BACKGROUND & AIMS: :Esophageal involvement of pemphigus vulgaris (PV) had been considered an exceptional event. We present the case of a woman with PV who developed esophageal involvement while being treated with azathioprine and resolved after steroid therapy. This case highlights that esophageal involvement of PV might be resistant to immunosuppressive therapy other than steroids.

背景与目标： : 食管受累寻常天疱疮 (PV) 被认为是一个特殊事件。我们介绍了一名患有PV的妇女，该妇女在接受硫唑嘌呤治疗时出现食道受累，并在类固醇治疗后消退。该病例突出表明，PV的食道受累可能对类固醇以外的免疫抑制疗法具有抵抗力。

BACKGROUND & AIMS: :Adult-onset Still's disease is a systemic disorder without specific histological feature. Diagnosis requires to rule out any other disorder including neoplasia. Nevertheless, patients with paraneoplastic adult-onset Still's disease have been reported. We report a patient with an adult-onset Still's disease who presented with a liver involvement at onset. Two years later, a liver angiosarcoma was diagnosed. This report underlines the difficulty of the diagnosis of the adult-onset Still's disease even in the presence of Yamaguchi et al.'s [J Rheumatol 19 (1992) 424-30] and Fautrel et al.'s [Medicine 81 (2002) 194-200] classification criteria and may suggest a link between the initial clinical picture and the discovery nearly two years later, of a liver angiosarcoma.

背景与目标： : 成人型斯蒂氏病是一种全身性疾病，没有特定的组织学特征。诊断需要排除任何其他疾病，包括肿瘤。尽管如此，已经报道了患有副肿瘤性成人斯蒂里氏病的患者。我们报告了一名成人Still病患者，该患者在发病时表现为肝脏受累。两年后，诊断出肝脏血管肉瘤。该报告强调了即使在存在Yamaguchi等人的 [J风湿病19 (1992) 424-30] 和Fautrel等人的 [医学81 (2002) 194-200] 分类标准的情况下，成人发病的斯蒂尔病的诊断困难，并且可能建议最初的临床情况和近两年后的发现，肝脏血管肉瘤。

BACKGROUND & AIMS: A 54-year-old woman with clinically diagnosed paraneoplastic limbic encephalitis secondary to adenocarcinoma of the lung is described. Neuropsychological evaluation revealed intact visual perception, visual construction, language, speeded processing, and verbal abstract reasoning in the presence of a severe anterograde amnesia for both verbal and visual information. A profound consolidation problem is discussed in view of other diseases of the mesial temporal lobes resulting in impaired consolidation of new material.

背景与目标： 描述了一名54岁的女性，其临床诊断为继发于肺腺癌的副肿瘤性边缘性脑炎。神经心理学评估显示，在存在严重的顺行性遗忘的口头和视觉信息的情况下，完整的视觉感知，视觉构造，语言，快速处理和口头抽象推理。鉴于中颞叶的其他疾病导致新材料的巩固受损，讨论了一个深刻的巩固问题。

BACKGROUND & AIMS: This report describes a case of paraneoplastic neurological syndrome associating a subacute sensory neuronopathy and an intestinal pseudo-obstruction in a 64-year old man with a small cell lung cancer. Various paraneoplastic neurological syndromes have been described in association with small cell lung cancer. In our patient anti-Hu antibodies were identified by indirect immunohistochemistry and western-blot analysis. This antibody constitutes an informative tool in assessing the paraneoplastic origin of neurologic symptoms when the etiological inquiry is negative. Its positivity is important in promoting the search for an underlying malignancy and should lead to repeat investigations if the first investigations are normal.

