51例表皮下大疱性疾病临床结合病理的研究

作者对51例表皮下大疱性疾病即大疱性类天疱疮(BP)、疱疹样皮炎(DH)和大疱性多形红斑(BEM)的组织学特点结合临床表现(包括病程和疗效)进行了回顾分析。这3种疾病的临床和组织学诊断标准如下:1.BP,多见于年龄较大者,皮损表现为大而紧张的大疱,常有出血和糜烂,呈泛发性分布,可有瘙痒,本病对小剂量皮质类固醇治疗有满意的疗效,痊愈后留有瘢痕和色素沉着。组织学检查显示单房性大疱,基底膜位于大疱的底部;真皮乳头内有花彩状结构但无小脓肿形成;真皮内一般有轻度炎症浸润,大疱上面的表皮偶有坏死。2.DH,多见于年龄较轻者,皮损表现为集簇性的小丘疹、丘疱     

寻常型银屑病伴寻常型天疱疮2例

临床资料 例1男,60岁.因全身潮红、脱屑冰疱、糜烂伴痒20天,于2006年10月12日人院.该患者有银屑病史20年,间断口服迪银片及私人配制的中药控制皮损.20天前因上呼吸道感染,银屑病皮损泛发,在我院门诊给予阿奇霉素静点,维胺酯胶囊口服,皮损减轻,但全身逐渐出现水疱、大疱,疱壁薄,易破溃,破后形成糜烂面.故人院治疗.     

系统性红斑狼疮中的大疱病

本文报告3例伴发水疱性皮损的系统性红斑狼疮(SLE)女性患者,患者均有心包炎、胸腔积液、肾小球肾炎、关节炎及面颊部盘状红斑.例2、例3水疱仅限于面部;例1则有泛发性小、大疱风团和多形红斑样损害,水疱几乎只发生于红斑或风团的基础上.血沉均增快,抗ANA、     

大疱性系统性红斑狼疮3例及文献复习

报告3例大疱性系统性红斑狼疮(BsLE).3例患者均为女性,年龄分别为36、57和23岁.临床上均表现为全身泛发水疱、大疱.皮损组织病理检查显示为表皮下水疱,真皮乳头层较多中性粒细胞浸润,2例出现基底细胞液化变性.直接免疫荧光检查:2例示免疫球蛋白G(IgG)和(或)免疫球蛋白A(IgA)、免疫球蛋白M(IgM)抗体线状沉积于基膜带(BMZ),1例IgA线状沉积于BMZ,无lgG、IgM沉积.3例均符合SLE的诊断标准.糖皮质激素和氨苯砜可有效控制水疱、大疱的发生.单独以IgA介导的BSLE在临床上罕见.     

病情与外周血嗜酸粒细胞计数平行的大疱性类天疱疮一例

报告1例病情与外周血嗜酸粒细胞计数相平行的大疱性类天疱疮.患者男,65岁.全身泛发红斑、水疱1个月,加重15天.皮肤科检查:皮损泛发头面颈、躯干、四肢及会阴部,基本损害为正常皮肤或红斑基础上出现大小不等的水疱,疱液为草黄色,散在红色糜烂面,尼氏征阴性,部分皮损表面敷以灰褐色痂片,以胸背部、四肢尤为严重.组织病理、直接免疫荧光、间接免疫荧光及盐裂皮肤直接免疫荧光检查结果符合大疱性类天疱疮.入院后依据病情变化,先后给予3次糖皮质激素冲击治疗,治疗过程中,定期监测血常规,提示外周血嗜酸粒细胞计数随病情波动.     

大疱性肥大细胞增生症

报告1例以头皮大疱为主要特点的大疱性肥大细胞增生症.患儿女,11个月.头皮反复起水疱、大疱3个月,每次发作前,面部潮红,头部出现风团样皮损,而后出现水疱、大疱,皮肤划痕征阳性.皮损组织病理和Giemsa染色证实为大疱性肥大细胞增生症.     

具有水疱大疱性皮损的簟样肉芽肿

蕈样肉芽肿伴有水疱大疱性皮损十分罕见.本文报告一例女性,51岁.因泛发性、瘙痒性红斑4个月而就诊。第一次皮肤活检提示为副银屑病。一年后,     

伴发血疱的泛发性硬化性萎缩性苔藓1例

患者女，64岁，四肢，躯干泛发性羊皮纸样萎缩性斑片5年，双乳内下方和剑突处起血疱1个月，组织病理检查：非血疱处皮损符合典型的硬化性萎缩性苔藓的病理改变，血疱处皮损示表皮下大疱形成，疱液中有大量的红细胞。     

结节性类天疱疮1例

结节性类天疱疮是大疱性类天疱疮的一种特殊类型,皮损多表现为泛发的角化过度的结节或斑块,有时结节的顶部可见小的水疱,好发于四肢伸侧,临床类似结节性痒疹.本病临床相对少见,笔者诊治1 例,现报告如下.     

