药物诱发自身免疫性水疱病的研究进展

在特定基因背景下由药物诱发的自身免疫性水疱病(autoimmune bul-lous dermatoses,AIBD),称为药物相关AIBD.临床上最常见的药物相关AIBD包括天疱疮、大疱性类天疱疮和线状IgA大疱性皮病.本文对三种最常见的药物相关AIBD进行综述,主要阐述了引起发病的相关药物、临床表现和治疗方面的进展...     

成人线状IgA大疱性皮病5例临床分析

目的：了解5例成人线状IgA大疱性皮病的临床特点,以提高对该病的认识。方法：对5例成人线状IgA大疱性皮病的临床资料、组织病理、免疫荧光进行分析,并对相关文献进行复习。结果：5例患者中男3例,女2例,年龄在66—87岁之间,均表现为在红斑基础上的水疱,或外观正常的皮肤上出现的水疱,病理组织活检和免疫荧光确诊为成人线状IgA大疱性皮病。结论：成人线状IgA大疱性皮病好发年龄为〉60岁的老年人,皮疹表现类似大疱性类天疱疮、疱疹样皮炎,多数兼有两病的特点,容易误诊,直接免疫荧光检查发现沿基底膜带有均质型线状IgA沉积具有诊断价值。     

线状IgA大疱性皮病15例分析

目的分析线状IgA大疱性皮病的临床特点、治疗及预后,提高临床医生对本病的认识。方法回顾性分析本科2004年1月-2011年12月诊治的15例线状IgA大疱性皮病的临床资料。结果男6例,女9例;儿童型5例,成人型10例;皮损初始部位:面部4例,口腔黏膜及双下肢各3例;累及躯干和四肢12例,14例临床表现为红斑或正常皮肤上出现水疱,6例水疱呈环形或半环形排列。皮损组织病理均见表皮及复层鳞状上皮下水疱或裂隙,直接免疫荧光均表现为基底膜带线状IgA沉积。13例予糖皮质激素治疗,皮损均控制;2例予氨苯砜治疗,均发生不良反应。结论线状IgA大疱性皮病的皮损以口腔黏膜、面部及下肢首发居多,好发于躯干和四肢,临床表现为红斑或正常皮肤上出现水疱,呈孤立、环形和/或半环形排列;组织病理可见表皮或复层鳞状上皮下水疱或裂隙,直接免疫荧光示基底膜带线状IgA沉积是诊断的主要依据。治疗上可选用氨苯砜、糖皮质激素和磺胺类药物等。     

成人线状IgA大疱性皮病1例

患者女,43岁。面颈部及躯干反复出现红斑和水疱7月。皮肤科情况:面颈部及躯干泛发水肿性红斑、丘疹和张力性小水疱,呈环状排列。皮损组织病理示:表皮下水疱,疱内及真皮可见大量嗜酸性粒细胞浸润,真皮层有少许中性粒细胞等炎性细胞浸润。直接免疫荧光见基底膜带IgA呈线状沉积。诊断:成人线状IgA大疱性皮病。予氨苯砜治疗2周,起效快,疗效好。     

成人面部线状IgA大疱性皮病一例

临床资料患者,男,28岁。主因面部反复出现红斑、水疱伴瘙痒6年,加重10d,于2012年1月31日就诊。     

寻常性银屑病并发成人型线状IgA大疱性皮病

报告l例寻常性银屑病并发成人型线状IgA大疱性皮病.患者男,36岁.因全身红色斑疹伴白色鳞屑反复发生20年.躯干、双上肢出现环状排列的水疱10d伴瘙痒就诊.皮损组织病理检查:表皮下水疱,疱内、真皮浅层和真皮乳头见中性粒细胞、嗜酸性粒细胞浸润;皮损周围皮肤直接免疫荧光显示基膜带Iga、IgG呈带状沉积;取患者血清行BP180NC16A(大疱性类天疱疮18 000抗原的近膜片段)-ELISA检查显示阴性;以盐裂正常人皮肤为底物,取患者血清行间接免疫荧光检查显示IgA、IgG呈带状沉积在真皮侧.诊断为寻常性银屑病并发成人型线状TgA大疱性皮病.     

