盐裂皮损围围皮肤直接免疫荧光检查诊断表皮下水疱病

本文报告了应用盐裂皮损周围皮肤直接免疫荧光检查（ＤＩＦ）诊断２２例表皮下水疱病的结果，所有２２例表皮下水疱病盐裂皮损周围皮肤ＤＩＦ均显示ＩｇＧ免疫复合物沉积在表皮侧、真皮侧或表皮真皮两侧，阳性率为１００％。其中表皮侧１７例、表皮真皮两侧均有２例，此１９例均为大疱性类天疱疮（Ｂｐ）；真皮侧３例，２例为获得性大疱性在皮松解症（ＥＢＡ）、１例为大疱性系统性红斑狼疮（ＢＳＬＥ）。３例天疱疮和４例正常人皮肤均阴性。此法简便，易行，准确可靠，重复性好，值得推广使用。     

盐裂皮损围围皮肤直接免疫荧光检查诊断表皮下水泡病

本文报告了应用盐裂皮损周围皮肤直接免疫荧光检查（ＤＩＦ），诊断２２例表皮下水疱病的结果，所有２２例表皮下水泡病盐裂皮损周围皮肤ＤＩＦ均显示ＩｇＧ免疫复事物沉淀在表皮侧，真皮侧或表皮真皮两侧，阳性率为１００％，其中表皮侧１７例，表皮真皮两侧均有２例，此１９例的均为大泡性类天疱疮（Ｂｐ），真皮侧３例，２例为获得性大疱性表皮性松解症（ＥＢＡ），１例大疱性系统性红斑狼疮（ＢＳＬＥ），３例天疱疹和４例正常人     

盐裂解皮损周围皮肤直接免疫荧光鉴别诊断表皮下水疱病

应用盐裂皮损周围皮肤直接免疫荧光检查２２例表皮下水疱病的结果：ＩｇＧ免疫复合物沉积在表皮侧１７例，表皮真皮两侧均有２例，均为在性类天疱疮，真皮仙３例，２例为获得性大疱性表皮松解症，１例为大疱性系统红斑狼疮，对照组均阴性。此法简易易行，经济实用，准确可靠，值得推广使用。     

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     

儿童获得性大疱表皮松解症(附4例报道)

儿童获得性大疱表皮松解症（ＥＢＡ）是一种自身免疫性表皮下大疱病,比较少见。本文报道４例儿童ＥＢＡ,年龄为１、４、７、１４岁,均为男性。临床上似营养不良性大疱表皮松解症２例,儿童型线形ＩｇＡ大疱病２例。３例有口腔损害,伴血疱,萎缩性瘢痕和栗丘疹。病理为表皮下水疱。ＤＩＦ均示ＩｇＧ和Ｃ３呈线状分布于基底膜带,３例还见ＩｇＡ,１例见ＩｇＭ沉积于基底膜带。盐裂ＤＩＦ示３例ＩｇＧ沉积于真皮侧。ＩＩＦ示３例Ｉ     

NaCl分离皮肤为底物的IIF法鉴别诊断表皮下大疱病

对1989~1991年间,在本所就诊的100例表皮下大疱病,通过临床、组织病理、直接免疫荧光(DIF)、间接免疫荧光(IIF)法以及1M NaCl分离皮肤为底物的IIF法进行了诊断和评价.结果发现DIF检查的100例中有76例皮肤BMZ有免疫反应物沉积,另24例为阴性,但有典型的自身免疫性大疱病的临床表现;根据临床、DIF和分离皮IIF法修正诊断出大疱性类天疱疮(BP)54例、获得性大疱性表皮松解症(EBA)8例、线状IgA大疱性皮病(LABD)7例(成人4、儿童3),瘢痕性类天疱疮(CP)7例、水疱性红斑狼疮(BSLE)3例、迟发性皮肤卟啉症(PCT)2例、BP和寻常型天疱疮(PV)并发1例,BP和疱疹样皮炎(DH)并发1例,有17例未定.研究结果发现分离皮IIF法对提高表皮下大疱病的诊断水平有较重要的应用价值.但由于CP的抗BMZ抗体可分别出现在表皮侧或真皮侧,所以分离皮IIF法不能单独鉴别CP和BP、CP和EBA.应该结合临床、免疫印迹和免疫电镜等方法进一步诊断,从而也表明分离皮IIF法有一定的局限性.     

