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。     

疱疹样皮炎中Th2样细胞因子活性

疱疹样皮炎(DH)是一种慢性表皮下水疱性疾病,特征是真皮乳头层和(或)沿基底膜有IgA颗粒状沉积,其血管周围有细胞浸润,主要由CD4~+T淋巴细胞和伴随不同数量的中性粒细胞和嗜酸粒细胞组成,这些细胞被认为在水     

疱疹样天疱疮1例

报告疱疹样天疱疮1例，患者女，因全身泛发斑疹、水疱伴瘙痒、糜烂9个月就疹，病理检查示表皮内棘层中部水疱，疱内含大量嗜中性粒细胞和嗜酸性粒细胞，基底细胞液化变性，真皮浅层淋巴组织细胞、少许嗜酸性粒细胞浸润。免疫荧光：棘细胞间IgG、C3轻沉积。最后诊断为疱疹样天疱疮。     

眼周局限性大疱性类天疱疮一例

患者,女,12岁。眼周反复红斑、水疱4个月,伴瘙痒。皮损组织病理示：表皮下水疱,真皮浅层淋巴细胞、嗜酸粒细胞、中性粒细胞等炎性细胞浸润。直接免疫荧光（DIF）：表皮基底膜IgG、C3阳性线状沉积。ELISA检测：血清抗BP230抗体 2.6 U/mL,抗BP180抗体阴性。诊断：局限性大疱性类天疱疮。予以甲泼尼龙、氨苯砜、吗替麦考酚酯治疗,目前在随访中。     

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。     

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.     

成人线状IgA大疱性皮病1例

患者男,37岁。全身反复出现红斑、斑丘疹、水疱,伴剧痒1年半。病理检查示表皮下水疱。真皮内中性粒细胞及嗜酸性粒细胞浸润;直接免疫荧光示IgA呈线状沉积于基底膜带。皮疹特点和组织病理类似疱疹样皮炎,后根据直接免疫荧光确诊为成人线状IgA大疱性皮病,给予环磷酰胺、糖皮质激素联合治疗,取得良好效果。     

疱疹样天疱疮1例

患者，男，71岁。主诉：全身红斑水疱伴瘙痒2年，反复发作。现病史：患者2年前开始躯干、四肢陆续出现散在红斑、水疱，疱易破溃呈糜烂或结痂，瘙痒剧烈。中药治疗效果不佳，皮疹逐渐增多，来我科就诊。经病理检查诊断为红斑型天疱疮，给予强的松60mg qd，雷公藤多甙20mg tid口服，皮疹消退后强的松开始减量。减量期间皮损曾多次反复，近几次复发时躯干、四肢出现多数环形红斑，边缘有密集排列的小水疱，取腹部小水疱做病理检查示：棘层中部水疱，疱内可见多数中性和少量嗜酸粒细胞浸润，真皮浅中层血管周围有淋巴细胞、组织细胞及嗜酸粒细胞浸润（图1）。直接免疫荧光检查（DIF）未发现表皮细胞问IgG、IgA、     

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。     

疱疹样天疱疮3例并文献复习

报道疱疹样天疱疮3例,其中男2例,女1例,平均年龄67岁;主要表现为全身皮肤红斑、水疱。组织病理检查示表皮内水疱,真皮浅中层嗜酸粒细胞浸润,直接免疫荧光表皮细胞间IgG沉积。 1例患者接受了间接免疫荧光检查,抗天疱疮抗体滴度为1:80,氨苯砜和糖皮质激素治疗有效。     

Cutaneous IgA deposits in bullous diseases function as ligands to mediate adherence of activated neutrophils

Linear IgA bullous dermatosis and dermatitis herpetiformis are inflammatory subepidermal blistering diseases characterized by IgA deposits at the cutaneous epithelial basement membrane and in dermal papillae, respectively. Inflammation in both disorders localizes to sites of IgA deposition and is characterized by a predominance of neutrophils. From these observations we postulate that IgA deposits in both diseases may contribute to the recruitment and/or localization of neutrophils. In this study we examined the ability of in vitro and in vivo bound IgA anti-basement membrane autoantibodies from patients with linear IgA bullous dermatosis and in vivo bound IgA deposits in dermal papillae from patients with dermatitis herpetiformis to mediate adherence of neutrophils stimulated by granulocyte macrophage colony-stimulating factor. The study showed that stimulated neutrophils adhered to basement membranes and dermal papillae containing IgA deposits. Adherence was IgA anti-basement membrane antibody concentration dependent and correlated with the immunofluorescence staining intensity of IgA deposits in dermal papillae. Adherence to IgA deposits but not IgG deposits could be inhibited by purified exogenous secretory IgA but not IgG and adherence to IgG deposits could be inhibited by purified exogenous IgG but not secretory IgA. These results provide direct experimental evidence that cutaneous IgA deposits in linear IgA bullous dermatosis and dermatitis herpetiformis can function as ligands for neutrophil adherence and have a role in the localization of inflammation in these disorders.     

