BP180相关自身免疫性水疱病的研究进展

BP180相关自身免疫性水疱病包括大疱性类天疱疮、扁平苔藓样类天疱疮、线状IgA大疱性皮病、妊娠类天疱疮和瘢痕性类天疱疮。BP180胞外区含有多个自身抗体反应的位点,目前研究显示,BP180上相关自身免疫性水疱病靶位呈现出异质性,并且同一种疾病不同临床表现也与靶位异质性有关,然而异质性机制仍有待于进一步研究和探讨。     

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 。     

Autoimmune bullous diseases in pregnancy: clinical and epidemiological characteristics and therapeutic approach

Autoimmune bullous dermatoses are a heterogeneous group of diseases with autoantibodies against structural skin proteins. Although the occurrence of autoimmune bullous dermatoses during pregnancy is low, this topic deserves attention, since the immunological and hormonal alterations that occur during this period can produce alterations during the expected course of these dermatoses. The authors review the several aspects of autoimmune bullous dermatoses that affect pregnant women, including the therapeutic approach during pregnancy and breastfeeding. Gestational pemphigoid, a pregnancy-specific bullous disease, was not studied in this review.     

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.     

获得性大疱性表皮松解症伴宫颈鳞状细胞癌一例

患者女,54岁,因反复眼干涩2年,躯干四肢水疱伴口腔破溃2个月入院.皮肤科检查:鼻腔黏膜破溃结痂、充血.口腔大片浅溃疡,可见有水疱,表层水肿发白,边缘充血,下唇散在小溃疡,双峡颊黏膜水肿,溃疡与舌背相似.肩部、颈部及躯干见红斑周围或红斑上散在少许水疱,疱壁稍紧张,疱壁薄,尼氏征可疑阳性.该例以黏膜为突出表现,临床表现类似于瘢痕性类天疱疮,容易误诊,且皮疹和黏膜损害随着肿瘤的病情而转变.获得性大疱性表皮松解症与Ⅶ胶原有关,可能与恶性肿瘤及鳞状细胞癌有一定的相关性.     

Quality of life index in autoimmune bullous dermatosis patients

BACKGROUND

Autoimmune bullous dermatoses are complex diseases triggered by autoantibodies action against epidermal antigens or the dermoepidermal junction. Blisters and vesicles that evolve with erosion areas characterize them. Although rare, they present high morbidity, affecting the quality of life of patients.

OBJECTIVES

To assess the magnitude of autoimmune bullous dermatoses on life quality of patients treated in a public university service in countryside of Brazil.

METHODS

This cross-sectional study was based on an inquiry with autoimmune bullous dermatoses patients assisted at outpatient university referral service. Elements related to quality of life were evaluated by the Dermatology Life Quality Index, as well as clinical and demographic data.

RESULTS

The study evaluated 43 patients with pemphigus foliaceus, 32 with pemphigus vulgaris, 6 with bullous pemphigoid and 3 with dermatitis herpetiformis. The average age was 48 ± 16 years and 34 (40%) were female. The median score (p25-p75) of the Dermatology Life Quality Index was 16 (9-19), classified as "severe impairment" of life quality, in which the greater impact was related to symptoms and feelings, daily and leisure activities.

CONCLUSIONS

Autoimmune bullous dermatoses inflict severe impairment of quality of life for patients followed by a public outpatient clinic in the countryside of Brazil.     

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.     

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.     

Scanning electron microscopy of a blister roof in dystrophic epidermolysis bullosa

In dystrophic epidermolysis bullosa the genetic defect of anchoring fibrils leads to cleavage beneath the basement membrane, with its consequent loss. We performed scanning electron microscopy of an inverted blister roof of a case of dystrophic epidermolysis bullosa, confirmed by immunomapping and gene sequencing. With a magnification of 2000 times a net attached to the blister roof could be easily identified. This net was composed of intertwined flat fibers. With higher magnifications, different fiber sizes could be observed, some thin fibers measuring around 80 nm and thicker ones measuring between 200 and 300 nm.     

