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Xanthoma disseminatum (XD) is a rare non-Langerhans cell histiocytosis characterized by xanthomatous lesions in the absence of hyperlipidemia. XD usually develops in young adults, and there are rare cases among children. BRAF mutations are frequent in Langerhans cell histiocytosis and Erdheim-Chester disease but absent or only rarely detected in other histiocytosis. Herein, we described a 6-year-old Chinese girl presented with generalized skin lesions and diabetes insipidus for 5 months. There were multiple periorbital xanthelasma with histopathological features of foamy histiocytes infiltration with Touton cells. Pituitary magnetic resonance imaging showed pituitary enlargement and pituitary stalk thickening. The presence of BRAF p.V600E mutation makes this case distinctive and also offers a potential therapeutic target. According to our review of the literature, this is the first pediatric XD with diabetes insipidus and BRAF mutation.

Rosai-Dorfman disease (RDD, also known as sinus histiocytosis with massive lymphadenopathy) is a rare and benign non-Langerhans cell histiocytosis. Skin biopsy usually shows nodular or diffuse dermatitis. Rosai-Dorfman cells (RDD cells) and emperipolesis are the key to diagnosis. RDD cells express S-100 antigen, CD68, CD163, α1-antitrypsin, α1-antichymotrypsin, and ham-56, whereas Langerhans cell markers such as CD1a and langerin are negative. We presented a case of a 55-year-old man with varying sizes of many dark red nodules and lumps over the face, trunk, and limbs for approximately 1 year but without systemic involvement. The results of the laboratory evaluations were notable for an increased level of serum IL-6 and serum IgG4. Histopathological examination showed a diffused dense nodular infiltration of "nude" epithelioid histiocytes with infiltration of minimal lymphocytes and plasm cells around the epithelioid nodules. Immunohistochemistry identified nodular histiocytes being stained strongly positive for S-100 and CD68 but negative for CD1a. Plasma cells showed focally positive for IgG, IgG4, and CD38 and with a ratio of IgG4/IgG >40%. Considering these findings, we believe that our case meets the diagnostic description of "cutaneous Rosai-Dorfman disease" and is, therefore, a rare case with clinical features of multiple tumor-like nodules, sarcoidosis-like histological features, and immunohistochemistry of IgG4-positive plasma cells.

Hidrotic ectodermal dysplasia (HED) is a rare inherited syndrome characterised by nail dystrophy, palmoplantar hyperkeratosis and alopecia. Four mutations (p.G11R, p.A88V, p.V37E and p.D50N) in gap junction beta 6 (GJB6) gene, which codes connexin30 protein, have been found to cause HED in different populations. Here, we reported a big Chinese family in which 24 patients over five generations were suffered with HED. Sequence analysis identified all 24 patients carry a recurrent missense mutation c.263C > T (p.A88V) in GJB6. Our results reveal gene testing of GJB6 is important for diagnosis, prenatal diagnosis and future gene treatment of HED.

Generalized eruptive histiocytoma (GEH) is a very rare benign disorder belonging to the group of non-Langerhans cell histiocytosis (non-LCH). GEH is characterized by a nearly uniform infiltrate of histiocytes with classic immunological phenotype (CD68+, S-100- and CD1a-). Prominent eosinophilic infiltration and S100-positive histiocytes are rarely associated in GEH. In this article, we reported a middle-age man presented with disseminated reddish papules distributed on the trunk and proximal extremities. A skin biopsy of the papule showed a dense histiocytic infiltration with prominent eosinophils. By immunohistochemistry, the histiocytes revealed strongly positive for CD68 and S100 protein and negative for CD1a and Langerin (CD207). Based on clinical and histopathological criteria, the diagnosis of GEH was established. We presented this rare case of GEH with such distinctive features to strengthen the awareness of this uncommon form of non-LCH. Classical histopathological and immunological features cannot reliably distinguish GEH from other non-LCH.

ObjectiveLupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus.MethodsThis is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case–control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed.ResultsA total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups.ConclusionsCLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren’s syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren’s syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

