大疱性类天疱疮临床评估指标的研究进展

大疱性类天疱疮是一类自身免疫性疱病。针对自身免疫性大疱病,有专门的评分指标用以评估病情的严重程度和对治疗的反应。常用的评价指标有自身免疫性疱病严重程度评分,专门针对大疱性类天疱疮的大疱性类天疱疮疾病面积指数评分,以及其他的一些评分方式。自身免疫性大疱病严重程度评分已经经过了效度检验,广泛地应用在寻常型天疱疮和其他一些自身免疫性疱病的评估中。大疱性类天疱疮疾病面积指数评分尚处于检验的过程中,应用该评分的临床试验较少。上述两种评分方式均对全身的皮肤、黏膜皮损情况,主观瘙痒程度进行了评分。     

大疱及疱疹性皮肤病

20140817自身免疫性疱病严重程度评分系统/刘振锋（四军大西京医院）,王刚∥中华皮肤科杂志.-2013,46（4）.-295-297 自身免疫性疱病（AIBD）是一组少见的表现为皮肤红斑、水疱、大疱的皮肤病,不同程度地影响患者的生活质量。缺乏稳定、合理的评分系统使得治疗方案的对照研究不能有效进行,影响临床医生选择最佳的治疗方案。量化疾病严重程度不但能够判断病情预后,而且可以使同一患者不同治疗阶段以及不同患者之间进行对照研究,从而有效地评估治疗方案。     

自身免疫性疱病的表位扩展现象

表位扩展常发生在自身免疫性疱病患者中, 该类患者由于表位扩展使得更多的抗原表位暴露, 引起原疾病加重、转化或并发其他疾病。随着表位扩展的免疫学证据日益增加, 越来越多的学者认识到表位扩展在疾病发展的过程中发挥重要作用。本文从不同类型类天疱疮、不同类型天疱疮、天疱疮与类天疱疮、自身免疫性疱病与其他皮肤病的并发或转化四个方面, 介绍自身免疫性疱病中的表位扩展现象。     

线状IgA大疱性皮病的研究进展

【摘要】 线状IgA大疱性皮病（LABD）是一种少见的自身免疫性表皮下水疱病。目前针对LABD的研究尚不完善,多为病例报道。本文综述LABD的病因和发病机制、临床及组织病理表现、诊断及治疗等方面的近期研究。     

自身免疫性疱病严重程度评分系统北大核心CSCD

自身免疫性疱病（AIBD）是一组少见的表现为皮肤红斑、水疱、大疱的皮肤病,不同程度地影响患者的生活质量。至今为止一直缺乏一个有效统一的评分系统来评估AIBD的疾病严重程度以及治疗效果,从而影响多中心对照研究。一项循证医学回顾研究表明,过去25年中天疱疮临床试验研究所涉及的评分方法近百种_2]。缺乏稳定、合理的评分系统使得治疗方案的对照研究不能有效进行,影响临床医生选择最佳的治疗方案。量化疾病严重程度不但能够判断病情预后,而且可以使同一患者不同治疗阶段以及不同患者之间进行对照研究,从而有效地评估治疗方案。本文将对自身免疫性疱病的病情评分系统进行较为详细的介绍。     

自身免疫性疱病严重程度评分系统

自身免疫性疱病（AIBD）是一组少见的表现为皮肤红斑、水疱、大疱的皮肤病,不同程度地影响患者的生活质量［1］。至今为止一直缺乏一个有效统一的评分系统来评估AIBD的疾病严重程度以及治疗效果,从而影响多中心对照研究。一项循证医学回顾研究表明,过去25年中天疱疮临床试验研究所涉及的评分方法近百种［２］。缺乏稳定、合理的评分系统使得治疗方案的对照研究不能有效进行,影响临床医生选择最佳的治疗方案。量化疾病严重程度不但能够判断病情预后,而且可以使同一患者不同治疗阶段以及不同患者之间进行对照研究,从而有效地评估治疗方案。本文将对自身免疫性疱病的病情评分系统进行较为详细的介绍……     