A case of linear IgA disease in a child with IgA and IgG circulating antibodies directed to BPAg2

A 7-year-old Caucasian girl had multiple bullae on the trunk, upper and lower limbs (Fig. 1a,b) for 10 days. The lesions were large, tense, and asymptomatic, and mucosae were not involved. Laboratory findings were all normal. Histopathology revealed a subepidermal blister containing numerous neutrophils, eosinophils, and fibrin. Direct immunofluorescence of perilesional skin disclosed linear deposition of IgA and slight linear deposits of IgM at the basement membrane zone (Fig. 2). Indirect immunofluorescence on monkey esophagus and on human salt-split skin was negative. Immunoblot assay (IB), performed with an epidermal extract, revealed IgA and IgG antibodies directed to BPAg2 antigen (Fig. 3), while it was negative when performed on dermal extract. Enzyme-linked immunosorbent serologic assay using a commercial kit (MBL, Naka-Ku Nagoya, Japan) with the noncollagenous domain (NC16A) of the BPAg2 antigen was negative for both IgA and IgG. A diagnosis of linear IgA disease (LAD) was made and a treatment with dapsone (50 mg/day) and prednisolone (30 mg/day) was initiated. One month later, lesions had cleared.     

Vesicular pemphigoid

A patient with a pruritic vesicular eruption closely resembling dermatitis herpetiformis is described. Histopathologic examination of a biopsy specimen showed a subepidermal blister containing abundant eosinophils and neutrophils, whereas results of direct immunofluorescence studies demonstrated linear and homogeneous deposition of IgG and C3 along the basement membrane zone. Prednisone therapy was necessary to control the clinical symptoms. Similar cases have been described as "vesicular pemphigoid."     

Case of superficial mucocele of the lower lip

Superficial mucocele is a relatively rare bullous disease that develops in the oral mucosa. Although the number of reported cases is limited, it seems that the superficial mucocele has been recognized as an independent disease belonging to a single entity. We report a 48-year-old woman who repeatedly developed superficial mucocele in the oral mucosa. When she was admitted to our hospital she had a tense vesicle on her lower lip. A skin biopsy was taken from the vesicle. A blister containing neutrophils and erythrocytes was present in the mucous epithelium. There was a dermal infiltrate comprising neutrophils, mononuclear lymphocytic cells and eosinophils. Dilated salivary gland excretory ducts were seen in the lamina propria mucosae. Eosinophilic and amorphous materials, which were periodic acid-Schiff positive after digestion with diastase, and alcian blue positive, were deposited in the blister. Direct immunofluorescence was negative for immunoglobulin (Ig)G, IgM, IgA, C1q, C3 and C4. These histological findings led us to make a diagnosis of superficial mucoceles.     

Linear IgA disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD285 and a dermal 180-kDa protein

BACKGROUND: Linear IgA disease (LAD) of adults and children is mediated by IgA antibodies that target proteins of the epithelial adhesion complex. Most studies have concentrated on the epidermal-associated antigens; the dermal antigens remain unresolved. OBJECTIVES: To determine the dermal antigen repertoire of IgA and IgG antibodies in LAD. METHODS: Immunoblotting was carried out on salt-split and urea-extracted dermal skin extracts with IgA antibodies (63 adult and 34 childhood sera) and with IgG antibodies (49 adult and 18 childhood sera). RESULTS: Antigens were identified by IgA (61%), IgG (27%) and by both antibody isotypes (19%). LAD285 and an antigen of 180 kDa were the major dermal antigens identified, and antigens of 230 kDa, collagen VII and a protein under 100 kDa were identified less commonly. IgA autoantibodies from adults bound single antigens more frequently than multiple antigens; from children they bound single and multiple antigens equally. The binding of multiple antigens was, however, more common in children than adults. The IgG response was weaker. The 180-kDa antigen was the main IgG dermal target, and with a single exception, IgG autoantibodies targeted single antigens. CONCLUSIONS: There was an IgA and IgG response to dermal antigens in LAD; however, the dual antibody response was limited. The antibody response to LAD285 and a 180-kDa antigen (probably BP180) suggests that intermolecular epitope spreading of the antigens associated with the extracellular matrix/dermal components of the basement membrane contributes to the immunopathology of the disease. The restricted IgG response suggests that dermal-binding IgG autoantibodies are not pathologically significant.     