Bullous pemphigoid in a 3-month-old infant: case report and literature review of this dermatosis in childhood

Bullous pemphigoid is an autoimmune subepidermal blistering dermatosis that is uncommon in childhood. We report a case of a female infant, 3 months old, which presented clinical and laboratory data for the confirmatory diagnosis of bullous pemphigoid. The authors used immunohistochemical staining for collagen type IV that allowed the differentiation of bullous pemphigoid from other subepidermal bullous diseases. Opportunely we review the clinical, immunological, therapeutic and prognostic features of this pathology in children.     

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.     

Recommendations for the use of immunoapheresis in the treatment of autoimmune bullous diseases

Despite the use of high‐dose systemic corticosteroids in combination with other immunosuppressants, in some patients with autoimmune bullous diseases only insufficient improvement is achieved. In these cases and in acute severe disease, adjuvant immunoapheresis has been increasingly used. A consensus meeting was held in mid‐2005 in Hamburg, aiming at developing guidelines for the use of immunoapheresis in the treatment of autoimmune bullous diseases.This paper summarizes the experts‘ recommendations.     

Spectrum of subepidermal immunobullous disorders seen at the National Skin Centre,Singapore: a 2-year review

BACKGROUND: The subepidermal immunobullous disorders (SEIBDs) comprise bullous pemphigoid (BP), cicatricial pemphigoid (CP), epidermolysis bullosa acquisita (EBA), linear IgA disease (LAD), dermatitis herpetiformis (DH), pemphigoid gestationis (PG) and bullous systemic lupus erythematosus (BSLE). They are thought to be rarer in the Far East than in western Europe. OBJECTIVE: This 2-year retrospective study investigates the spectrum seen at our centre and the minimum estimated incidence of each. PATIENTS AND METHODS: A total of 67 patients seen at the National Skin Centre (NSC), Singapore between January 1998 and December 1999 were diagnosed as having an SEIBD. Fifty-nine (88%) had BP, four (6%) had EBA, two (3%) LAD and two (3%) BSLE. There were no cases of CP, DH or PG diagnosed during this period. The minimum estimated incidence in our local population was 7.6, 0.5, 0.26 and 0.26 per million population per year, respectively. The mean age of onset was 77, 68, 65 and 31 years, respectively. RESULTS: BP is the commonest SEIBD seen locally, with an incidence at least equal to that in western Europe. It is diagnosed at our centre three times more frequently than pemphigus. There is a predilection for ethnic Chinese but not Indian. EBA is twice as common as in western Europe and shows a predilection for ethnic Indians. LAD is rare here compared to China, despite the predominant Chinese population. BSLE is also rare. In contrast to western Europe, CP, DH and PG are very rare in Singapore. CONCLUSIONS: This is the first study from this region to show that certain SEIBDs are not rarer in the Far East, as previously thought.     

Clinical study of skin changes in low and high risk pregnant women

BACKGROUND

During pregnancy there is immunological, metabolic, endocrine and vascular changes responsible for physiological and pathological skin changes.

OBJECTIVES

determine the prevalence of specific physiological changes and pregnancy, comparing the period of gestation of their appearances and compare type of prenatal care as the skin changes.

METHODS

A cross-sectional study with 905 pregnant women.

RESULTS

The prevalence of physiological skin changes was 88.95% and the most common was pigment. The prevalence of specific dermatoses was 8.72% and atopic eruption was the most common.

CONCLUSION

Physiological changes were seen more in the 3rd quarter, as well as the specific dermatoses. No statistical difference in prenatal low risk compared to high risk was observed, whereas the cutaneous physiological changes and specific pregnancy dermatoses.     

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.     

Japanese guidelines for the management of pemphigoid (including epidermolysis bullosa acquisita)

The pemphigoid group is a category of autoimmune subepidermal blistering diseases in which autoantibodies deposit linearly at the epidermal basement membrane zone (BMZ). The main subtypes of pemphigoid mediated by immunoglobulin G autoantibodies are bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). To establish the first guidelines approved by the Japanese Dermatological Association for the management of pemphigoid diseases, the Committee for Guidelines for the Management of Pemphigoid Diseases (Including EBA) was founded as part of the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labor and Welfare Research Project on Overcoming Intractable Diseases. These guidelines aim to provide current information for the management of BP, MMP and EBA in Japan. Based on evidence, the guidelines summarize the clinical and immunological manifestations, pathophysiologies, diagnostic criteria, disease severity determination criteria, treatment algorithms and treatment recommendations. Because of the rarity of these diseases, there are few clinical studies with a high degree of evidence, so several parts of these guidelines were established based on the opinions of the Committee. To further optimize these guidelines, periodic revision in line with the new evidence is necessary.     