Systemic lupus erythematosus (SLE) is a chronic and autoimmunity-mediated diffuse connective tissue disease. The mainstay of treatments for SLE mainly relies on corticosteroids and immunosuppressants, which have a series of unavoidable side effects. Therefore, it is of fundamental importance to search novel therapeutic targets for better treatment with favorable efficacy and minor side effects. Recent studies shed light on potential therapeutic targets for SLE, mainly covering the followings: B-cell/plasmocyte-related targets [B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD20, CD22, CD19/FcγRIIb, Bruton tyrosine kinase (Btk), and proteasome], T cell-related targets [calcineurin, mammalian target of rapamycin (mTOR), regulatory factor X1 (RFX1), and Rho kinase], macrophage-related targets (macrophage migration inhibitory factor), intracellular signaling molecules, cytokines (cereblon, histone deacetylase 6, Janus activated kinase/signal transducer and activator of transcription), co-stimulating factors (CD28/B7, CD40/CD154), IgE autoantibody, and gut microbiome. Among them, belimumab (a humanized monoclonal antibody against B-lymphocyte stimulator) and telitacicept (a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein) have been sequentially approved for the clinical treatment of SLE in China. A variety of new targeted-therapy drugs are in the Phase 2 or Phase 3 clinical trials,among which anifrolumab (a human monoclonal antibody against type I interferon receptor subunit 1) has completed a Phase 3 clinical trial with good responses achieved, although its incidence of herpes zoster is higher than that in the control group. The research progress in both molecular mechanisms and new drug development for different therapeutic targets have greatly promoted our better and in-depth understanding of the pathogenesis of SLE, and have also reflected the complexity and heterogeneity of the disease. Successful development and clinical application of more novel therapies would no doubt usher in a new era of individualized treatment for SLE in the future.系统性红斑狼疮(systemic lupus erythematosus，SLE)是一种自身免疫介导的慢性弥漫性结缔组织病。目前SLE的治疗主要依赖糖皮质激素及免疫抑制剂，但长期使用这些药物存在诸多难以避免的毒副作用。因此，寻找新型治疗靶点对于探索特异性更强、毒副作用更小的新疗法具有重要意义。目前对SLE治疗的研究，主要涉及B细胞/浆细胞相关靶点(如B淋巴细胞刺激因子、增殖诱导配体、CD20、CD22、CD19/FcγRIIb、Bruton酪氨酸激酶、蛋白酶体)、T细胞相关靶点(如钙调磷酸酶、哺乳动物雷帕霉素靶蛋白、调节因子X1、Rho激酶)、巨噬细胞相关靶点(如巨噬细胞游走抑制因子)、细胞内信号分子(如Cereblon、组蛋白去乙酰化酶6、Janus激酶/信号转导与转录激活因子等)、共刺激因子(如CD28/B7、CD40/CD154)、细胞因子(如IL-2、IL-12/23、IL-10、IL-6、干扰素)、IgE以及肠道菌群等方面。其中，针对B细胞/浆细胞相关靶点的贝利尤单抗(人源化抗B淋巴细胞刺激因子单克隆抗体)、泰它西普(重组人B淋巴细胞刺激因子受体-抗体融合蛋白)已在我国相继获批用于SLE的临床治疗。还有多种靶向治疗新药处在II期或III期临床试验阶段，其中，Anifrolumab(抗I型干扰素受体亚基1的全人单克隆抗体)已完成III期临床试验并取得良好应答，但其带状疱疹发生率高于对照组。近年来，这些针对不同靶点的基础研究和新药研发大大推动了医学界对SLE发病机制认识的深入，也反映出该病的复杂性和异质性。随着更多新疗法投入使用，未来有望迎来SLE个体化治疗的崭新局面。.

Skin disorders are a large family of various complex diseases and dysfunctions. With the development of epigenetics in human diseases, more and more skin disorders were proved to be associated with epigenetic modifications. Defined as heritable changes in gene expression that do not involve a change in the genomic DNA sequence, epigenetics may play a significant role and open a new window in skin disorders. In this chapter, we summarize the epigenetic modifications of a number of skin disorders including immunologic skin diseases, infectious skin diseases, skin tumors, and skin aging. We also review a number of candidate epigenetic markers and potential therapeutic strategies. Understanding the concepts of epigenetics can provide insights into the pathogenesis of skin disorders, and may lead to the development of biomarkers, improve prognosis, and support the development of novel molecular targets in therapies, especially refractory skin diseases. Epigenetics will serve as the next large area of medicine with the potential to treat and possibly prevent skin diseases in the future.

Systemic lupus erythematosus (SLE) is a common autoimmune disease with high incidence in females. The pathogenesis of SLE is complex, and healing SLE has become a serious challenge for clinical treatment. Aberrant expression of miR-301a-3p involves the progressions of multiple diseases, and some studies have indicated that increased miR-301a-3p could induce the inflammatory injury of some organs. However, the role and molecular mechanism of miR-301a-3p in SLE remain unclear. In this study, the miR-301a-3p levels in peripheral blood mononuclear cells (PBMCs) of the patients with SLE and health subjects were measured with qRT-PCR. The ELISA assay was used to investigate the effect of miR-301a-3p on the levels of inflammatory factors in PBMCs, and flow cytometry assays were used to observe the effect of miR-301a-3p on the levels of CD4+ T cells and Th17 cells in PBMCs. Moreover, TargetScan, dual-luciferase reporter assay, and western blot were used to reveal the downstream targets and regulation mechanism of miR-301a-3p in SLE. The results showed that miR-301a-3p was significantly upregulated in PBMCs of the SLE patients, and increased miR-301a-3p could boost the expression of IL-6, IL-17, and INF-γ in PBMCs and promote the differentiation of Th17 cells. It was found that PELI1 was a target of miR-301a-3p, and PELI1 upregulation could effectively reverse the effect of miR-301a-3p on PBMCs. Besides, this study also found that miR-301a-3p could promote the expression of IRAK1 to involve the progression of SLE via targeting PELI1. In conclusion, this study suggests that increased miR-301a-3p serves as a pathogenic factor in SLE to promote IRAK1-mediated differentiation of Th17 cells via targeting PELI1.

