Clinical characteristics and risk factors of juvenile dermatomyositis with relapses / 中华风湿病学杂志

Objective:To analyze the clinical characteristics and risk factors of juvenile dermatomyositis (JDM) with relapses by comparing clinical features, treatment and disease course among JDM patients with and without relapses.Methods:A retrospective analysis of 102 JDM patients from Children's Hospital of Nanjing Medical University between March 2017 and March 2021 was carried out. Patients were divided into two groups based on whether a JDM relapse had occurred or not. Initial clinical features, laboratory tests and treatment were compared between the two groups. T-test or Mann-Whitney U test was used for measurement data, chi-square test or fisher exact probability was used for count data. The features associated with risk of relapses were analyzed by multivariate logistic regression. Results:Among 102 children with JDM, twenty patients (19.6%) relapsed during drug reduction or after drug withdrawal. The mean duration to the first relapse was 3.24 years (range: 9 months to 7 years). Myositis specific antibodies (MSA) were positive for 8 (40.0%) patients with relapses. With 5 cases were anti-nuclear matrix protein 2 positive, 2 cases were anti-transcription interme-diary factor 1 gamma positive, 1 case was anti-signal recognition particle (SRP) positive, the other 12 cases were MSA negative. By binary logistic regression analysis, we found that peripheral calcinosis [ OR(95% CI)=17.54(1.55, 198.64), P=0.021], and interstitial lung disease [ OR(95% CI)=3.83(1.27, 11.59), P=0.017] were independently related to JDM with relapses. Fifty-three patients (51.9%) received methylpre-dnisolone pulse therapy for initial treatment and 13 (65.0%) patients with relapses received methylprednisolone pulse for initial treatment. There was no significant difference between the two groups ( χ2=1.70 , P=0.193). Tumor necrosis factor alpha antagonist combined with methotrexate (MTX) had achieved good results in clinical treatment in children with relapses. Conclusion:The risk of relapses is high in children with JDM. Calcinosis and interstitial lung disease at disease onset can predict a relapsing disease course. Aggressive treatment is urgently demanded for patients with JDM, especially those with relapses.

Research progress of neutrophil extracellular traps in rheumatic diseases / 中华实用儿科临床杂志

Rheumatic diseases are inflammatory diseases characterized by severe immune dysregulation, which can affect tissues and joints.Neutrophils are the key factor contributing to immune disorders, and they play an important role in rheumatic diseases.Neutrophil extracellular traps (NETs) are network structures released by neutrophil granulocytes when stimulated.As a novel immune defense mechanism, NETs have attracted wide attention.In this paper, the formation, function and role of NETs in rheumatic diseases and other diseases were reviewed.

Research progress of neutrophil extracellular traps in rheumatic diseases / 中华实用儿科临床杂志

Rheumatic diseases are inflammatory diseases characterized by severe immune dysregulation, which can affect tissues and joints.Neutrophils are the key factor contributing to immune disorders, and they play an important role in rheumatic diseases.Neutrophil extracellular traps (NETs) are network structures released by neutrophil granulocytes when stimulated.As a novel immune defense mechanism, NETs have attracted wide attention.In this paper, the formation, function and role of NETs in rheumatic diseases and other diseases were reviewed.

Clinical features of Kawasaki disease shock syndrome and analysis of interleukin-6 expression levels / 中国小儿急救医学

Objective:Kawasaki disease shock syndrome(KDSS) is a serious complication of Kawasaki disease(KD). The main manifestations are low blood pressure and decreased blood perfusion at the acute stage of onset, which is life-threatening.The purpose of this study was to provide early intervention and reduce the complications and mortality of this disease by analyzing clinical features and expression level of interleukin-6(IL-6)of children with KDSS.Methods:In this study, a total of 25 children with KDSS in Nanjing Children′s Hospital were collected, and their clinical characteristics, relevant laboratory indicators and IL-6 expression levels were analyzed by retrospective case-control study.Results:Compared with ordinary KD children, KDSS children were more common in older children, with prolonged fever, severe skin rash, high inflammatory indicators, and more likely to be associated with coronary dilatation.The level of IL-6 in children with KDSS in the acute phase was significantly higher than that in children with KD[(28.5±39.2) ng/mL vs.(226.8±102.9) ng/mL, P<0.05], while the level of IL-6 in children with KDSS in the convalescent period was significantly lower than that in the acute phase of KDSS[(226.8±102.9) ng/mL vs.(5.6±1.7)ng/mL, P<0.05], and the difference was statistically significant. Conclusion:The systemic inflammatory response of KDSS is more obvious, IL-6 plays an important role in it, and the therapeutic effect of IL-6 blocker in KD and its complications needs further study.

CD4 + T cell differentiation in rheumatoid arthritis / 国际儿科学杂志

The dysfunction of T cells, especially the interaction of antigen presenting cells and CD4 + T cells, leads to abnormal activation of CD4 + T cells and the initiation of adaptive immune response.Dysfunction of the immune system plays an important role in the pathogenesis of rheumatoid arthritis.It is always considered as the central link of synovial continuous inflammation, articular cartilage and bone destruction in rheumatoid arthritis patients.Exploring CD4 + T cell differentiation and cell subsets provides a new perspective for understanding of arthritis and helps to identify new drug targets.