大疱性类天疱疮与2型炎症相关性的研究进展

大疱性类天疱疮(BP)是一种好发于老年人的自身免疫性水疱病。大部分大疱性类天疱疮患者有明显瘙痒症状,伴有血清总IgE、外周血嗜酸性粒细胞以及IL-4、IL-13等2型细胞因子水平升高。多种Th2相关炎症细胞及介质参与BP发病机制,其中Th2细胞及2型细胞因子是2型炎症反应的核心驱动因素,表明BP患者存在2型炎症反应。同时奥马珠单抗、度普利尤单抗成功治疗大疱性类天疱疮的案例进一步提示大疱性类天疱疮与2型炎症存在密切相关性。本文就大疱性类天疱疮与2型炎症的相关性作一综述。     

伴黏膜受累的成人线状IgA大疱性皮病1例并文献回顾

患者女,35岁,躯干、四肢红斑、瘙痒半月,加重伴水疱3 d。皮损组织病理示:表皮下水疱,疱液见中性粒细胞,真皮中浅层血管内及周围见中性粒细胞浸润;直接免疫荧光见IgA、IgG基底膜带线状沉积;根据临床表现、组织病理学、免疫荧光诊断为成人线状IgA大疱性皮病。线状IgA大疱性皮病为少见的自身免疫性表皮下大疱病,成人临床表现多样化,易出现误诊。     

表现为环状红斑水疱的自身免疫性表皮下水疱病25例回顾性分析

目的总结表现为环状红斑水疱的自身免疫性表皮下水疱病的临床、组织病理、免疫血清学及治疗特点。方法回顾性分析2015—2022年就诊于中国医学科学院皮肤病医院表现为环状红斑水疱的自身免疫性表皮下水疱病患者的资料。结果共纳入患者25例, 男10例、女15例, 年龄(39.21 ± 24.65)岁, 包括线状IgA大疱性皮病9例, 大疱性类天疱疮7例, 抗P200类天疱疮5例, 获得性大疱性表皮松解症4例, 20例(80%)有不同程度瘙痒。15例(60%)出现真皮组织嗜酸性粒细胞浸润, 11例(44%)外周血嗜酸性粒细胞计数增加, 7例(28%)同时有嗜酸性粒细胞组织浸润和外周血嗜酸性粒细胞升高。盐裂皮肤-间接免疫荧光及免疫印迹实验显示, 9例同时存在抗基底膜带IgG及IgA抗体, 包括4例大疱性类天疱疮、1例线状IgA大疱性皮病、2例抗P200类天疱疮、2例获得性大疱性表皮松解症;5例同时存在多种抗基底膜带靶抗原的抗体。7例大疱性类天疱疮均予系统糖皮质激素治疗, 其中5例联合免疫抑制剂, 2例联合米诺环素;线状IgA大疱性皮病、抗P200类天疱疮、获得性大疱性表皮松解症患者对抗炎药物及氨苯砜...     

大疱性类天疱疮患者血清及疱液中SOCS-1和SOCS-3的水平检测

目的：检测大疱性类天疱疮（BP）患者血清及疱液中细胞因子信号传导抑制蛋白1（SOCS-1）、细胞因子信号传导抑制蛋白3（SOCS-3）的表达水平。方法：收集我院2017年1月至2018年12月的大疱性类天疱疮患者，同时选取II度烫伤患者为对照组，ELISA法检测患者与对照血清及疱液中SOCS-1、SOCS-3表达水平，自身免疫性疱病严重程度评分（ABSIS）判定患者疾病严重程度。采用Pearson相关性分析法分析BP患者血清与疱液中SOCS-1、SOCS-3表达的关系及SOCS-1、SOCS-3水平与ABSIS的关系。结果：共收集42例BP患者和30例对照。BP患者血清SOCS-1和SOCS-3水平为62.14±12.45和47.23±10.72，高于对照组的31.25±9.85和20.62±9.06，差异具有统计学意义（均P＜0.05）；BP患者疱液中SOCS-1和SOCS-3水平为106.45±30.27和91.42±24.58，高于对照组的67.26±21.33和51.07±15.16，差异具有统计学意义（均P＜0.05）；BP患者SOCS-1与SOCS-3水平呈正相关（P＜0.05），SOCS-1和SOCS-3水平分别与ABSIS评分呈正相关（P＜0.05）。结论：大疱性类天疱疮患者血清及疱液中SOCS-1和SOCS-3表达水平升高，其表达水平与ABSIS评分呈正相关，可能与大疱性类天疱疮疾病的发病机制有关。     

Association between the subepidermal autoimmune blistering diseases linear IgA disease and the pemphigoid group and inflammatory bowel disease: two case reports and literature review