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR’97), 2012 Systemic Lupus International Collaborating Clinics (SLICC’12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR’19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC’12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR’19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.

Systemic lupus erythematosus (SLE) is a multi-system-involving autoimmune disorder mainly affecting young and middle-aged women. Autoantibodies formation and immune complex deposition as well as other immune mechanisms contribute to heterogeneous clinical presentation, which leads to challenges for diagnosis and management. Although the exact pathogenesis of SLE is highly complicated, the pathophysiological understanding of SLE is constantly evolving and relevant studies were continually published, providing a better understanding of the molecular mechanisms. Moreover, new therapeutic strategies and management plans targeting pivotal factors involved in the pathogenesis of SLE got well established recently. In this article, we reviewed recent studies to provide an update in understanding pathogenesis and therapeutic strategies of SLE.

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Supplemental material, sj-pdf-1-lup-10.1177_0961203320959716 for A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum by Hui Jin, Tao Huang, Ruifang Wu, Ming Zhao, Haijing Wu, Hai Long, Heng Yin, Jieyue Liao, Shuangyan Luo, Yu Liu, Qing Zhang, Peng Zhang, Yixin Tan, Shuaihantian Luo, Xin Huang, Yaxiong Deng, Wei Liao, Liu Duan, Jianbo Chen, Yin Zhou, Jinghua Yin, Hong Qiu, Jin Yuan, Zijun Wang, Mengying Li, Xiaoqi Wu, Lina Chen, Liangmin Cai, Cancan Huang, Qianwen Li, Bingsi Tang, Bihui Yu, Xin Li, Xiaofei Gao, Yixi Hu, Xiaolei Ren, Haofan Xue, Zhangming Wei, Jinwei Chen, Fen Li, Guanghui Ling, Hui Luo, Hongjun Zhao, Sen Yang, Yong Cui, Youkun Lin, Xu Yao, Lingyun Sun, Qing Guo, Hong Fang, Kang Zeng, Danqi Deng, Jianzhong Zhang, Yuzhen Li, Xiongming Pu, Xiangping Liao, Xiqiang Dang, Danlin Huang, Yumei Liang, Qing Sun, Hongju Xie, Li Zeng, Cibo Huang, Qingchun Diao, Juan Tao, Jianbin Yu, Zhenlu Li, Hanshi Xu, Hui Li, Wei Lai, Xiguang Liu, Jingjing Wu, Tienan Li, Tiechi Lei, Qiuning Sun, Yanjia Li, Guoqiang Zhang, Xin Huang and Qianjin Lu in Lupus

Supplemental material, sj-pdf-2-lup-10.1177_0961203320959716 for A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum by Hui Jin, Tao Huang, Ruifang Wu, Ming Zhao, Haijing Wu, Hai Long, Heng Yin, Jieyue Liao, Shuangyan Luo, Yu Liu, Qing Zhang, Peng Zhang, Yixin Tan, Shuaihantian Luo, Xin Huang, Yaxiong Deng, Wei Liao, Liu Duan, Jianbo Chen, Yin Zhou, Jinghua Yin, Hong Qiu, Jin Yuan, Zijun Wang, Mengying Li, Xiaoqi Wu, Lina Chen, Liangmin Cai, Cancan Huang, Qianwen Li, Bingsi Tang, Bihui Yu, Xin Li, Xiaofei Gao, Yixi Hu, Xiaolei Ren, Haofan Xue, Zhangming Wei, Jinwei Chen, Fen Li, Guanghui Ling, Hui Luo, Hongjun Zhao, Sen Yang, Yong Cui, Youkun Lin, Xu Yao, Lingyun Sun, Qing Guo, Hong Fang, Kang Zeng, Danqi Deng, Jianzhong Zhang, Yuzhen Li, Xiongming Pu, Xiangping Liao, Xiqiang Dang, Danlin Huang, Yumei Liang, Qing Sun, Hongju Xie, Li Zeng, Cibo Huang, Qingchun Diao, Juan Tao, Jianbin Yu, Zhenlu Li, Hanshi Xu, Hui Li, Wei Lai, Xiguang Liu, Jingjing Wu, Tienan Li, Tiechi Lei, Qiuning Sun, Yanjia Li, Guoqiang Zhang, Xin Huang and Qianjin Lu in Lupus

