Elastosis perforans serpiginosa. Considerations on the pathogenesis based on a typical case]

Elastosis perforans serpiginosa (EPS) is a rare entity belonging to the group of primary perforating dermatoses. A 13-year-old male patient with Down's syndrome developed reddish hyperkeratotic papules in a serpiginous and ellipsoid configuration on the face. Histological examination revealed transepidermal elimination of thick coarse elastic fibres from the papillary dermis. The dermal infiltrate showed an immunohistological pattern consistent with an acute cell-mediated immune response. It consisted mainly of activated T-lymphocytes, with a predominance of CD4-positive cells. Considerable numbers of CD1-positive cells were also present. Inflammatory macrophages of the 27E10 phenotype were found in considerable numbers, whereas 25F9-positive resident macrophages were almost completely absent. The role of a cell-mediated immune response in the mechanism of transepithelial elimination is discussed.     

Neurofibromatosis--new clinical and molecular genetic aspects]

Neurofibromatosis is not a single entity. Seven types of the disorder are now known, which can be differentiated by clinical and genetic features. The wide variety of clinical manifestations makes close interdisciplinary cooperation necessary, in which the dermatologist frequently has a key role. The most frequent forms are peripheral neurofibromatosis (NF1) and central neurofibromatosis (NF2), for which separate gene localizations have been found on chromosomes 17 and 22, respectively, by molecular genetics techniques. The meanwhile possible prenatal diagnosis raises ethical questions.     

关节病性银屑病遗传学发病机制和治疗进展

关节病性银屑病是一种慢性炎症性关节病变,与该病发病显著相关的易感基因或易感位点有IL-23R、IL-12B、HLA-Cw6、TRAF3IP2、NO、FBXL19、PSMA6-NFKBIA附近区域,可能相关的易感基因有IL-23A、TNIP1、TNF*-857T、LCE3C-LCE3Bdel变异体、REL基因、IL-13.针对关节病性银屑病发病环节中的一些重要免疫分子或免疫细胞,多种靶向生物制剂包括细胞因子拮抗剂(英夫利西、益赛普、阿达木、戈利木、优斯它单抗)、磷酸二酯酶抑制剂、T细胞抑制剂(阿贝西普)和B淋巴细胞耗竭剂(利妥昔单抗)用于该病的治疗,疗效好,安全性较高.     

New studies on the pathogenesis of lupus erythematosus]

The pathogenesis of the lupus erythematosus results from co-operation of three principles: (1) genetical disposition, (2) increased reactivity of the immune system, (3) different exogenic influences. The genetical disposition is confirmed by family investigations, metabolic disorders and immune anomalies as well as by parallels to animal models. The reaction manner of the immune system is genetically determined. Exogenic factors influence the immune system (behaviour) either as starter or by modifying the genetical material. The most striking humoral immune phenomenon is an immense number of (auto-)antibodies. Investigations of xeroderma pigmentosum as well as with DNA of different antigenity have shown that an increase of the antigenicity is unlikely for this phenomenon. In the serum of patients there were established and partially characterized factors (mitogens, granulocytic adherence-factor) for increasing the immune reactivity. The increase of such factors may be the sequence of a T-suppressor cell-defect. Like-wise no interdigitating cells in systemic lupus erythematosus have been found, cells which may be responsible for the terminal differentiation of T-lymphocytes. The mode of action of exogenic factors is represented and discussed with the example of the UV provocation.     

Ultrastructure and molecular pathogenesis of epidermolysis bullosa

Epidermolysis bullosa (EB) is classified into the three major subtypes depending on the level of skin cleavage within the epidermal keratinocyte or basement membrane zone. Tissue separation occurs within the intraepidermal cytoplasm of the basal keratinocyte, through the lamina lucida, or in sublamina densa regions of the basal lamina (basement membrane) in EB simplex, junctional EB, and dystrophic EB, respectively. Transmission electron microscopy (TEM) is an effective method for determining the level of tissue separation and hemidesmosome (HD) and anchoring fibril morphology if performed by experienced operators, and has proven to be a powerful technique for the diagnosis of new EB patients. Recent advances in genetic and immunofluorescence studies have enabled us to diagnose EB more easily and with greater accuracy. This contribution reviews TEM findings in the EB subtypes and discusses the importance of observations in the molecular morphology of HD and basement membrane associated structures.     

Muir-Torre syndrome and familial colorectal cancer: 2 families with molecular genetic analysis]

