 dogs, respectively.

对10只犬的8只（80%）进行了抗核抗体血清学检测，这8例中有7例（88%）检测的ANA血清滴度较低（1:20-1:40）。虽然多数犬在低稀释时ANA血清学呈阳性，但缺乏全身症状和实验室结果表明了肾脏或血液学的参与，排除了并发的SLE。10只犬中有9只（90%）的石蜡包埋皮肤病变切片，直接IF显示沿真皮-表皮交界处lgG和lgM由薄到厚呈片状沉积（图9）。另外3例（30%）显示lgA的LBT阳性，2例（20%）C3的LBT阳性。10只犬中3只（30%）检测到4种免疫试剂LBT阳性，7只（70%）检测到2种免疫试剂LBT阳性。

Clinical management and prognosis

临床治疗及预后

Information on treatment outcome was available for all dogs. Prior to the initial visit, the skin lesions were present between three and 24 months, with a median of approximately 9 months. Drugs prescribed prior to the diagnosis of GDLE was made included short courses of antimicrobial drugs (e.g. cefalexin, clindamycin, enrofloxacin; eight of 10 cases, 80%) and a single glucocorticoid course (four of 10 cases, 40%); these regimens resulted in only transient improvement of skin lesions in two dogs(20%). A spontaneous resolution of cutaneous lesions was not seen in any case. In one dog, an initial four month combination of doxycycline and niacinamide,thrice daily at appropriate dosages (250-500 mg per dog three times daily), did not result in clinical improvement.

获得了所有犬的治疗信息。在初次回访前，皮肤病变出现在3-24月龄，中位年龄约为9月龄。在诊断为GDLE前处方药物包括短期抗菌药物（如头孢氨苄、克林霉素、恩诺沙星；10例占8例，80%）和单次糖皮质激素疗程（10例占4例，40%）；这些治疗方式仅改善了2只犬（20%）的皮肤病变。所有病例中都没有发现皮肤病变能自愈。在1只犬中，最初的4个月联合使用多西环素和烟酰胺，适当剂量每天3次（每只犬按250-500mg每天3次），临床症状未改善。

Once the co existing SLE was ruled out and the diagnosis of GDLE diagnosis had been made, a recommendation to avoid excessive sun exposure was given to the owners for all dogs, and three different therapeutic modalities were initiated: Group 1 (six of 10 dogs; 60%) was commenced with oral glucocorticoids (1-2 mg/kg/day, progressively tapered over a month) given with oral ciclosporin (range 3.3-6 mg/kg, mean 4.8 mg/kg once daily, Atopica; Elanco Animal Health; Greenfield, IN,USA), in conjunction with ketoconazole in three dogs (range 1-3.3 mg/kg, mean 2.3 mg/kg once daily; Teva Pharmaceuticals; Sellersville, PA, USA), Group 2 (three of 10 dogs; 30%) received topical tacrolimus 0.1% ointment(twice daily, Protopic; Astellas Pharma; Deerfield, IL, USA) and oral hydroxychloroquine (HCQ) (5 mg/kg once daily, Gallipot; St Paul, MN, USA); and a single dog (10%) was started solely on the tetracycline/niacinamide combination (45 mg/kg of each drug three times a day). A complete remission of clinical signs (scarring alopecia remained in some lesions) following treatment occurred after 3-6 months (median 4.5 months) in five dogs (50%; two dogs each from Group 1 and 2; the dog from Group 3), whereas an approximately 75% partial remission was seen after 1-6 months (median 5.5 months) in the other five dogs (50%). An attempt to discontinue or taper the treatment resulted in the rapid recurrence of typical skin lesions in six dogs (60%); re-introducing the treatment modality at lower frequency of administration (e.g. ciclosporin every other day; topical tacrolimus twice weekly without HCQ) maintained remission of clinical signs in five dogs. In one dog that had several disease flares while receiving HCQ, oral ciclosporin (5 mg/kg once daily) was introduced and induced complete clinical remission over the following four months.

一旦排除了并发的SLE并确诊了GDLE后，建议主人为所有犬进行防晒，并提出了三种不同的治疗方案：第1组（10只犬中有6只；60%）开始口服糖皮质激素（1-2mg/kg/d，1个月后逐渐减量），口服环孢素（阿托皮卡，3.3-6mg/kg，平均4.8mg/kg，每天1次；Elanco公司；美国印第安纳州格林菲尔德），连用酮康唑（1-3.3mg/kg，平均2.3mg/kg，每天1次；梯瓦制药；美国宾夕法尼亚州塞勒斯维尔）。第2组（10只犬只中有3只；30%）外用0.1%他克莫司软膏（普特彼，每天2次；安斯泰来制药；美国伊利诺伊州迪尔菲尔德）和口服羟氯喹（HCQ）（5mg/kg，每天1次，Gallipot公司；美国明尼苏达州圣保罗）；1只犬（10%）开始仅连用四环素/烟酰胺（每种药物45mg/kg，每天3次）。治疗3-6个月后（中位时间4.5个月），5只犬（50%；2只犬来自第1组；2只犬来自第2组；1只犬来自第3组）临床症状完全缓解（一些病变中仍存在瘢痕性脱毛），而其他5只犬（50%）在1-6个月后（中位时间5.5个月）约75%的部分缓解。试图停止或减少治疗导致6只犬（60%）典型的皮肤病变迅速复发；在5只犬中以较低的给药频率调整治疗方式（如：隔天1次环孢素；每周2次外用他克莫司而未使用HCQ），临床症状得到缓解。有1只犬在接受HCQ治疗时突发几种疾病，开始口服环孢素（5mg/kg，每天1次）4个月使临床症状完全缓解。

[attach]61676[/attach]

Figure 5. Canine GDLE

(a) Hyperpigmented macules and plaques with erythema, adherent scaling, crusting and follicular plugging of the concave pinnae and caudal (lateral) pinna margin. Note that this this pattern of clinical involvement is highly specific for human discoid lupus erythematosus.(Case 3).

(b) Diffuse hyperpigmentation with adherent scaling on the pinna (Case 5).

(c) An unusual pattern of reticulated (net-like) hyperpigmentation with alopecia on the ventral abdomen. Inset: Higher magnification shows classic“coin-shaped” plaques with central depigmentation, scarring and peripheral hyperpigmentation (Case 3).

(d) Reticulated hyperpigmentation pattern developing from coalescing GDLE skin lesions (Case 2).

图5 犬GDLE

（a）耳廓凹面和耳缘尾侧（外侧）色素沉着的斑点和斑块，伴随着红斑、粘附性皮屑、结痂和毛囊堵塞。值得注意的是，这种临床表现模式对人DLE有高度特异性（病例3）。

（b）耳廓上弥散性色素沉着，伴随着粘附性皮屑（病例5）。

（c）腹侧一种不常见的网状色素沉着模式，伴随着脱毛。方框处：高倍镜下经典的“硬币形状”斑块，伴随着中央色素减退、瘢痕和外周色素沉着（病例3）。

（d）网状色素沉着由合并的GDLE皮肤病变发展而来（病例2）。

作者: bateer578 时间: 2021-1-27 21:57
感谢分享，如此高级的知识

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学习了。

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