特纳综合征合并大疱性类天疱疮1例

患者女,35岁,全身泛发红斑水疱8 d。皮肤科情况：全身泛发红斑,其上可见大小不等的水疱,部分水疱基底不红,为正常肤色,外阴及四肢部分水疱破溃渗出,水疱疱壁较厚,尼氏征(-),双下肢轻度肿胀。皮损组织病理及直接免疫荧光符合大疱性类天疱疮。患者30年前于外院确诊为特纳综合征。诊断：特纳综合征合并大疱性类天疱疮。给予糖皮质激素等常规治疗后效果不佳,加用静脉注射人免疫球蛋白治疗2周后病情好转。     

Epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune subepidermal bullous disease with clinical features similar to the genetic form of dystrophic epidermolysis bullosa. EBA is characterized by the presence of autoantibodies against type VII collagen which is a major component of the anchoring fibrils at the dermal‐epidermal junction. EBA can be divided into two main clinical types; mechanobullous and inflammatory EBA. Mechanobullous EBA, referred to as classic EBA, presents with skin fragility, blisters and dystrophic changes on trauma‐prone areas. Inflammatory EBA resembles other autoimmune subepidermal bullous diseases. Compelling evidence from mouse models supports a pathogenic role of autoantibodies against type VII collagen in EBA. Treatment of EBA is often unsatisfactory. The most widely used systemic treatment is corticosteroids. Colchicine and dapsone have been reported to be good treatment modalities when combined with corticosteroids. Some intractable cases of EBA have successfully been treated with intravenous immunoglobulin or rituximab.     

Coexistence of acquired hemophilia A and epidermolysis bullosa acquisita: Two case reports and published work review

Epidermolysis bullosa acquisita (EBA) is a rare chronic subepidermal bullous autoimmune disease. The occurrence of acquired hemophilia A (AHA) is low and so the coexistence of EBA and AHA is extremely rare. We herein described a case of EBA coexisting with AHA and a case of EBA coexisting with AHA and hepatitis B. These EBA may be related to the pathogenesis of AHA. In this study, we analyzed the clinical features in the two Chinese cases of EBA coexisting with AHA, and found esophageal hemorrhage and hematemesis were the main symptoms of both patients. Cyclosporin, prednisone and lamivudine effectively control EBA with AHA and hepatitis B. The dose of cyclosporin should be more than 4 mg/kg per day and the period of treatment should be longer than 5 months to reduce the risk of EBA co‐occurring with AHA.     

Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients

Epidermolysis bullosa acquisita (EBA) is an autoimmune sub-epidermal blistering disease characterized by autoantibodies to type VII (anchoring fibril) collagen. To date, however, direct evidence for a pathogenic role of human EBA autoantibodies has not been demonstrated. In this study, we affinity-purified anti-type VII collagen antibodies from EBA patients' sera and then injected them into adult hairless immunocompetent mice. Mice injected with EBA autoantibodies developed skin fragility, blisters, erosions, and nail loss on their paws - all features of EBA patients. By clinical, histological, immunological, and ultrastructural parameters, the induced lesions were reminiscent of human EBA. Histology showed bullous lesions with an epidermal-dermal separation. IgG and C3 deposits were observed at the epidermal-dermal junction. All mice had serum antibodies that labeled the dermal side of salt-split human skin like EBA sera. Direct immunogold electron microscopy specifically localized deposits of human IgG to anchoring fibrils. (Fab')(2) fragments generated from EBA autoantibodies did not induce disease. We conclude that EBA human patient autoantibodies cause sub-epidermal blisters and induce EBA skin lesions in mice. These passive transfer studies demonstrate that human EBA autoantibodies are pathogenic. This novel EBA mouse model can be used to further investigate EBA autoimmunity and to develop possible therapies.     

Administration of IgG fraction of epidermolysis bullosa acquisita (EBA) serum into mice

In order to study the pathogenic role of autoantibodies in the serum of EBA patients, we tried to induce EBA lesions in mice by administration of the IgG fraction of EBA serum via the intraperitoneal (i.p.) or subcutaneous (s.c.) routes into neonatal or adult mice. We also tried to induce EBA lesions in fetuses by intravenous (i.v.) injection of EBA serum into pregnant mice. This study demonstrates that IgG fraction of EBA serum injected into neonatal or adult mice, but not into fetal mice, deposits at the epidermo-dermal junction in a linear fashion but fails to induce bullae. The role of EBA serum in the pathogenesis of EBA lesions is discussed.     