We report two patients with subepidermal autoimmune blistering diseases and inflammatory bowel disease (IBD) [one with linear IgA disease (LAD) and ulcerative colitis (UC), and the other with mucous membrane pemphigoid (MMP) and Crohn disease (CD)], and present a review of all previously reported cases. We reviewed the literature, and found 48 cases of patients with autoimmune blistering diseases and IBD. The blistering diseases were LAD (25 patients), bullous pemphigoid (BP) (21), MMP (1) and pemphigoid gestationis (1), while the IBD types comprised UC (40) and CD (8). We describe the clinical and immunopathological features and demographic characteristics of the patients. In all but one case, the diagnosis of IBD predated the development of the skin condition. The association was more common with LAD than BP. The immunopathogenesis of IBD and autoimmune blistering diseases is discussed and a link between them hypothesized, namely, that the presentation of multiple antigens to the immune system during the unregulated inflammation in the bowel wall results in excitation of the immune system and recognition of autologous antigens.     

B‐cell activating factor detected on both naïve and memory B cells in bullous pemphigoid

B‐cell activating factor (BAFF), an important immune regulatory cytokine, is involved in development of autoimmune diseases. Although BAFF is expressed in various cells, including dendritic cells (DCs) and monocytes, BAFF expression on B cells has not been well documented. In the present study, BAFF molecules on DCs and naïve and memory B cells in autoimmune bullous diseases, including pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid (BP), were analysed by flow cytometry. Compared with healthy controls (HC), BAFF expression on naïve and memory B cells increased significantly in BP. No difference in BAFF receptor expression in naïve and memory B cells was shown among all study groups. Furthermore, BAFF expression in both naïve and memory B cells of BP, but not HC, was detected by confocal microscopic analysis. These results implied that BAFF expressed by B cells may play a pathogenic role in autoimmune bullous diseases, particularly BP.     

Bullous Pemphigoid in a Renal Transplant Recipient

Bullous pemphigoid (BP) is an autoimmune disease with chronic, recurrent bullous eruptions. BP has been reported to be associated with drugs, physical stimuli, malignancies, and immune abnormalities. Its association with renal transplant is rare and only four cases have been reported. We present a case of BP in a 52-year-old man with chronic hepatitis B and C infection who underwent a cadaveric renal transplant 13 years earlier. His graft was still functioning well when BP appeared. The occurrence of BP in our patient might be a result of drugs (furosemide or tacrolimus), viruses, or renal allograft. As the patient was receiving regular T-cell immunosuppressant therapy, his BP lesions were recalcitrant to corticosteroid treatment. We discuss the pathogenesis and treatment of such patients.     

BP180‐ and BP230‐specific IgG autoantibodies in pruritic disorders of the elderly: a preclinical stage of bullous pemphigoid?

Pruritus increasingly occurs in the elderly population and is associated with a variety of dermatoses of mixed aetiology. Clinical and experimental evidence suggests that senile pruritus may be linked to autoimmune events initiated by loss of self‐tolerance against cutaneous autoantigens, which is facilitated by immune ageing processes. T‐cell immunity, which underpins the production of pathogenic autoantibodies in autoimmune diseases, is deregulated by immune senescence thereby leading to autoimmune disorders such as bullous pemphigoid (BP). High mortality rates of BP combined with steadily increasing incidence emphasize the need for an effective diagnostic strategy at an early stage. We summarize here the current understanding of immunological alterations during the ageing process, thereby focusing on aberrant T‐cell responses against the basement membrane antigens BP180 and BP230, which may eventually lead to the clinical outcome of BP.     

High-dose intravenous immune globulin for the treatment of autoimmune blistering diseases: an evaluation of its use in 14 cases