人源性抗大疱性类天疱疮抗原BP180-NC16A单链抗体的构建及表达

目的用基因工程技术制备人源性抗大疱性类天疱疮抗原BP180单链抗体(scFv),并对其抗原结合特异性等进行鉴定。方法利用基因重组技术对从噬菌体抗体库中克隆的人源性抗大疱性类天疱疮抗原BP180-NC16A抗体Fab片段进行改造获得scFv,进行DNA测序,同时用ELISA法鉴定其抗原结合活性和特异性,免疫荧光技术检测scFv与人皮肤组织BP180抗原的结合情况。结果成功构建了抗BP180-NC16A scFv,并获得可溶性表达,DNA测序结果表明,单链抗体的Vλ和VH基因序列完全正确,ELISA法证实可溶性表达的scFv抗体具有良好的抗原结合活性和特异性。免疫荧光检测该抗体在人皮肤表皮、真皮交界处基底膜带呈现线状结合条带。结论成功构建并表达了人源性抗大疱性类天疱疮抗原BP180-NC16A的单链抗体,为进一步研究该抗体的生物学作用奠定了基础。     

儿童型线状IgA大疱性皮病一例

患儿女,7岁,主因全身起水疱伴剧痒1月余入院。皮科情况：全身见较多红色斑片、丘疹、丘疱疹及水疱,部分水疱呈腊肠样,水疱主要分布于红斑边缘。水疱破后形成糜烂伴结痂。以面、臀及股内侧较密集,部分表面可见浆痂。病理：表皮下水疱,疱内可见散在嗜中性粒细胞,疱底及疱两侧表皮可见大量嗜中性粒细胞,偶见嗜酸性粒细胞。免疫荧光检查：DIF：IgA 弱阳性,IgG 阳性,IIF：IgA 阴性。诊断：儿童型线状IgA大疱性皮病。治疗：氨苯砜,100mg/天,10余天后基本痊愈,至今40余天,皮疹无复发。讨论：线状IgA大疱性皮病(LABD)由Chorzelski ( 1979)首先命名。本例患儿发病早、具特征性皮损,HE病理：表皮下水疱,疱内可见散在嗜中性粒细胞,疱底及疱两侧表皮可见大量嗜中性粒细胞。免疫荧光可见IgG、IgA于基底膜带呈线状沉积。氨苯砜治疗效果好,儿童型线状IgA大疱性皮病诊断成立。本例免疫病理IgA、IgG均阳性,提示该患儿是否可能存在IgA大疱性皮病与大疱性类天疱疮的重叠,还有待于进一步检查。     

成人线状IgA大疱性皮病2例

报道2例成人线状IgA大疱性皮病。患者1,女,57岁。躯干、四肢红斑、水疱2个月,伴痒。皮肤科检查:躯干、四肢水肿性红斑,呈环形,部分边缘可见黄豆粒大水疱,疱液清,尼氏征阴性。患者2,女,43岁。躯干、四肢散发性水疱20天,伴痒。皮肤科检查:躯干、四肢绿豆至黄豆大水疱,疱液清,尼氏征阴性。两例患者组织病理检查均表现为:表皮下水疱,真皮乳头嗜中性粒细胞小脓肿;直接免疫荧光示:表皮基底膜带IgA线状沉积。     

Immunofluorescence testing in the diagnosis of autoimmune blistering diseases: overview of 10-year experience

BACKGROUND

Immunofluorescence testing is an important tool for diagnosing blistering diseases.

OBJECTIVE

To characterize the immunofluorescence findings in patients diagnosed with autoimmune blistering skin diseases.

METHODS

We retrospectively analyzed immunofluorescence results encompassing a 10-year period.

RESULTS

421 patients were included and divided into 2 groups: group 1- intraepidermal blistering diseases (n=277) and 2- subepidermal blistering diseases (n=144). For group 1, positive DIF findings demonstrated: predominance of IgG intercellular staining (ICS) and C3 for pemphigus foliaceus-PF (94% and 73% respectively), pemphigus vulgaris-PV (91.5%-79.5%) and paraneoplastic pemphigus-PNP (66%-33%); ICS IgA in 100% of IgA pemphigus cases, and IgG deposits in the basement membrane zone (BMZ) along with ICS in one Hailey-Hailey patient. The IIF findings revealed mean titers of 1:2.560 for PV and 1:1.280 for PF. For paraneoplastic pemphigus, IIF was positive in 2 out of 3 cases with rat bladder substrate. In group 2, positive DIF findings included multiple deposits at basement membrane zone for epidermolysis bullosa acquisita-EBA (C3-89%,IgG-79%,IgA-47%,IgM-21%) mucous membrane pemphigoid-MMP (C3,IgG,IgA,IgM-80%) and bullous pemphigoid-BP (C3-91%,IgG-39%,IgA-11%,IgM-6%), and IgA at basement membrane zone for IgA linear disease (99%) and dermatitis herpetiformis-DH (dermal papillae in 84.6%). For lichen planus pemphigoides, there was C3 (100%) and IgG (50%) deposition at basement membrane zone. indirect immunofluorescence positive findings revealed basement membrane zone IgG deposits in 46% of BP patients, 50% for EBA, 15% for IgA linear dermatosis and 50% for LPP. Indirect immunofluorescence positive results were higher for BP and EBA with Salt-Split skin substrate.

