犬全身型盘状红斑狼疮（10例病例）的临床及显微特征-（1）

王帆

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

Background–Generalized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic cutaneous lupus erythematosus (CLE) that is not well characterized.

Hypothesis/Objectives–We report herein the signalment, clinical signs, treatment outcome, histopathology and immunological findings of 10 dogs with GDLE.

Methods–Inclusion criteria were: (i) a >3 month history of generalized skin lesions indicating a chronic or recurrent nature; (ii) skin lesions resembling those of human GDLE; (iii) histopathology of CLE (lymphocyte-rich interface dermatitis). Direct immunofluorescence (IF) and antinuclear antibody serology were investigated whenever possible.

Results–Various breeds were affected in their mid- to late adulthood. Selection criteria of generalized multifocal, annular(“discoid”)to polycyclic plaques with pigment changes, erythematous margin, adherent scaling,follicular plugging and central alopecia were shown in all dogs. In nine dogs, plaques contained mild to moderate central scarring with and/or hyperpigmentation. There were no dogs in which the disease progressed to systemic lupus erythematosus within a median follow-up of 2.5 years. Per inclusion criteria, interface dermatitis occurred with basement membrane zone (BMZ) thickening, suprabasal apoptosis and/or dermal fibrosis in some dogs. Infundibular interface folliculitis was common; it sometimes transitioned to mural folliculitis in lower follicle segments, and occurred with follicular and sebaceous gland atrophy. The direct IF revealed of immunoglobulin IgG and IgM at the BMZ. Lesions responded to a variety of treatments, including ciclosporin, hydroxychloroquine, topical tacrolimus and tetracycline/niacinamide. Relapses were common after medications were tapered.

Conclusions and clinical importance–These observations support the existence of a canine homologue of human GDLE.

摘要

背景—全身型盘状红斑狼疮（GDLE）是最近发现的一种犬慢性皮肤型红斑狼疮（CLE）的变异型，并不清楚其特征。

假设/目的—本文报道了10只犬GDLE的疾病特征、临床症状、治疗效果、组织病理学和免疫学发现。

方法—纳入标准是：(i)有超过3个月的全身皮肤病变史，提示了慢性或复发性特征；(ii) 皮肤病变类似于人GDLE；(iii)CLE的组织病理学（富含淋巴细胞的界面性皮炎）。可能情况下，可采用直接免疫荧光（IF）和抗核抗体血清学。

结果—不同的品种会在成年中期到晚期发病。所有犬均表现全身多灶性、环状（“盘状”）到多环斑块，伴有色素改变、边缘红斑、粘附性皮屑、毛囊栓塞和中央脱毛。在9只犬中，斑块中央轻度到中度瘢痕，和/或伴有色素沉着。在中位时间为2.5年的回访中，没有犬发展为系统性红斑狼疮（SLE）。根据纳入标准，每只患犬都有界面性皮炎，伴随着基底膜（BMZ）增厚、基底上层细胞凋亡和/或有些犬有真皮纤维化。常见漏斗部界面性毛囊炎；有时会在毛囊下部转化为毛囊壁炎，伴随毛囊和皮脂腺萎缩。直接IF显示在BMZ有免疫球蛋白lgG和lgM。病变对多种治疗有效，包括环孢素、羟氯喹、外用他克莫司和四环素/烟酰胺。常药物减量后常见复发。

结论与临床意义—这些观测支持了犬与人的GDLE为同源物的结论。

Introduction

介绍

In humans, the Sontheimer–Gilliam classification divides the skin lesions that can be encountered in lupus erythematosus (LE) into those with characteristic microscopic changes of lymphocyte-rich interface dermatitis with basal keratinocyte damage (i.e.“lupus-specific”skin diseases = cutaneous LE or CLE) and those without such microscopic pattern (i.e.“LE-nonspecific”skin diseases). Furthermore, LE-specific skin diseases are subdivided into acute, subacute and chronic types (i.e. ACLE,SCLE and CCLE, respectively); these designations refer to both the lesional morphology and the average duration of individual skin lesions.A purely histological classification is impossible, because a significant overlap exists between the various clinical subtypes of CLE.

人医中，根据Sontheimer–Gilliam分类法，把红斑狼疮（LE）皮肤病变分为显微镜下可见富含淋巴细胞的界面性皮炎伴随着基底角质细胞损伤（即“特异性狼疮”皮肤病=皮肤型LE或CLE）和那些没有此种显微特征的（即“非特异性LE”皮肤病）。此外，特异性LE皮肤病可细分为急性、亚急性和慢性（即分别是ACLE、SCLE和CCLE）；这些名称涉及了病变的形态和单个皮肤病变的平均存在时间。单纯靠组织学分类是不可能的，因为CLE的各种临床亚型间存在明显的重叠。

Among the several variants of human CCLE [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 the generalized form, in which skin lesions also occur below the neck. The classic skin lesions of human DLE usually consist of early erythematous and variably scaly macules or papules that slowly evolve into 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 generalized DLE have been reported in patients of differing ethnic groups, such as Indian people from the Asian subcontinent. In these patients, the morphological appearance of lesions can vary from hyperpigmented macules to hyperkeratotic, hyperpigmented plaques with erythematous border.

人CCLE的几个亚型中[如盘状LE（DLE）、疣状（角化过度）LE、冻疮型LE、肿胀性狼疮和深部狼疮]，DLE最常见：它分为多种局灶型，皮肤病变限于头部和颈部和全身型，皮肤病变也出现在颈部以下。人DLE的经典皮肤病变通常包括早期红斑和各样的皮屑性斑点或丘疹，慢慢演变为一个硬币形状（即盘状）、粘附性皮屑的斑块、毛囊栓塞（即粉刺）和可能继发于炎症反应的周围色素沉着。这些盘状斑块合并后可发展为中央瘢痕和色素减退。已有报道在不同种族中病患全身型DLE的非典型表现，如来自亚洲次大陆的印第安人。这些病患的病变形态外观从色素沉着的斑点到角化过度、伴有边缘红斑的色素沉着的斑块。

At this time, well characterized manifestations of canine CLE that fall under the category of CCLE include the long recognized, localized, facial-predominant DLE,exfoliative CLE (ECLE) of German shorthaired pointers and mucocutaneous lupus erythematosus (MCLE).Several single case reports have suggested the existence of other generalized variants of CCLE in dogs.

目前，归类于CCLE的犬CLE的特征性表现包括一直公认的局灶性、主要面部发病的DLE，德国短毛指示犬的表皮剥脱型皮肤红斑狼疮（ECLE）和皮肤黏膜红斑狼疮（MCLE）。有几份个案报告犬中存在其他全身型CCLE的变异型。

   

The purpose of this paper is to describe the clinical features, histopathology, immunopathology and treatment outcome of 10 dogs with skin lesions resembling those of generalized DLE (GDLE) of humans. Herein, we propose canine GDLE to be a second variant to be added to the classic facial (i.e. localized) DLE first reported in dogs in 1979.

本文的目的是描述了10只皮肤病变类似于人GDLE的犬的临床特征、组织病理学、免疫病理学和治疗效果。这里我们建议将犬GDLE作为第二亚型加入到1979年首次报道的经典面部（即局部型）DLE中。

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