High-dose intravenous immune globulin (IVIG) is used to treat a wide variety of autoimmune diseases. We report our experiences of its use in a retrospective study of 14 patients with autoimmune blistering diseases, namely epidermolysis bullosa acquisita (EBA), two; bullous pemphigoid (BP), two; pemphigoid gestationis (PG), one; nodular pemphigoid, two; and pemphigus vulgaris (PV), seven. Two patients with refractory EBA improved following regular courses of IVIG given as monotherapy. IVIG had a steroid-sparing effect in 10 patients with PV, BP and PG. However, the clinical effects were transient and of variable intervals, and repeated courses of IVIG were required. The rapid actions of IVIG were of particular benefit in two patients with extensive, rapidly progressive PV and in one patient with BP in whom swift disease control was required. In such cases, when rapid disease control is paramount, we recommend IVIG used in conjunction with conventional treatments as a safer and less invasive alternative to plasmapheresis. IVIG was ineffective in two patients with nodular pemphigoid. Analysis of indirect immunofluorescence (IIF) titres before and after IVIG showed that a fall in titre occurred after 78% of treatments and was observed in all disease groups. However, like the clinical improvements, the falls in IIF titres were transient and of variable interval, and titres rose back to pretreatment levels in all but one patient. IVIG appears to be beneficial under certain circumstances for the treatment of autoimmune blistering diseases but controlled trials are required to define its therapeutic role further.     

Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma

Therapeutic immune checkpoint blockade for metastatic melanoma has been associated with vitiligo, pruritus and morbilliform eruptions. Reports of other autoimmune skin disease in this setting are rare. We sought to expand the spectrum of cutaneous immune‐mediated effects related to immune checkpoint inhibitor therapy. In this report, we describe two unusual cutaneous reactions related to checkpoint inhibitor therapy, namely bullous pemphigoid (BP) and dermatitis herpetiformis. The development of BP and dermatitis herpetiformis in the context of checkpoint inhibitor therapy is consistent with previous investigations supporting the importance of effector and regulatory T cells in the pathogenesis of these diseases.     

IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis

BACKGROUND: Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. OBJECTIVES: We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. METHODS: Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180. RESULTS: All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180. CONCLUSIONS: The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.     

Rituximab in autoimmune bullous diseases: mixed responses and adverse effects

BACKGROUND: Intolerably high doses of systemic corticosteroids and additional immunosuppressants may be required to control disease activity in autoimmune bullous skin diseases. New therapeutic options are needed for such patients. OBJECTIVES: To determine the efficacy and adverse effects of adjuvant rituximab. METHODS: Seven patients with refractory autoimmune blistering diseases (pemphigus vulgaris, PV, n = 4; bullous pemphigoid, BP, n = 2; mucous membrane pemphigoid, MMP, n = 1) were treated four times with rituximab at an individual dose of 375 mg m(-2) at weekly intervals. RESULTS: All lesions cleared in three patients (two PV, one BP), while they were reduced by more than 50% in three others (two PV, one BP). The concomitant immunosuppressive medication was reduced in five patients (four PV, one BP). The patient with MMP developed bilateral blindness while nasopharyngeal lesions resolved. Three patients (two BP, one PV) experienced severe adverse events including fatal pneumonia. CONCLUSIONS: Adjuvant B-cell depletion by rituximab is effective in otherwise therapy-resistant bullous autoimmune disorders but may be associated with substantial adverse effects including fatal outcomes.     

Bullous pemphigoid in adolescence

Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting the elderly but is quite rare in childhood. The majority of pediatric cases have been reported during early childhood. Adolescence is divided into three phases: early (10‐13 years), middle (14‐17), and late (18‐21). This review aimed to identify BP cases in adolescence and demonstrate their clinical features and course. Our literature search was performed in Medline with the terms “bullous pemphigoid in childhood and adolescence,” “childhood bullous pemphigoid,” “juvenile bullous pemphigoid,” and “autoimmune blistering and autoimmune bullous diseases in childhood.” The data extraction for late adolescence was limited by the fact that this age group is included in adult BP registries. We identified nine cases in early adolescence. Mucosa were affected in 5 of 9 cases. Treatment consisted of systemic prednisone (8/9), in combination with dapsone (2/9), azathioprine (2/9), or erythromycin/nicotinamide (1/9). Relapses were reported in 3 of 9 cases. We identified five cases occuring in middle adolescence. Mucosa were not affected. Treatment consisted of systemic prednisone (5/5), in combination with dapsone (3/5), azathioprine (2/5), doxycycline/nicotinamide (1/5), or mycophenolate mofetil (1/5). Relapses were reported in two of five cases. No case of BP in the late adolescence was included in the results, as only one case met the search criteria, and overlapped with pemphigus vulgaris. With only 14 cases found in our review, BP in adolescence appears even rarer than in earlier childhood. Despite its low prevalence, BP should be included in the differential diagnosis of autoimmune blistering diseases in adolescents.