大疱性扁平苔藓和类天疱疮性扁平苔藓的临床和病理比较

大疱性扁平苔藓(BLP)和类天疱疮性扁平苔藓(LPP)是两个独立的疾病。前者为小疱, 而后者的扁平苔藓(LP)常呈急性和泛发性,在受累和未受累的皮肤上突发大疱,免疫荧光(IF)类似大疱性类天疱疮(BP)。作者共观察了4例(例1、2为 LPP,例3、4为 BLP)患者,均为女性,平均年龄44.5岁。例1、2为肢体、躯干、粘膜部位广泛性 LP 伴瘙痒,以后在 LP 的斑块、红斑和正常皮肤上出现大疱。组织病理示表皮下大疱,真皮及血管周围有淋巴细胞、嗜酸细胞、部分中性白细胞浸润。DIF 显示基底膜带 C3呈线状沉积,IIF 阴性。均以口服皮质类固醇(60mg/d)治疗。例1在6个月后皮损消退,例2加服硫唑嘌呤150mg/d,2年后仍有皮疹,减药后有新发     

糖尿病性大疱病

1963年Rocca等首次报告了14例糖尿病患者在双足发生非外伤性大疱损害.大疱位置浅表,无自觉症状,缓慢愈合后不留下瘢痕.1967年Cantwell等称之为糖尿病性大疱病(Bullosis diabeticorum).并发现这些大疱均具有多发性、无症状和位于表皮内的特点.此后,各家均有类似报道.但1975年Kerl则发现此种大疱位于表皮下,在真皮内没有或仅有轻度的炎性浸润.本文在200例糖尿病患者中,发现2例有大疱性损害,其发生率为1%.     

盐裂间接免疫荧光技术在大疱性类天疱疮鉴别诊断中的应用研究

目的:探讨盐裂皮肤间接免疫荧光(IIF)技术在大疱性类天疱疮(BP)鉴别诊断中的作用.方法:应用盐裂IIF技术检测78例常规方法诊断为BP的患者血清.结果:43例血清IgG沉积于表皮侧,7例IgG沉积于双侧,11例IgG沉积于真皮侧,另有17例双侧均未见抗体沉积.结论:盐裂IIF仅能用于BP的初步鉴别诊断.     

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.     

Two cases of subepidermal blistering disease with anti-p200 or 180-kD bullous pemphigoid antigen associated with psoriasis

We describe two patients with psoriasis vulgaris who subsequently developed a subepidermal blistering disease which disclosed IgG and C3 at the basement membrane zone in direct immunofluorescence. The first case was a 75-year-old Japanese man with herpetiform lesions. Histopathology showed neutrophil infiltration. IgG antibodies bound to the dermal side of the salt-split skin. Immunoblot analysis identified a 200-kD antigen in dermal extracts. The second case was a 70-year-old Japanese man. Histopathology showed eosinophil infiltration. IgG antibodies bound to the epidermal side of salt-split skin. Immunoblot analysis identified a 180-kD bullous pemphigoid (BP) antigen in epidermal extracts. We review the clinical and pathological features of psoriatic patients who presented a subepidermal blistering disease in which antigens were detected by immunoblot analysis; i.e., anti-p200 pemphigoid (14 cases) or BP (12 cases). There were few distinct clinical differences between two diseases. However, neutrophils were predominant in anti-p200 pemphigoid, while eosinophils were predominant in BP. After blister formation, ciclosporin was used effectively in addition to systemic steroids in the treatment of anti-p200 pemphigoid. On the other hand, ciclosporin was not used in the treatment of BP with psoriasis.     

表皮下大疱病的鉴别诊断和抗原表达区域性差别的研究

通过间接免疫荧光和盐裂皮损周围皮肤直接免疫荧光（简称盐裂ＤＩＦ），分别研究正常人皮肤、类天疱疮（ＢＰ）及获得性大疱性表皮松解症（ＥＢＡ）抗原表达的区域性差别和表皮下大疱病鉴别诊断。 窝、肘窝、上背、下背、股内侧和下腹部皮肤ＢＰ抗原表达率较高；膝、阳窝、足背、肘、肘窝和下腹部皮肤ＥＢＡ抗原表达率较高。皮肤ＤＩＦ显示２５例表皮下大疱病中１６例（６４％）基底膜带有Ｃ３或ＩｇＧ或伴Ｃ３和ＩｇＡ沉积；盐裂ＤＩＦ表明２５例（１００％）均有ＩｇＧ或伴Ｃ３和ＩｇＡ沉积在表皮侧或真皮侧。结果提示，ＢＰ抗原高表达率与皮损好发部位相一致；ＥＢＡ抗原高表达率一部分与皮损好发部位一致。盐裂ＤＩＦ不仅提高ＤＩＦ阳性率，而且根据免疫反应物沉积部位可以鉴别出ＢＰ与ＥＢＡ以及大疱性系统性红斑狼疮。     

Immunoelectron microscopy in subepidermal autoimmune bullous diseases: a prospective study of IgG and C3 bound in vivo in 32 patients