背景与目标： 本报告描述了一例副肿瘤神经系统综合症，该病例与一名64岁的小细胞肺癌患者的亚急性感觉神经病和肠假性梗阻有关。已经描述了与小细胞肺癌相关的各种副肿瘤神经综合征。在我们的患者中，通过间接免疫组织化学和western印迹分析鉴定了抗Hu抗体。当病因询问为阴性时，该抗体构成了评估神经症状的副肿瘤起源的有用工具。它的阳性对于促进寻找潜在的恶性肿瘤很重要，如果首次调查正常，则应导致重复调查。

BACKGROUND & AIMS: :The onset and course of pemphigus are often the result of an interaction between predisposing genetic factors and environmental triggering agents. The latter are heterogeneous, numerous and increasing, ranging from drug intake (the commonest cause of pemphigus induction) to the exposure to physical agents (heat, UV and ionizing rays, surgical and cosmetic procedures), viral infections (especially by herpesvirus), contact dermatitis, certain diet ingredients and even emotional stress. Alerting physicians and pemphigus patients to the effects that unsuspected precipitating factors may have on the progression of the disease is an important task. In fact, avoiding or limiting deleterious habits (e.g. overindulging in unnecessary drugs) and suggesting alternative ways (e.g. substituting potentially pemphigus-inducing drugs with others considered harmless in this respect) may be a useful precaution in the management of pemphigus patients, since it can improve the efficacy of conventional treatments, reduce the risks of relapses and sometimes result in a cure.

背景与目标： : 天疱疮的发作和病程通常是易感遗传因素和环境触发因素之间相互作用的结果。后者是异质的，数量众多且不断增加，从药物摄入 (天疱疮诱导的最常见原因) 到暴露于物理试剂 (热，紫外线和电离射线，外科手术和美容手术)，病毒感染 (尤其是疱疹病毒)，接触性皮炎，某些饮食成分甚至情绪压力。提醒医师和天疱疮患者注意未怀疑的诱发因素可能对疾病进展的影响是一项重要任务。事实上，避免或限制有害习惯 (例如过度沉迷于不必要的药物) 和建议替代方法 (例如用在这方面被认为无害的其他可能诱发天疱疮的药物替代) 可能是治疗天疱疮患者的有用预防措施，由于它可以提高常规治疗的疗效，降低复发的风险，有时可以治愈。

BACKGROUND & AIMS: OBJECTIVE:To analyze the clinical feature, efficacy of treatment and prognosis in familial benign chronic pemphigus (FBCP). METHODS:Sixty-nine cases of FBCP were retrospectively analyzed. RESULTS:The ratio of male to female is 3.93:1 in 69 patients (55 males, 14 females). The mean age at the onset was 29.09 years (3-60 years). There was familial history in 27 families in all of the cases. The lesion usually involved in genital area, neck, axillae and popliteal fossa. Erythemas and vesicles on the soles were seen only in 1 case. Histopathologically 44 cases had special features of FBCP, and immunopathologically 8 cases were direct immunofluorescence (DIF) negative, in which one case had C3 linear deposition along dermoepidermal junction. The combined regimen was more effective. The low-dose X-ray could improve the effect. CONCLUSION:The disease is transmitted as an irregular autosomal dominant trait. The condition in males is more frequent than that in females, probably owing to the different level of female hormone in both sexes. Our patients have the same clinical features as those reported in the literature, but the erythema, vesicle lesions on sole have not been documented in the literature. The combined therapy should be adopted in this condition.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A not well-appreciated but clinically important aspect of malignant tumours is their effects on distantly located host cells. The effects, termed paraneoplastic syndromes, also pose an intriguing mechanistic problem: how do malignant cells influence properties of host cells not in contact with them? Erythrocytes from the circulation of rats bearing intraperitoneal Yoshida ascites sarcoma exhibit higher agglutinability with concanavalin A (Con A) than the cells from normal animals. Since the tumour and the red cells are not in contact, the enhanced agglutinability of the latter is a paraneoplastic effect. The mechanism by which the tumour brings about this effect is investigated as a model for paraneoplastic syndromes. The cell-free ascites fluid is able to impart high agglutinability on cells from normal animals in vitro. Also, when injected intraperitoneally in normal animals, the ascites fluid is able to enhance the agglutinability of erythrocytes in circulation. Apparently the tumour produces a substance(s) that appears in the ascites fluid and is able to diffuse into circulation, explaining the mechanism by which it can reach distant sites. From the cell-free ascites fluid three fractions have been isolated that are active in vitro. Of these, only one showed activity in vivo. From this fraction, a glycoprotein has been purified to homogeneity that confers maximal Con A-agglutinability on normal erythrocytes at 8 x 10(-7)M, at which concentration 6,400 molecules bind per cell. The protein has a molecular weight of 600 kDa in the native state and a pI of 5.35. It is made up of 4 identical subunits of Mr 170,000. It is detected in the plasma of tumour-bearing but not normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 恶性肿瘤的一个不被重视但临床上重要的方面是它们对遥远定位的宿主细胞的影响。这种效应被称为副肿瘤综合征，也带来了一个有趣的机制问题: 恶性细胞如何影响不与它们接触的宿主细胞的特性？腹膜内携带吉田腹水肉瘤的大鼠循环中的红细胞与刀豆球蛋白A (Con A) 相比，其凝集性高于正常动物的细胞。由于肿瘤和红细胞不接触，因此后者的凝集能力增强是一种副肿瘤作用。研究了肿瘤引起这种作用的机制，作为副肿瘤综合征的模型。无细胞腹水能够在体外对正常动物的细胞赋予高度凝集性。同样，当在正常动物中腹膜内注射时，腹水能够增强循环中红细胞的凝集能力。显然，肿瘤会产生一种物质，这种物质会出现在腹水中，并能够扩散到循环中，从而解释了它可以到达远处的机制。从无细胞的腹水液中分离出三个在体外具有活性的部分。其中，只有一个在体内显示出活性。从该级分中，糖蛋白已被纯化至同质，其在8 × 10(-7)M的正常红细胞上赋予最大的Con-凝集性，在该浓度下6,400分子结合每个细胞。该蛋白质在天然状态下具有600 kDa的分子量和5.35的pI。它由Mr 170,000的4个相同的亚基组成。它是在荷瘤大鼠的血浆中检测到的，但不是正常大鼠。(摘要截短于250字)