Dermatitis herpetiformis and vitiligo: report of a case and review of the literature

We describe the case of a 53-year-old woman presenting papulous and papulovesicular lesions that were highly pruritic, localized mostly in the achromic areas of vitiligo and symmetrically distributed on the elbows, the buttocks, the shoulders and the neck. The histopathological examination performed on the elbow's lesional skin showed the presence of neutrophils and fibrin microabscesses at the tips of dermal papillae, with a few eosinophils, and small separations between the dermis and epidermis just over the infiltrate. The overlying epidermis was uninjured. The performed tests detected IgA anti-endomysium, anti-thyrogloblin, anti-smooth muscle and anti-microsomal fraction autoantibodies; DIF showed the presence of IgA granular deposits at the dermo-epidermal junction, prevalently at the tips of dermal papillae. This is the tenth case reported of an association between dermatitis herpetiformis and vitiligo. Although the two disorders both have immunological pathogeneses, we think that the topographic coexistence of both disorders is coincidental.     

Linear IgA Bullous Dermatosis with Circulating IgG Autoantibodies to the 230 kD Epidermal Antigen

The patient was a 54-year-old woman with wide-spread bullous lesions on her trunk and oral mucosa. Histologic examination revealed a subepidermal blister with infiltration of neutrophils and eosinophils. Direct immunofluorescence showed an exclusively IgA deposition at the basement membrane zone (BMZ). Indirect immunofluorescence showed that the blister fluid, but not the serum, contained IgG antibodies against the BMZ antigen on the epidermal side of salt-split skin. Using immunoblot analysis with normal human epidermal extracts, both serum and blister fluid reacted with the 230 kD epidermal antigen. Using colloidal gold and direct immunoelectron microscopy, IgA deposition was detected in the lamina lucida. Clinically, the skin lesions responded well to dapsone. We diagnosed this case as linear IgA bullous dermatosis (LABD) with IgG class circulating autoantibodies against the epidermal 230 kD antigen. These antibodies were considered to be secondary to the damage to the epidermal basal keratinocyte in this case.     

Coexistence of psoriasis and an unusual IgG-mediated subepidermal bullous dermatosis: identification of a novel 200-kDa lower lamina lucida target antigen

Summary Bullous pemphigoid (BP) is characterized by autoantibodies against 230- and 180-kDa hemidesmosomal antigens located in the most superficial layers of the basement membrane zone (BMZ). Histologically. there is a predominance of eosinophils in the infiltrate. In a psoriatic patient, we identified an unusual autoimmune subepidermal bullous eruption which clinically resembled BP, but which was characterized by IgG autoantibodies against a novel 200-kDa lower lamina lucida component, Histologically there was a predominance of neutrophils in the infiltrate.
Direct immunofluorescence showed linear immunoglobulin (Ig)G and C3 deposition at the BMZ. The patient's IgG autoantibodies bound exclusively to the dermal side of salt-split normal human skin. Indirect immunogold electron microscopy showed a marked deposition of IgG at the lower lamina lucida and minimal deposition at the hemidesmosomes. Immunoblot analysis identified a unique 200-kDa autoantigen in dermal extracts and a faint band of the 230-kDa BP antigen in epidermal extracts. The patient responded dramatically well to cyclosporin A.
Although the patient's serum also reacted slightly with the 230-kDa BP antigen, there were significant findings different from the usual immunopathological changes of BP. These included finding a novel 200-kDa lower lamina lucida target antigen, the binding of IgG autoantibodies exclusively to the dermal side of the split skin and a predominance of neutrophils in blister infiltrate. The IgG autoantibodies against the 200-kDa lamina lucida target antigen seemed to play a major role in the pathogenesis of this unique autoimmune subepidermal dermatosis.     

The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.     

特应性皮炎患者皮损超微结构及免疫病理研究

目的:研究特应性皮炎(AD)患者皮损超微病理及免疫病理的表现,探讨AD的发病机制。方法:取21例患者外周血,测定血清IgE、IgA、IgG、IgM,并取典型皮损分别做超微组织病理和免疫病理检查。结果:16例AD患者血清IgE值>150IU/L,5例≤150IU/L,血清IgG、IgM值明显升高,而IgA值明显降低。电镜检查表皮可见激活的淋巴细胞,少数中性粒细胞侵入表皮,早期真皮可见胶原间质水肿,后期间质纤维呈波浪性增生,无论在表皮或真皮均可见到活化型的免疫应答细胞。结论:AD发病与免疫有关。治疗AD的靶细胞是肥大细胞。IgG1蛋白沉积可能与AD慢性感染有关。