Thirty-two patients suffering from subepidermal autoimmune bullous disease were studied prospectively by clinical examination and immunoelectron microscopy. Clinically, 1 patient had herpes gestationnis, 14 typical bullous pemphigoid (BP), 3 epidermolysis acquisita (EBA), 3 cicatricial pemphigoid (CP), and 11 patients overlapping clinical diseases. These 11 patients shared clinical features of BP, EBA, or CP and a clinical diagnosis could not be done safely. Immunoelectron microscopy revealed diaminobenzidine deposits in 20 patients on the epidermal side of dermo-epidermal junction in the lamina lucida as in BP. In 5 patients, deposits located mostly under the anchoring fibril zone, in the floor of a sublamina densa dermoepidermal separation for 2 of them, were consistent with a diagnosis of EBA. In 6 patients, deposits were located mostly in the lamina densa, in the floor of a dermoepidermal separation occurring in the lamina lucida for 3 of them. This suggests that some of these 6 patients had neither EBA or BP, but another autoimmune bullous disease again, an uncharacterized component of dermoepidermal junction located in the lamina densa. Finally, a correlation exists between the sites of IgG and/or C3 components on epidermal or dermal side of dermoepidermal junction and the presence or absence of characteristic clinical features such as scar, milia formation, or mucosal involvement.     

Case of subepidermal autoimmune bullous disease with psoriasis vulgaris reacting to both BP180 C‐terminal domain and laminin gamma‐1

A number of cases of psoriasis vulgaris developing bullous skin lesions have been diagnosed as either bullous pemphigoid with antibodies to the 180‐kDa bullous pemphigoid antigen (BP180) non‐collagenous 16a (NC16a) domain or anti‐laminin‐γ1 (p200) pemphigoid. We report a case of subepidermal bullous disease with psoriasis vulgaris, showing antibodies to both BP180 C‐terminal domain and laminin‐γ1. A 64‐year‐old Japanese man with psoriasis vulgaris developed exudative erythemas and tense bullae on the whole body but he did not have mucosal involvement. The blistering lesion showed subepidermal blisters histopathologically. In indirect immunofluorescence of 1 mol/L NaCl‐split skin, immunoglobulin (Ig)G antibodies reacted with both the epidermal and dermal side. Immunoblotting showed positive IgG with recombinant protein of BP180 C‐terminal domain and 200‐kDa laminin‐γ1 in normal human dermal extract.     

Autoimmune subepidermal blistering diseases in Uganda: correlation of autoantibody class with age of patients

BACKGROUND: No data are available on the incidence and immunoreactivity of autoimmune subepidermal blistering skin diseases in East Africa. METHODS: All patients with frank blisters/erosions on the skin and/or mucous membranes that attended the Department of Dermatology at Mbarara University, Uganda, from May 2000 to June 2002, were investigated. The diagnosis was based on the clinical presentation and on the presence of circulating autoantibodies detected by indirect immunofluorescence microscopy on 1 m NaCl-split human skin and by Western blotting of recombinant and cell-derived forms of BP180, BP230, and type VII collagen. RESULTS: Twenty-two patients with autoimmune subepidermal blistering skin disorders were identified, including nine with bullous pemphigoid (41%), four with linear immunoglobulin A (IgA) disease (18%), three with mucous membrane pemphigoid (14%), two with linear IgG/IgA bullous dermatosis (9%), and one each with cicatricial pemphigoid and epidermolysis bullosa acquisita (5%). In addition, two patients with immunoreactivity to both the epidermal and dermal side of salt-split skin by indirect immunofluorescence microscopy, who were unreactive to type VII collagen, were provisionally diagnosed as "mixed pemphigoid" (9%). In patients with subepidermal blistering diseases, IgG reactivity correlated significantly with old age, whereas younger patients preferentially developed IgA autoantibodies (P = 0.024). CONCLUSIONS: The age of patients with autoimmune subepidermal blistering diseases appears to influence the immunoglobulin class of autoantibodies. The high frequency of IgA autoantibodies in Ugandan patients may be explained by the age distribution of the Ugandan population.     