不同底物间接免疫荧光对自身免疫性表皮下水疱病诊断的评价

目的评价以正常人皮肤、猴食管及盐裂皮肤为底物的间接免疫荧光对自身免疫性表皮下水疱病的诊断价值。方法选取2015年1月至2016年12月在中国医学科学院皮肤病研究所诊断的自身免疫性表皮下水疱病56例,其中大疱性类天疱疮(BP)47例,获得性大疱性表皮松解症(EBA)6例,线状IgA大疱性皮病2例,P200类天疱疮1例。对照组为70例天疱疮、15例慢性湿疹和15例健康成人。分别以正常人皮肤、猴食管及盐裂皮肤为底物行间接免疫荧光,观察荧光沉积情况,比较不同表皮下水疱病间接免疫荧光检测的敏感性和特异性。采用SPSS 13.0软件,计数资料比较采用χ^2检验。结果BP患者血清以正常人皮肤、猴食管为底物间接免疫荧光可见到荧光物质沿基底膜带线性沉积,盐裂皮肤间接免疫荧光可见BP患者荧光线性沉积于表皮侧,EBA和P200类天疱疮线性沉积于真皮侧。以正常人皮肤、猴食管及盐裂皮肤为底物间接免疫荧光对表皮下水疱病诊断的敏感性分别为73.2%、60.7%、94.6%,差异有统计学意义(χ^2=18.2,P<0.05),特异性分别为98.0%、100%、97.1%,差异无统计学意义(P >0.05),以盐裂皮肤为底物时诊断的敏感性高于以正常人皮肤、猴食管为底物(χ^2值分别为8.0、16.7,均P<0.05)。结论对于自身免疫性表皮下水疱病的诊断,盐裂皮肤为底物行间接免疫荧光检查优于以猴食管和正常人皮肤为底物。     

免疫球蛋白E型自身抗体在自身免疫相关皮肤病中的研究进展

大量研究显示,免疫球蛋白E(IgE)不但参与变态反应的发生发展,还可通过多种机制诱发和加重自身免疫反应.IgE型自身抗体已证实可在多种自身免疫相关皮肤病中出现,可能通过与自身抗原结合影响树突细胞、肥大细胞、嗜碱性粒细胞等多种免疫机制参与相关疾病的发生发展.本文综述IgE在系统性红斑狼疮、大疱性类天疱疮以及慢性特发性荨麻...     

胸腺基质淋巴细胞生成素在不同皮肤病中的作用机制研究

【摘要】 胸腺基质淋巴细胞生成素（TSLP）是一种与白细胞介素7（IL-7）类似的细胞因子,可以促进多种细胞的分化和增殖,并使其分泌Th2细胞因子,在机体免疫系统中发挥重要作用。近年来发现在许多皮肤病中TSLP的表达水平异常,在部分皮肤病中其水平高低还与疾病严重程度相关,提示TSLP可能是治疗多种皮肤病的潜在靶点。本文综述近年来TSLP在多种皮肤病（包括炎症性疾病、免疫性疾病、遗传性疾病和肿瘤性疾病）发生发展中的研究进展,为临床相关疾病的诊治提供依据和思路。     

Management of autoimmune bullous diseases in France: a nationwide network of 30 centers

Limited data are available on the epidemiology of autoimmune bullous diseases in France and in Western Europe. Bullous pemphigoid represents the most common autoimmune bullous disease. The management of autoimmune bullous diseases in France is under the guidance of dermatologists. In 1985, a research group focused on autoimmune bullous diseases was created in France. In 2004, the French Ministry of Health established and funded a nationwide network including 2 references centers, 7 competence centers, and 30 corresponding centers, with the aim of improving quality of care and research for autoimmune bullous diseases.