Pemphigus vulgaris is an autoimmune blistering disease characterized by a loss of epidermal cell–cell adhesion caused by anti-desmoglein (Dsg) autoantibodies. The pathogenesis of PV remains unclear. However, abnormal frequency and function of Th2 cells are believed to contribute to PV. We investigated Nr4a2, a transcription factor, which has been found to regulate T cell differentiation, for its association with Th2 cell differentiation and functions in PV. We found significantly decreased mRNA and protein levels of Nr4a2 in CD4+ T cells from patients with PV, compared with healthy control subjects. In addition, mRNA and protein levels of Nr4a2 in CD4+ T cells were inversely correlated with serum levels of IL-4 and IL-13 in patients with PV. Overexpression of Nr4a2 in CD4+ T cells from patients with PV significantly reduced the mRNA levels of GATA3, IL-4, and IL-13, while Nr4a2 siRNA treatment showed the reverse effects on the expression of these Th2-related cytokines and transcription factors. The data suggest that the altered level of Nr4a2 in CD4+ T cells is associated with the development of PV. Nr4a2 may contribute to the pathogenesis of PV by negatively regulating Th2 activity and secretion of Th2-related cytokines.

Background As the booming of deep learning era, especially the advances in convolutional neural networks (CNNs), CNNs have been applied in medicine fields like radiology and pathology. However, the application of CNNs in dermatology, which is also based on images, is very limited. Inflammatory skin diseases, such as psoriasis (Pso), eczema (Ecz), and atopic dermatitis (AD), are very easily to be mis-diagnosed in practice. Methods Based on the EfficientNet-b4 CNN algorithm, we developed an artificial intelligence dermatology diagnosis assistant (AIDDA) for Pso, Ecz & AD and healthy skins (HC). The proposed CNN model was trained based on 4,740 clinical images, and the performance was evaluated on experts-confirmed clinical images grouped into 3 different dermatologist-labelled diagnosis classifications (HC, Pso, Ecz & AD). Results The overall diagnosis accuracy of AIDDA is 95.80%±0.09%, with the sensitivity of 94.40%±0.12% and specificity 97.20%±0.06%. AIDDA showed accuracy for Pso is 89.46%, with sensitivity of 91.4% and specificity of 95.48%, and accuracy for AD & Ecz 92.57%, with sensitivity of 94.56% and specificity of 94.41%. Conclusions AIDDA is thus already achieving an impact in the diagnosis of inflammatory skin diseases, highlighting how deep learning network tools can help advance clinical practice.

Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors.

Systemic lupus erythematosus (SLE) is a severe autoimmune disease that causes multiple-organ dysfunction mainly affecting women in their childbearing years. Type I IFN synthesis is usually triggered by viruses, and its production is tightly regulated and limited in time in health individuals. However, many patients with systemic autoimmune diseases including SLE have signs of aberrant production of type I interferon (IFN) and display an increased expression of IFN-inducible genes. Continuous type I IFNs derived from activated plasmacytoid dendritic cells (pDCs) by interferogenic immune complexes (ICs) and migration of these cells to tissues both break immune tolerance and promote an on-going autoimmune reaction in human body. By the means of detecting type I IFNs and IFN-inducible genes, it can help with diagnosis and evaluation of SLE in early stage and more efficiently. Anti-IFN-α monoclonal antibodies in SLE patients were recently reported and is now being investigated in phase II clinical trails. In this review, we focus on recent research progress in type I IFN and IFN-inducible genes. Possible mechanisms behind the dysregulated type I IFN system in SLE and how they contribute to the development of an autoimmune process, and act as a biomarker and therapeutic target will be reviewed.

Adiponectin is a circulating hormone with pleiotropic functions in lipid and glucose metabolism secreted by adipocytes. It plays a beneficial role in cardiovascular functions and metabolic complications. Recently, growing researches have elucidated that increased adiponectin plasma levels correlate with severity of rheumatoid arthritis (RA) and it is speculative that adiponectin may link to RA. The association of adiponectin with potential inflammatory functions in RA has raised significant interests in exploring this adipokine as a target for RA-diagnostic and therapeutic applications. Despite significant advances in understanding adiponectin functions and signaling mechanisms, its roles in RA remain multifaceted and subject to controversy. This review highlights the evidences linking adiponectin to either anti-inflammatory or pro-inflammatory action in RA. The results of this review may provide important insight into adiponectin in the development of RA.