BACKGROUND & AIMS: :Desmoplakin I and II are important components of the attachment plaque of the desmosome which mediates cell to cell adhesion, in epithelial cells. In this study we used well-characterized antibody against desmoplakin I and II immunohistochemically and immunoelectron microscopically on two cases of pemphigus vulgaris and one case of pemphigus erythematosus and two cases each of Hailey-Hailey's disease and Darier's disease. In the normal human epidermis the desmosomes were demonstrated in a dotted pattern along cell periphery. In pemphigus vulgaris and pemphigus erythematosus acantholytic cells and the perilesional cells exhibited normal dotted pattern along the cell periphery. In Hailey-Hailey's disease and Darier's disease, the dotted pattern is lost in acantholysed and perilesional areas and anti-desmoplakin I + II positive proteins were observed diffusely in the cytoplasm. Immunoelectron microscopical findings correspond to these light microscopical observations. It is concluded that in autoimmune acantholytic disease such as pemphigus vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as Hailey-Hailey's disease and Darier's disease primary or secondary abnormalities abnormalities of desmosomes may be involved in their pathogenesis.

背景与目标： : Desmoplakin I和II是上皮细胞中介导细胞与细胞粘附的桥粒附着斑块的重要组成部分。在这项研究中，我们对2例寻常型天疱疮和1例红斑天疱疮以及2例Hailey-Hailey病和Darier病各2例进行了免疫组织化学和免疫电子显微镜下的抗desmoplakin I和II抗体。在正常人表皮中，桥粒沿细胞外围以虚线显示。在寻常型天疱疮和红斑天疱疮中，棘层分解细胞和周围细胞沿细胞外围显示出正常的点状模式。在Hailey-Hailey病和Darier病中，在棘突和周围区域失去了点状图案，并且在细胞质中广泛观察到抗desmoplakin I II阳性蛋白。免疫电子显微镜检查结果与这些光学显微镜观察结果相对应。结论在自身免疫性棘皮病如寻常型天疱疮和红斑天疱疮中，即使在棘层分解细胞中，结膜蛋白也是完整的，而在寻常型和红斑天疱疮等遗传性皮肤病中，结膜蛋白即使在棘层分解细胞中也是完整的，而在遗传皮肤病中，例如Hailey-Hailey病和Darier病，桥粒的原发性或继发性异常可能与其发病机理有关。