The localization of the bullous pemphigoid and cicatricial pemphigoid antigens: direct and indirect immunofluorescence of suction blisters

The location of in vivo bound immunoreactants was studied in 37 patients with subepidermal blistering diseases by direct immunofluorescence (IMF) on suction blisters taken from uninvolved forearm skin. The patients studied included 18 with bullous pemphigoid (BP), nine with cicatricial pemphigoid (CP), three with acquired epidermolysis bullosa (EBA) and 7 hybrid cases. The patterns of IMF in the suction blisters were: BP, epidermal 1, dermal 1, combined 4, negative 12; CP, epidermal 1, dermal 2, negative 6; EBA, dermal 2, negative 1; and 'hybrid' patients, epidermal 3, negative 4. The different patterns of suction blister staining could not be correlated with the clinical features of the patients in respect of mucous membrane involvement, scars or milia or a history of skin fragility. Both BP and CP are probably heterogeneous in respect of their antigen specificity, and the two diseases cannot reliably be distinguished by the patterns of direct IMF on suction blisters. In addition, some individual patients with BP have more than one target antigen as indicated by a combined pattern of suction blister fluorescence. The lack of correlation between the pattern of suction blister fluorescence and the clinical features suggests that factors other than antigen specificity determine the clinical expression of subepidermal blistering diseases.     

Subepidermal blistering disease with autoantibodies against a novel dermal 200-kDa antigen

A number of autoimmune subepidermal blistering diseases are characterized by the distinct autoantigens of the cutaneous basement membrane zone. Recently, a few cases with autoantibodies against a novel 200-kDa dermal protein have been reported. We collected nine cases of subepidermal blistering disease with IgG antibodies against this 200-kDa antigen. In this report, we describe the clinical and immunological appearances in these cases. Five cases showed bullous pemphigoid-like features, one case resembled dermatitis herpetiformis, and another case showed mixed features of bullous pemphigoid and linear IgA bullous dermatosis. It was interesting to note that psoriasis coexisted in four cases. By indirect immunofluorescence on 1 M NaCl split skin, IgG antibodies from all sera reacted with the dermal side of the split. By immunoblot analysis, IgG antibodies recognized a 200-kDa protein of dermal extract. IgG affinity-purified antibodies on the 200-kDa immunoblot membrane stained the dermal side of 1 M NaCl split skin. Various examinations suggested that the 200-kDa antigen is not identical to any chains of laminins-1, -5 or -6. This autoimmune subepidermal blistering disease against the dermal 200-kDa protein may form a new distinct entity, which often associates with psoriasis.     

盐裂皮肤直接和间接免疫荧光联合应用鉴别诊断表皮下大疱病的研究

本文探讨盐裂皮肤ＤＩＦ和盐裂皮肤ＩＩＦ联合应用鉴别诊断表皮下大疱病的价值。２０例两种盐裂皮肤免疫荧光均阳性的病例比较表明，盐裂皮肤ＩＩＦ示抗基底膜带抗体结合表皮侧或真皮侧与盐裂皮肤ＤＩＦ示免疫反应物（ＩｇＧ、ＩｇＡ、Ｃ＿３等）沉积于表皮例或真皮侧的部位基本一致。提示多数情况下盐裂皮肤ＤＩＦ或ＩＩＦ均可单独用于表皮下大疱病诊断，两者对比分析可以提高诊断率。     

A bullous skin disease patient with autoantibodies against separate epitopes in 1 mol/L sodium chloride split skin.

BACKGROUND--We describe a patient with a subepidermal bullous skin disease associated with autoantibodies recognizing separate epitopes in 1 mol/L sodium chloride (NaCl) split skin. OBSERVATIONS--Direct immunofluorescence microscopy showed deposits of immunoglobulins and C3 in a continuous pattern in the patient's epidermal basement membrane zone. Direct immunoelectron microscopy demonstrated thick deposits of IgG overlying the lamina lucida and the lamina densa in a unique pattern. The patient had circulating IgG anti-basement membrane zone antibodies that bound both sides of 1 mol/L NaCl split skin, exhibited at least a fourfold-higher titer against the dermal side of this test substrate, and bound basal keratinocyte hemidesmosomes as well as focal sites along the superior portion of the lamina densa on indirect immunoelectron microscopy. Affinity purification of anti-basement membrane zone antibodies against epidermal or dermal strips of 1 mol/L NaCl split skin yielded IgG that only bound the side of split skin from which it was eluted. The patient's serum contained IgG that immunoprecipitated and immunoblotted the 230- and 170-kd bullous pemphigoid antigens. Affinity purification of patient antibody against bullous pemphigoid antigen immobilized on nitrocellulose paper yielded IgG that bound only the epidermal side of 1 mol/L NaCl split skin. The patient showed no evidence of reactivity against type VII collagen by direct immunoelectron microscopy, indirect immunoelectron microscopy, or immunoblot. CONCLUSIONS--This patient's bullous skin disease is associated with IgG anti-basement membrane zone antibodies with two specificities: one recognizing the bullous pemphigoid antigen in the epidermal side of 1 mol/L NaCl split skin, and another binding a distinct, yet presently unidentified, epitope in the superior aspect of the lamina densa.     

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.