INTRODUCTION: The Muir-Torre Syndrome is a rare genodermatosis, defined by the occurrence of cutaneous tumors (such as sebaceous adenomas, epitheliomas, or carcinomas, and/or keratoacanthomas), and internal malignancies. Recently, molecular analysis in hereditary non polyposis colorectal cancer demonstrated a common genetic basis, linking these two disorders, with the observation of germline mutations in the hMSH2 gene (one of the DNA mismatch repair system genes) in both syndromes. Such molecular demonstration of a single nosological entity should be clinically used to improve the indications of molecular testings in oncogenetics, still restricted to highly stringent criteria for hereditary non polyposis colorectal cancer. CLINICAL CASES: We identified three patients from two different families, who fulfilled the criteria for both Muir-Torre Syndrome and hereditary non polyposis colorectal cancer. The search of a germline mutation of the hMSH2 gene was performed on an affected member from each family, and their relatives with their informed consent. Within each family, all individuals with colorectal cancer were carriers of the same mutation. In the first family, this mutation was a pathogenic microinsertion, usable for predictive testing. In the second family, a missense mutation was identified, requesting further demonstration of its pathogenicity before its use in a predictive purpose. CONCLUSIONS: The diagnosis of cutaneous tumors compatible with Muir-Torre syndrome should lead the dermatologist to suspect an hereditary non polyposis colorectal cancer that should bring to an oncogenetic approach: personnal and familial history of colorectal cancer, molecular analysis, recommendations for colonoscopic screening in at-risk relatives. In the case of a colorectal cancer at a young age, or in the case of familial cases, the gastroenterologist should screen for cutaneous lesions of Muir-Torre syndrome, which could add a criteria for an hereditary syndrome, and lead to molecular oncogenetic analysis.     

Integrating complement into the molecular pathogenesis of Hidradenitis Suppurativa

Complement inhibition has been identified as a potential therapeutic target for multiple inflammatory disorders including Hidradenitis Suppurativa (HS). It is currently unclear how complement integrates into our current model of molecular pathogenesis in HS and whether it represents a central component of pathogenesis, or a neutrophil-associated bystander. Levels of C5a in serum and tissue correlate with disease activity and degree of neutrophilic infiltrates in HS. C5a has been associated with Th17 immune axis activation in psoriasis, rheumatoid arthritis and Crohn's disease with strong similarities to TH17 activation in HS. Porphyromonas species (which are identified in the HS microbiome) are able to cleave inactive C5 into C5a implicating the cutaneous microbiome as an activator of complement. C3a and C5a are associated with activation of the NLRP3 inflammasome, implicated in the inflammatory drive in HS. Complement receptors are present upon dendritic cells, monocytes, fibroblasts and adipocytes, which may broaden the potential contribution of complement to multiple aspects of HS pathogenesis. Dysregulation of complement receptor pathways has been documented in obesity, insulin resistance and polycystic ovarian syndrome leading to the possibility that complement may explain the epidemiological associations between these conditions and HS. The therapeutic potential of complement inhibitors in HS may be related to the therapeutic target (complement receptor or complement subunit) and the presence of alternate receptors (such as C5aR2) or ligands (including C3a, PAMPs and DAMPs). Integrating complement into the known pathogenesis of HS may aid in explaining the contradictory results between Phase 2 studies of C5a antagonists. It also allows for the identification of existing knowledge gaps to target further clinical investigation and research.     

The genetic epidemiology and autoimmune pathogenesis of alopecia areata

Unlit recently, there was only circumstantial evidence to support the autoimmune and genetic etiology of alopecia areata. The advent of HLA stereotyping and linkage analysis has revealed an increase in specific HLA alleles in patients with alopecia areata and controls. Even more current is the detection of autoantibodies to the hair follicle in the sera from humans with alopecia areata and laboratory animal models of the disease. Recent experiments suggest that there may even be specific HLA class II alleles that play a protective role against the development of alopecia areata. Herein, the circumstantial data and the confirmed linkage data to support a genetic/autoimmune interplay theory of alopecia areata are discussed. The temporal advancements of research in the area of the HLA typing are reviewed for the disease.     

儿童腋窝颗粒状角化不全

报告1例儿童腋窝颗粒状角化不全.患儿女,12岁.左侧腋窝发生红斑、丘疹伴瘙痒10年.组织病理检查示角化过度伴角化不全,并可见透明角质颗粒,颗粒层轻度增厚,表皮突延长.诊断:腋窝颗粒状角化不全.     

Granular parakeratosis in children: case report and review of the literature

Granular parakeratosis is a cutaneous eruption with erythematous and/or brownish hyperkeratotic papules and plaques which are exclusively localized to intertriginous areas and show histopathologic features of an unusual form of parakeratosis. The etiology is unknown, but the excessive use of various topical preparations (e.g., ointments and deodorants) has been associated with this disease. It has heretofore been reported only in adults. We report two children, ages 3 and 5 months, with characteristic lesions in the groin associated with topical pomades used to prevent diaper rash. This is the first report associating the clinical presentation and the histopathologic diagnosis of granular parakeratosis in children. The literature on this entity is also reviewed and all case reports are summarized.     

基于“气血理论”刍议阳痿病机及治法

愈来愈多的男性患者受到阳痿(勃起功能障碍)的困扰,中医药治疗阳痿的历史源远流长,有一定疗效,治痿思路百花齐放。气血理论源于《黄帝内经》,并认为气血调和与否与疾病的发生发展密切相关。中医理论认为正常的勃起需要人体脏腑、经络、气血等的互相协调,五脏协同,经脉通畅,气血充足,则勃起有力而持久。现认为,气血调和是正常勃起功能的基本保障,而气血失和则是阳痿的关键病机,通过益气活血法调治气血也许是治疗阳痿的基本治法。