BACKGROUND & AIMS: :Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis produced as a consequence of desmoglein (Dsg) and non-Dsg autoantibodies binding to several targeting molecules localized on the membrane of keratinocytes. Nitric oxide (NO) may exert a pathogenic function in several immunological processes. We have previously demonstrated that neural nitric oxide synthase (nNOS) plays part in PV acantholysis. Also, our group has described a relevant role for HER [human epidermal growth factor receptor (EGFR) related] isoforms and several kinases such as Src (Rous sarcoma), mammalian target of rapamycin (mTOR) and focal adhesion kinase (FAK), as well as caspases in PV development. Using a passive transfer mouse model of PV, we aimed to investigate the relationship between the increase in nNOS and EGFR, Src, mTOR and FAK kinase upregulation observed in PV lesions. Our results revealed a new function for nNOS, which contributes to EGFR-mediated PV acantholysis through the upregulation of Src, mTOR and FAK. In addition, we found that nNOS participates actively in PV at least in part by increasing caspase-9 and caspase-3 activities. These findings underline the important issue that in PV acantholysis, caspase activation is a nNOS-linked process downstream of Src, mTOR and FAK kinase upregulation.

背景与目标： : 寻常型天疱疮 (PV) 是一种自身免疫性水疱性皮肤病，其特征是由于desmoglein (Dsg) 和非Dsg自身抗体结合到位于角质形成细胞膜上的几种靶向分子而产生的基底上棘皮溶解。一氧化氮 (NO) 可能在几个免疫过程中发挥致病功能。我们以前已经证明神经一氧化氮合酶 (nNOS) 在PV棘层分解中起作用。此外，我们的小组还描述了HER [人表皮生长因子受体 (EGFR) 相关] 亚型和几种激酶的相关作用，例如Src (Rous肉瘤)，雷帕霉素的哺乳动物靶标 (mTOR) 和粘着斑激酶 (FAK)，以及PV开发中的caspase。使用PV的被动转移小鼠模型，我们旨在研究在PV病变中观察到的nNOS增加与EGFR，Src，mTOR和FAK激酶上调之间的关系。我们的结果揭示了nNOS的新功能，它通过Src，mTOR和FAK的上调促进了EGFR介导的PV棘皮分解。此外，我们发现nNOS至少部分通过增加caspase-9和caspase-3活动来积极参与PV。这些发现强调了一个重要问题，即在PV棘层分解中，caspase激活是Src，mTOR和FAK激酶上调下游的nNOS连接过程。

BACKGROUND & AIMS: :We present a 27-yr-old female with gonadal dysgenesis (46, XY), who presented to our hospital with poor consciousness, aphasia, restlessness, and visual hallucination. Physical examination revealed normal breast development and normal external female genetalia. Computed tomography scan of the head and neck revealed the presence of brain edema, hydrocephalous, and a localized hypodense lesion in the hypothalamus. Her serum was positive for the anti-Ma2, which is associated with paraneoplastic encephalitis syndrome. Computed tomography of the abdomen revealed the presence of a 7.5×5.3×3.0 cm solid pelvic mass. Interestingly, a single microscopic focus of dysgerminoma was identified in a background of stromal fibrosis and focal dystrophic calcifications. No ovarian stroma or testicular tissue was identified. To our knowledge, this is the first case of gonadal dysgenesis presenting with anti-Ma2 paraneoplastic encephalitis with dysgerminoma. A discussion about paraneoplastic encephalitis with a microscopic dysgerminoma associated with anti-Ma2 antibody is presented.