Heavy and light chain isotypes of immunoglobulin in epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a chronic acquired blistering disease with characteristic clinical, pathologic, and immunopathologic features. The disease is characterized immunopathologically by circulating and tissue-bound IgG class autoantibodies (EBA antibodies) to the basement membrane zone of stratified squamous epithelium. Previous studies have shown that circulating and tissue-bound EBA antibodies are heterogenous in their ability to activate complement and have raised the possibility that functional heterogeneity might be related to IgG subclass restriction. In this study, we have characterized the IgG subclasses of the circulating and tissue-bound EBA antibodies by immunofluorescence and have examined the relationship between IgG subclass and complement binding. The results show that EBA antibodies belonging to all IgG subclasses are present in the skin of EBA patients. The results also show that EBA antibodies belonging to all IgG subclasses are present in the sera of most patients, including sera with and without complement binding EBA antibodies.     

Pathogenesis of epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering skin disease characterized by autoantibodies to type VII collagen. Clinically, a noninflammatory and an inflammatory variant of EBA can be distinguished. Despite major achievements in the understanding of EBA, current therapeutic options are far from optimal. However, with an emerging and more detailed understanding of the events ultimately leading to blister formation in EBA, novel therapeutic options may become available for patients with EBA. Therefore, this article reviews the current understanding of the pathogenesis of EBA and may indicate possible avenues towards a more targeted therapy for EBA and possibly other antibody-mediated autoimmune diseases.     

Epidermolysis bullosa acquisita with oesophageal stenosis

Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering disorder associated with autoimmunity to type VII collagen. Although the full clinical spectrum of EBA is still being defined, it is now known that EBA has greater clinical heterogeneity than previously suggested. We describe a patient with EBA which closely approximated the severity of the recessive form of dystrophic epidermolysis bullosa.     

Childhood epidermolysis bullosa acquisita during squaric acid dibutyl ester immunotherapy for alopecia areata

Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering disease associated with autoantibodies against type VII collagen. Although EBA manifests more frequently in adults, it can occur in childhood. We describe a 6‐year‐old boy who developed the inflammatory variant of EBA shortly after initiation of immunotherapy with squaric acid dibutyl ester (SADBE) for scalp alopecia areata. The disease rapidly regressed following SADBE discontinuation and starting combined steroid and dapsone therapy, and never recurred after treatment tapering and withdrawal. The association of EBA with other autoimmune diseases is common, but EBA occurring during alopecia areata has not been described previously. The development of EBA during SADBE treatment is also notable: the clinical history and therapeutic response in our patient point to a possible role of SADBE in EBA onset.     

Identification of quantitative trait loci in experimental epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. Several lines of evidence underscore the contribution of autoantibodies against type VII collagen (COL7) to the pathogenesis of EBA. Furthermore, EBA susceptibility is associated with the MHC haplotype in patients (HLA-DR2) and in immunization-induced EBA in mice (H2s). The latter study indicated an additional contribution of non-MHC genes to disease susceptibility. To identify non-MHC genes controlling EBA susceptibility, we intercrossed EBA-susceptible MRL/MpJ with EBA-resistant NZM2410/J and BXD2/TyJ as well as Cast mice. Mice of the fourth generation of this four-way autoimmune-prone advanced intercross line were immunized with a fragment of murine COL7 to induce EBA. Anti-COL7 autoantibodies were detected in 84% of mice, whereas deposition of complement at the dermal-epidermal junction (DEJ) was observed in 50% of the animals; 33% of immunized mice presented with overt clinical EBA. Onset of clinical disease was associated with several quantitative trait loci (QTLs) located on chromosomes 9, 12, 14, and 19, whereas maximum disease severity was linked to QTLs on chromosomes 1, 15, and 19. This more detailed insight into the pathogenesis of EBA may eventually lead to new treatment strategies for EBA and other autoantibody-mediated diseases.     

Black patients of African descent and HLA-DRB1*15:03 frequency overrepresented in epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disease (AIBD). However, higher EBA incidence and predisposing genetic factor(s) involving an HLA haplotype have been suspected in some populations. This retrospective study assessed the overrepresentation of black patients with EBA, its link with HLA-DRB1*15:03, and their clinical and immunological characteristics. Between 2005 and 2009, 7/13 (54%) EBA and 6/183 (3%) other-AIBD patients seen consecutively in our department were black (P=10(-6)); moreover 7/13 (54%) black patients and 6/183 (3%) white patients had EBA (P=10(-6)). In addition, between 1983 and 2005, 12 black patients had EBA. Finally, among the 19 black EBA patients, most of them had very atypical clinical presentations, 9 were natives of sub-Saharan Africa, 1 from Reunion Island, 7 from the West Indies, and 2 were of mixed ancestry. HLA-DRB1*15:03 allelic frequencies were 50% for African patients, significantly higher than the control population (P<10(-3)), and 21% for the West Indians (nonsignificant). High EBA frequencies have already been reported in American blacks significantly associated with the HLA-DR2. In conclusion, black-skinned patients developing EBA seem to have a genetic predisposition, and EBA should be suspected systematically for every AIBD seen in this population.