Research progress on immunologic skin diseases in China / 中国免疫学杂志

Immunologic skin diseases encompass a spectrum of immune system-mediated autoimmune or inflammatory skin conditions,such as lupus erythematosus,psoriasis,atopic dermatitis,and vitiligo.Immunologic skin diseases are characterized by an unclear pathogenesis,complex disease processes,diverse clinical manifestations,and treatment difficulties,thereby presenting sig-nificant diagnostic and therapeutic challenges.Notably,Chinese researchers have achieved numerous innovative research findings on immunologic skin diseases in recent years.Over the past decade,Chinese scholars have contributed 11 919 SCI papers to the field of immune dermatosis,with more than 10 being published in the world's leading medical journals.These publications include one in Sci-ence,one in Nature,two in Cell,three in The New England Journal of Medicine,two in The Lancet,and one in Nature Medicine,as well as four in Immunity.Here,we aim to present a comprehensive summary of Chinese research progress pertaining to the pathogene-sis,diagnosis and treatment of immunologic skin diseases.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

The critical importance of epigenetics in autoimmune-related skin diseases / 医学前沿

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

Research advances in systemic lupus erythematosus in 2022 / 中华皮肤科杂志

Systemic lupus erythematosus has always been a research hotspot in the field of autoimmune diseases in China and other countries. In 2022, Chinese and international researchers have made a lot of new progress in epidemiology, pathogenesis, diagnosis and evaluation, and treatment of systemic lupus erythematosus. This review mainly summarizes major representative advances.

Exploring the application of inquiry-based defensive teaching based on the internet and clinical resources during probationary teaching of dermatovenereology / 中华皮肤科杂志

As a clinical compulsory course, dermatovenereology is characterized by various diseases, complex etiology, and distinct morphological characteristics, and its teaching during the probation period is faced with many challenges. Based on today′s rich educational resources on the internet, and combined with rich clinical resources in large hospitals, the traditional teacher-led lecturing during the probation period needs to be changed, and the adoption of inquiry-based defensive teaching mode has obvious advantages over the traditional teacher-led teaching mode. In the inquiry-based defensive teaching mode, clinical teachers design a series of clinical questions based on clinical topics, then introduce network teaching videos to students to change classroom teaching into students′ after-class learning, induce students to actively explore issues, encourage them to work together in groups to excavate clinical resources, make presentations and organize defense. This teaching mode turns the traditional teacher-led probationary class into a student-led and teacher-assisted speculative defense session, thereby improving learning efficiency and quality, and promoting the cultivation of students′ core literacy and comprehensive ability. Undergraduates are the main target group of this teaching mode, and this mode can also be adopted in the teaching of postgraduates and resident doctors in the standardized training program for the organization of teaching activities and optimization of assessment modes.

Research advances in systemic lupus erythematosus in 2021 / 中华皮肤科杂志

In 2021, Chinese and international researchers have made a lot of new progress in pathogenesis, diagnosis and evaluation, and treatment of systemic lupus erythematosus. This review summarizes major representative advances.

Research advances in systemic lupus erythematosus in 2020 / 中华皮肤科杂志

The etiology of systemic lupus erythematosus is still unclear, and its pathogenesis is complicated. In 2020, Chinese and international researchers made a lot of new progress in the pathogenesis, diagnosis and evaluation, and treatment of systemic lupus erythematosus. This review summarizes major representative advances.

Clinical analysis of 1 057 patients with critical illnesses in a dermatological ward / 中华皮肤科杂志

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

Diagnosis and treatment of adult-onset Still′s disease / 中华皮肤科杂志

Adult-onset Still′s disease (AOSD) is a type of systemic inflammatory disease of unknown etiology, with diverse clinical manifestations, and there are some difficulties in its diagnosis and treatment. In recent years, it has been found that some new markers, such as heme oxygenase 1, calreticulin, inflammatory cytokines and advanced glycation end products, can be used for a comprehensive assessment of the activity and severity of AOSD. Moreover, new biological agents, such as tumor necrosis factor inhibitors, interleukin-1 (IL-1) inhibitors, IL-6 inhibitors and recombinant IL-18 binding proteins, bring new hope for the treatment of AOSD. This review mainly summarizes progress in the diagnosis and treatment of AOSD.

Advances in systemic lupus erythematosus in 2019 / 中华皮肤科杂志

Systemic lupus erythematosus (SLE) is an autoimmune disease that mainly affects young and middle-aged women. It can involve multiple organ systems, with complex and diverse clinical manifestations. The research on the etiology, diagnosis and treatment of SLE has always been a hot spot in this field. In 2019, a lot of new progress was made in the pathogenesis, diagnosis and evaluation, and treatment of SLE in China and other countries, and this review summarizes main representative advances.

Advances in therapeutic targets-related study on systemic lupus erythematosus / 中南大学学报(医学版)

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.

Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NF{kappa}B, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

Successful treatment of three cases of livedoid vasculopathy with rivaroxaban alone or in combination / 中华皮肤科杂志

Livedoid vasculopathy is a rare chronic ischemic necrotic skin disease caused by microvascular thrombosis in superficial vascular plexuses.Effective treatments are lacking.Efficacy of anticoagulants has been clinically proven in the treatment of this disease,but the administration route and adverse reactions limit their extensive application.The new oral factor Xa inhibitor rivaroxaban,which has many advantages,such as no need for coagulation monitoring,few adverse reactions and convenient oral administration,can be used in the prevention and treatment of thrombosis and post-thrombotic ulcers.In this article,3 patients with livedoid vasculopathy were treated with rivaroxaban alone or in combination,and satisfactory efficacy was obtained.