背景与目标： : 我们介绍了一名患有性腺发育不全的27岁女性 (46，XY)，她因意识不良，失语，躁动和视觉幻觉而到我们医院就诊。体格检查显示乳房发育正常，外部女性生殖器正常。头部和颈部的计算机断层扫描显示存在脑水肿，脑积水和下丘脑局部低密度病变。她的血清对anti-Ma2呈阳性，这与副肿瘤性脑炎综合征有关。腹部计算机断层扫描显示存在7.5 × 5.3 × 3.0厘米实性骨盆肿块。有趣的是，在基质纤维化和局灶性营养不良钙化的背景下，发现了无性细胞瘤的单个微观焦点。未发现卵巢基质或睾丸组织。据我们所知，这是第一例出现anti-Ma2副肿瘤性脑炎伴无性细胞瘤的性腺发育不全。提出了关于副肿瘤性脑炎与anti-Ma2抗体相关的微观无性细胞瘤的讨论。

BACKGROUND & AIMS: :Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease characterized by detachment of keratinocytes (acantholysis). It has been proposed that PV IgG might trigger signaling and that this process may lead to acantholysis. Indeed, we recently identified a rapid and dose-dependent phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and heat shock protein (HSP) 27 after binding of PV antibodies to cultured keratinocytes. In human keratinocyte cultures, inhibitors of p38MAPK prevented PV IgG-induced phosphorylation of HSP27 and, more importantly, prevented the early cytoskeletal changes associated with loss of cell-cell adhesion. This study was undertaken to (i) determine whether p38MAPK and HSP25, the murine HSP27 homolog, were similarly phosphorylated in an in vivo model of PV and (ii) investigate the potential therapeutic use of p38MAPK inhibition to block blister formation in an animal model of PV. We now report that p38MAPK inhibitors prevented PV blistering disease in vivo. Targeting the end-organ by inhibiting keratinocyte desmosome signaling may be effective for treating desmosome autoimmune blistering disorders.

背景与目标： : 寻常型天疱疮 (PV) 是一种威胁生命的自身免疫性水疱性皮肤病，其特征是角质形成细胞脱离 (棘皮松解)。已经提出PV IgG可能触发信号传导，并且该过程可能导致棘层分解。实际上，我们最近确定了PV抗体与培养的角质形成细胞结合后，p38丝裂原活化蛋白激酶 (p38MAPK) 和热休克蛋白 (HSP) 27的快速且剂量依赖性磷酸化。在人角质形成细胞培养物中，p38MAPK抑制剂阻止了PV IgG诱导的HSP27磷酸化，更重要的是，阻止了与细胞间粘附丧失相关的早期细胞骨架变化。进行这项研究是为了 (i) 确定p38MAPK和HSP25 (鼠HSP27同源物) 在PV的体内模型中是否被类似地磷酸化，以及 (ii) 研究p38MAPK抑制在阻止水疱形成中的潜在治疗用途。PV的动物模型。我们现在报道p38MAPK抑制剂在体内预防了PV起泡病。通过抑制角质形成细胞桥粒信号传导靶向终末器官可能对治疗桥粒自身免疫性水疱性疾病有效。

BACKGROUND & AIMS: :A 63-year-old woman had anti-Hu-associated paraneoplastic encephalomyelitis (anti-Hu syndrome) caused by esophageal small cell carcinoma (SCC). The patient developed bilateral limbic encephalitis, followed by myelitis, brain stem encephalitis, and autonomic failure. Extensive examination demonstrated SCC of the abdominal lymph nodes that was retrospectively diagnosed as metastasis of esophageal SCC on autopsy. The neuropathological findings were characterized by widespread neuronal loss and gliosis in the central nervous system, as well as patchy loss of myelin and axons in the spinal nerve roots with perivascular lymphocytic infiltration. This is the first detailed clinical and neuropathological report of anti-Hu syndrome caused by esophageal SCC.