CONCLUSION

Our results confirmed the importance of immunofluorescence assays in diagnosing autoimmune blistering diseases, and higher sensitivity for indirect immunofluorescence when Salt-split skin technique is performed.     

Corticosteroid use in autoimmune blistering diseases

Corticosteroids, while providing rapid remission and ongoing control of symptoms of autoimmune blistering diseases (AIBD), have numerous potentially serious acute and long-term side effects. Evidence-based medicine has reevaluated the various types of corticosteroids and forms of corticosteroid delivery in AIBD to ascertain whether any advantages of specific delivery systems or regimens exist. Careful monitoring of patients and simple preventive measures are effective in minimizing the adverse outcomes associated with their use. This article outlines the current level of evidence for corticosteroid use in AIBDs, and discusses appropriate investigations and interventions to minimize or prevent the associated adverse effects.     

大疱性类天疱疮和妊娠疱疹患者血清抗BP180 NC16A抗体的纯化和鉴定

目的 探讨大疱性类天疱疮（BP）和妊娠疱疹（HG）患者血清抗BPl80 NC16A 抗体的纯化和鉴定方法。方法 原核表达系统pGEX-2TBP180NC16A表达GST/NC16A融合蛋白,将融合蛋白与谷胱甘肽琼脂糖凝聚微珠进行共价偶联。微珠亲和层析法纯化BP和HG患者血清中抗BP180 NC16A抗体,并用ELISA、免疫荧光、及Western印迹进行鉴定。结果 原核表达系统pGEX-2TBP180NC16A表达37 000 GST/NC16A融合蛋白,微珠亲和层析法纯化后得单一抗BP180 NC16A抗体。经ELISA方法定量后确定其含量为2.4 mg/ml;该抗体能与人皮肤基底膜带结合,证明抗体活性;免疫印迹可见单一片段,显示抗体纯度。结论 微珠亲和层析法纯化的BP和HG患者血清中抗BP180 NC16A自身抗体活性高、特异性强。     

Approach to the patient with autoimmune mucocutaneous blistering diseases

Autoimmune mucocutaneous blistering diseases (AMBD) are a rare group of dermatoses that can be potentially fatal. There are many subtypes and their clinical presentation can vary from being localized to general involvement. It is crucial that a diagnosis be made as early as possible and appropriate treatments are implemented. This article will discuss the diagnosis and available treatments of the major AMBDs. There are very few case-controlled studies regarding the treatments of these diseases. Most of the treatments used for these diseases are based on anecdotal reports. Hence, a synopsis of the conventional treatments and some brief recommendations will also be discussed. A brief discussion regarding "rescue" therapies that have been used for those patients with more recalcitrant cases of AMBD will also be presented.     

BP180NC16a-ELISA对大疱性类天疱疮血清学诊断的评价

目的 评价BP180NC16a-ELISA对大疱性类天疱疮血清学诊断的效能.方法 BP患者42例,对照组42例(其中正常人对照24例,天疱疮18例),在患者用药前采血,比较BP180NC16a-ELISA和盐裂试验免疫荧光(IIF)检测的结果.结果 用BP180NC16a-ELISA检测时,BP患者中有1例呈阴性反应,其敏感性为97.62%;正常人对照组中有1例呈阳性反应,其特异性为97.62%,且BP180NC16a-ELISA法的A值与IIF滴度之间无相关性.结论 BP180NC16a-ELISA在疾病初始阶段是检测血清中抗BP180抗体的有效方法.     