Advances in systemic lupus erythematosus in 2018 / 中华皮肤科杂志

Systemic lupus erythematosus (SLE) is a complex autoimmune disease mainly involving young and middle-aged women, with various clinical manifestations and complicated pathogenesis. SLE has always been a hot spot in the field of autoimmune diseases. This review summarizes new achievements and advances in genomics and clinical studies in SLE in 2018.

Efficacy of combined lymphoplasma exchange for the treatment of severe refractory immune-related skin diseases: a clinical observation / 中华皮肤科杂志

Objective To evaluate the clinical efficacy of lymphoplasma exchange (LPE) for the treatment of severe refractory immune-related skin diseases.Methods From May 2013 to October 2015,8 patients with toxic epidermal necrolysis,drug-induced hypersensitivity syndrome (DIHS),pemphigus vulgaris,pemphigoid or paraneoplastic pemphigus were enrolled from Department of Dermatology,Xiangya Hospital,Central South University,who showed no response to conventional therapy or presented with multiple organ dysfunction.After the treatment with LPE,the efficacy was evaluated,and adverse reactions were observed.Results After one session of LPE therapy,6 patients received marked improvement,and were cured at last.In 1 patient with pemphigus vulgaris who was resistant to the treatment with high doses of glucocorticoids and immunosuppressive agents,the rashes regressed during the treatment with LPE,but recurred after the end of treatment.One patient with bullous pemphigoid presented with eruptive blisters on the next day after the treatment with LPE,which were considered as allergic reactions to allogeneic plasma.There were no obvious differences in white blood cell count,lymphocyte count,neutrophil count and blood platelet count in the peripheral blood of 8 patients before and after the treatment with LPE.During the follow-up of 3-5 years,all of the patients were recovered without recurrence,except 1 patient with bullous pemphigoid who died of disseminated tuberculosis after 1 year.Conclusion LPE is effective for the treatment of severe immune-related skin diseases,but attention should be paid to potential transfusion reaction and allergic reactions.

A rare case report for dermatomyofibroma in nasion / 中南大学学报(医学版)

Dermatomyofibroma is a benign and rare proliferation of myofibroblasts and fibroblasts of the skin.Dermatomyofibroma commonly locates at the shoulder and neck of young adults and adolescents.Other frequently affected anatomic sites are upper arms,thigh,chest wall,back,axillary region and abdomen.Herein,we reported a case of dermatomyofibroma occurred in the nasion.The asymptomatic firm nodule and histopathological features were consistent with dermatomyofibroma.Immunohistochemically,the tumor cells expressed vimentin,HHF35 and α-smooth muscle actin (α-SMA).The patient was followed up for 2 years after excision of the tumors and recurrences were not observed.

A case report of subcutaneous panniculitis-like T cell lymphoma with fever and erythema on the body as the initial symptoms / 中南大学学报(医学版)

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare form of peripheral α/β T cell skin lymphoma that is localized primarily in the subcutaneous adipose tissues.It is characterized by single or multiple painful subcutaneous nodules or lumps,often affecting the limbs.The patient presented to the Department of Dermatology,Second Xiangya Hospital,Central South University,who suffered from intermittent fever and erythema on the body,finally was diagnosed as SPTCL after histopathological examinations for twice.

A case of nasal NK/T-cell lymphoma / 中南大学学报(医学版)

A 29-year-old male patient with extranodal NK/T-cell lymphoma,a nasal type lymphoma with involvement of skin as the first symptom,was reported.The patient presented with swelling in the left side of the nose and suffered intermittent fever for 1 month.The fester in the oral mucosa and skin under the left nostril and redness,and the swelling on the orbit of the left eye lasted for 1 week.Physical examination showed that the left side of nose was swelling,and the skin below the left nostril was anabrotic and crusted.There were different ulcers in his jaws and buccal mucosa.Bilateral eyelid was redness and swelling,especially in the left side.Binocular conjunctival was congestive.The diagnosis of extranodal NK/T-cell lymphoma (nasal type) was confirmed by biopsy and immunohistochemistry.

Current research on pathogenesis and treatment of atopic dermatitis / 中国医师杂志

Atopic dermatitis (AD) is an allergic skin disease with a genetic predisposition.The pathogenesis is complex,including environment stimulation,epidermal barrier deficiency,and autoimmune disorders.The destruction of epidermal barrier stimulates the inflammatory response.In acute period,Th2 cells are activated to produce IL-4 and induce B lymphocytes to secrete IgE.Thus leads to degranulation of mast cells and basophils.After acute period,epidermis is thickened,accompanied with increasing expression levels of several chemokines and cytokines.In chronic phase,the cellular infiltration includes mainly Th1 and Th2 cells,and less Th17 and Th22 cells.The latter two cells together with their specific cytokines and chemokines are derived from keratinocytes and fibroblasts,which can produce tissue remodeling and fibrosis.So far,the treatment of AD contains allergens exposure avoid,anti-inflammatory,anti-infection,phototherapy,and immune therapy,etc.

Th17 cells and psoriasis / 中国医师杂志

Psoriasis is a common autoimmune disease and mainly affects skin,joints,or both.Psoriasis is also a chronic relapsing disorder that can cause physical and psychological burdens to patients.Currently it is widely accepted that the immune system is involved in the development of psoriasis.Th17 cells,a subtype of CD4 +T lymphocytes,are characterized by its ability to secrete proinflammatory cytokine IL-17.Recent studies indicate that Th17 cells play a predominant role in the pathogenesis of psoriasis and other immune-mediated inflammatory diseases.Moreover,targeted therapies have been developed and approved for the treatment of moderate-to-severe plaque psoriasis or psoriatic arthritis.This review summarizes the role of Th17 cells in the pathogenesis of psoriasis and several therapeutic biologics targeting this pathway in psoriasis.