背景与目标： : 一名63岁的女性患有由食管小细胞癌 (SCC) 引起的抗Hu相关的副肿瘤性脑脊髓炎 (抗Hu综合征)。患者出现双侧边缘脑炎，随后出现脊髓炎，脑干脑炎和自主神经功能衰竭。广泛的检查显示腹部淋巴结的SCC在尸检中被回顾性诊断为食管SCC转移。神经病理学发现的特征是中枢神经系统中广泛的神经元丢失和神经胶质增生，以及脊髓神经根中髓鞘和轴突的片状丢失以及血管周围淋巴细胞浸润。这是第一份由食管SCC引起的抗Hu综合征的详细临床和神经病理学报告。

BACKGROUND & AIMS: :Pyodermatitis-pyostomatitis vegetans is a rare mucocutaneous dermatosis often associated with gastrointestinal disorders, especially with inflammatory bowel disease. It is clinically characterized by erythematous lesions with multiple pustules and erosions affecting the mucosal surfaces. Cutaneous lesions are characterized by exudative and vegetating plaques affecting frequently the axillae and groins. The clinical diagnosis is supported by histologic findings, whereas immunofluorescence studies are useful to rule out other entities such as pemphigus3. Herein we report the case of a young man who was misdiagnosed as having IgA pemphigus for 8 years due to positive immunofluorescence findings. The clue for the final diagnosis was the diagnosis of a concomitant ulcerative colitis, which prompted us to reconsider his cutaneous disease.

背景与目标： : 脓性皮炎-脓性口炎是一种罕见的粘膜皮肤皮肤病，通常与胃肠道疾病有关，尤其是炎症性肠病。临床特征为红斑病变，并有多个脓疱和糜烂影响粘膜表面。皮肤病变的特征是渗出性和植被性斑块经常影响腋窝和腹股沟。组织学发现支持临床诊断，而免疫荧光研究可用于排除其他实体，例如天疱疮3。在此，我们报告了一名年轻人的病例，该男子由于免疫荧光阳性发现而被误诊为IgA天疱疮8年。最终诊断的线索是伴随溃疡性结肠炎的诊断，这促使我们重新考虑他的皮肤疾病。

BACKGROUND & AIMS: :Pemphigus vulgaris (PV) is considered to be an autoimmune disease affecting skin and mucous membranes. Traditionally, PV autoantibodies are thought to recognize antigens located in the intercellular substance (ICS) of keratinocytes; antigens represented mainly by the desmosomal cadherin desmoglein 3 (Dsg3). Accordingly, titres of anti-ICS and anti-Dsg3 immunoglobulin G (IgG) are considered to be major laboratory criteria when making a diagnosis of PV. In this paper, we demonstrated for the first time that PV IgG bind antigen(s) expressed on the surface of peripheral blood mononuclear cells (PBMC), as revealed by immunofluorescence studies. This novel autoantigen is immunoprecipitated by PV IgG as a 130 000 molecular weight protein. However, Western blot analysis of the immunocomplexes failed to show reactivity with anti-Dsg3 monoclonal and polyclonal antibodies. Taken together, our data provide strong evidence that PV autoimmunity targets a 130 000 antigen other than Dsg3 on PBMC. This shifting from epidermis to blood cells may open new perspectives for a better understanding of pemphigus autoimmunity and more rational approaches to its treatment.

背景与目标： : 寻常型天疱疮 (PV) 被认为是一种影响皮肤和粘膜的自身免疫性疾病。传统上，PV自身抗体被认为识别位于角质形成细胞的细胞间物质 (ICS) 中的抗原; 主要由桥粒钙粘蛋白桥粒蛋白3 (Dsg3) 代表的抗原。因此，当进行PV的诊断时，抗药和anti-Dsg3免疫球蛋白G (IgG) 的滴度被认为是主要的实验室标准。在本文中，我们首次证明了PV IgG结合外周血单核细胞 (PBMC) 表面表达的抗原 (s)，如免疫荧光研究所揭示的。这种新的自身抗原被PV IgG作为130 000分子量蛋白免疫沉淀。然而，免疫复合物的Western印迹分析未能显示与anti-Dsg3单克隆和多克隆抗体的反应性。综合起来，我们的数据提供了强有力的证据，证明PV自身免疫靶向PBMC上除Dsg3以外的130 000抗原。从表皮到血细胞的这种转变可能为更好地理解天疱疮自身免疫和更合理的治疗方法开辟新的视角。