大疱性类天疱疮与瘢痕性类天疱疮

通过大疱性类天疱疮与瘢痕性类天疱疮之间的比较,发现大疱性类天疱疮与瘢痕性类天疱疮之间存在相关性,表现在好发人群均为老年人、存在相同致病抗体、两者可同时合并肿瘤、间接免疫荧光显示致病抗体沉积在表皮侧等方面。近年来生物制剂如抗CD20抗体利妥昔等应用于大疱性类天疱疮与瘢痕性类天疱疮的临床治疗,具有一定疗效。瘢痕性类天疱疮的黏膜受累机制与大疱性类天疱疮180及层粘连蛋白332等自身抗体有关,发病机制尚待进一步研究。     

IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis

Please cite this paper as: IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis. Experimental Dermatology 2010; 19: 648–653. Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120‐kDa protein which is highly homologous to a shedded fragment of the BP180‐ectodomain. Objectives: The aim of our study was to determine the incidence of IgA autoantibodies directed against BP180/BP230 in the pemphigoids and LABD and to determine the antigenic regions that are targeted by IgA autoantibodies. Methods: Utilizing baculovirus‐expressed recombinant BP180 and BP230 proteins, we performed immunoblot analyses for IgA reactivity of sera from patients with BP (n = 30), MMP (n = 10), PG (n = 6), LABD (n = 6) and from control patients with non‐related pruritic dermatoses (n = 8). Results: IgA reactivity against BP180 and/or BP230 was detected in 19/30 of the BP, in 7/10 of the MMP, in 6/6 of the LABD and in 3/6 of the PG sera, respectively, but not in the control group. In all subgroups, the major antigenic site recognized by IgA antibodies was located within the NH₂‐terminus of the BP180‐ectodomain, but only a minority of the sera showed also IgA reactivity against the BP180‐NC16a‐domain. IgA reactivity against the central domain of BP180 was more frequently seen than against its COOH‐terminus. IgA against the COOH‐ and NH₂‐terminus of BP230, respectively, was detected in 6/30 of the BP, 1/10 of the MMP, 1/6 of the LABD and 0/8 control sera. Conclusion: IgA reactivity against BP180 and/or BP230 is a common finding in the pemphigoids.     

自身免疫性表皮下大疱病诊疗共识（2022）

【摘要】 自身免疫性表皮下大疱病主要包括大疱性类天疱疮、黏膜类天疱疮、瘢痕性类天疱疮、妊娠类天疱疮、扁平苔藓类天疱疮、线状IgA大疱性皮病、获得性大疱性表皮松解症、抗p200/层黏连蛋白γ1类天疱疮及疱疹样皮炎,不同的疾病靶抗原和致病性自身抗体存在差异,临床表现有相似之处也有明显不同,诊断与鉴别诊断有赖临床、病理、免疫病理检查及血清抗体检测等。为规范此类疾病的临床诊疗,中华医学会皮肤性病学分会和中国医师协会皮肤科医师分会组织本领域专家,依据近年国内外临床研究数据和指南共识,制订本共识 。     

Management of autoimmune blistering diseases in pregnancy

Autoimmune blistering disease (AIBD) in pregnancy raises several complex management issues associated with underlying pathogenesis and treatment options. This article considers the effects of the disease as well as its treatment for both mother and fetus. All AIBDs can occur in pregnancy but are relatively rare. Pemphigoid gestationis is a rare AIBD that is specific to pregnancy. The article considers each AIBD in turn and then looks at treatment options for the group as a whole, as there are many issues common to all.     

Childhood bullous pemphigoid associated with IgA antibodies against BP180 or BP230 antigens

Linear IgA bullous dermatosis (LABD) comprises a heterogeneous group of subepidermal blistering disorders characterized by in situ bound IgA antibodies in epidermal basement membrane. We report three children presenting clinical and immunopathological features characteristic of LABD. By immunoblotting, the three patients' sera contained IgA antibodies that reacted against the bullous pemphigoid (BP) antigen 180 and or BP230, molecular markers for BP. In addition, IgG antibodies directed against the ectodomain of BP180 were detected by an enzyme-linked immunosorbent assay using a eukaryotic recombinant form of BP180. Consistent with recent studies suggesting that the LABD antigen 1, the predominant autoantigen of LABD, is either a proteolytic product of BP180 or an isoform of the BP180 gene, our findings indicate that a subset of children with features of LABD have a distinct form of BP associated with an IgA response.