Classification, early screening and treatment of severe combined immunodeficiency disease / 国际儿科学杂志

Severe combined immunodeficiency(SCID)is a kind of severe primary immunodeficiency disease.Patients often develop symptoms after birth, which is characterized by recurrent and life-threatening infection, sometimes accompanied by varying degrees of dysplasia.According to the classification proposed by the PID expert Committee of the International Union of Immunological Societies, SCID is clinically classified by the number of lymphocytes.Early screening and intervention of SCID is significant to improve the prognosis.With the promotion of TREC and other early screening methods, the detection rate of SCID has significantly improved, but the accurate detection rate in different ethnic groups still needs further explored.Hematopoietic stem cell transplantation is a traditional therapy for radical cure of SCID.And the safety of gene therapy for SCID has been gradually guaranteed with continuous improvement during recent years.This article will review the classification, early screening methods and treatment progress of SCID.

Comparison of different treatment regiments in resistant Kawasaki disease / 中华风湿病学杂志

Objective:To investigate the different effects of different treatment regimens in resistant Kawasaki disease (KD) and to provide evidence for clinical treatment.Methods:Forty-nine inpatient children with resistant KD from July 2017 to June 2019 in Children's Hospital of Nanjing Medical University were enrolled into this study. Treatment and follow-up were still in progress. Rank sum test and χ2/Fisher test were used for statisic. Results:The incidence of resistance in infliximab group was significantly lower than that of intravenous immunoglobulin (IVIG) retreated group ( P<0.05). Sixteen cases were treated with 5 mg/kg infliximab (IFX), and 33 cases received methylprednisolone and an additional dose of IVIG. Nine cases who were resistant to IVIG and methylprednisolone were treated with IFX, 6 patients responded to IFX, 3 of them were treated with cyclosporine. Coronary artery changes were followed up. Coronary artery lesions (CALs) were improved in the IFX group, CALs occurred in 12(36%) patients received IVIG and methylprednisolone, 4 of them were improved( χ2=0.633 , P=0.426). Patients were followed up for 3-24 months, the incidence of CALs persistence was statistically significantly different between the two groups (0 vs 24%, P=0.021]. Conclusion:IFX might be an effective and tolerable treatment for resistant KD.

Macrophage activation syndrome: A challenge for pediatrician from rheumatology department and pediatric intensive care unit / 中国小儿急救医学

Macrophage activation syndrome(MAS)is a potentially life-threatening complication of rheumatic disorders.Macrophage activation-like syndrome refers to sepsis patient with dominant pro-inflammatory mechanism of organ dysfunction.Decreased cytolytic function results in prolonged interaction of the effective lymphocytes and their target antigen presenting cells, thus resulting in the pro-inflammatory cytokine storm which lead to multi-organ systerm failure.Early diagnosis remains challenging even there is a set of universal diagnostic criteria.Intravenous pulse methylprednisolon combination with cyclosporin A is still the mainstream therapeutic protocol in domestic.Novel cytokine-targeted approaches are being explored for safer and effective therapies for children with MAS.

Pathogenesis and treatment of the syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis / 国际儿科学杂志

The syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA)is the most common cause of periodic fever in childhood.The diagnosis of PFAPA is typically made on clinical grounds.The patients usually show normal growth and development.The current pharmacological treatment includes corticosteroids for the management of febrile episodes, colchicine for the prophylaxis of febrile episodes, and other medication with unproven efficacy.Tonsillectomy is an option for selected patients.Usually PFAPA syndrome resolves during adolescence, but there is increasing evidence that this condition may persist into adulthood.This article reviews the pathogenesis and treatment of PFAPA in order to raise pediatricians′ awareness of this disease.

Study progress of microbiome in immune diseases / 中华实用儿科临床杂志

Microbiome is a new research field, and it associated with a variety of chronic autoimmune diseases.The microbiome has received increasing attention as a potential contributing factor to the development of a wide array of immune-mediated diseases, including inflammatory bowel disease, type 1 diabetes mellitus and juvenile idiopathic arthritis.Gut microbiota plays a crucial role in modulating innate and acquired immune responses.The microbiome may influence the development of the immune system, the integrity of the intestinal mucosal barrier, and the differentiation of T cell subsets, and finally resulting in autoimmune diseases.The potential to manipulate the microbiome, might then offer perspectives for future therapeutic interventions.Before such interventions can be thought, a deeper understanding of the cause and effect relationship between these immune diseases and the microbiome is needed to first obtain.Now, the advances in the study of microbiome in immune diseases are discussed.

Treatment of systemic juvenile idiopathic arthritis: is the conventional approach converted? / 中华实用儿科临床杂志

Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory disorder characterized by fever,lymphadenopathy,arthritis,rash and serositis.In sJIA,systemic inflammation has been associated with dysregulation of the innate immune system,suggesting that it is an autoinflammatory disorder.Interleukin(IL)-1 and IL-6 play a major role in the pathogenesis of sJIA.Glucocorticoids and disease modifying anti-rheumatic drugs(DMARDS) are the conventional treatment of patients with sJIA.The major advances in the therapy of sJIA are the applications of IL-1 and IL-6 inhibitors and have shown to be highly effective.Recent data suggests that early cytokine blockage might alter the chronic arthritis course,which reflect a potential window of opportunity in the care of children with sJIA.The purpose of this article is to discuss the treatment approach of the patients with sJIA according to the recently published literature.

Successful treatment of refractory systemic'onset juvenile idiopathic arthritis with tocilizumab: a retrospective analysis of 25 cases / 中华风湿病学杂志

Objective To investigate the efficacy and safety of tocilizumab inpatients with refractory systemic'onset juvenile idiopathic arthritis (SoJIA),and to provide a new option for the treatment of this severe disease.Methods We retrospectively studied 25 cases of hospitalized patients with refractory SoJIA treated withtocilizumab,of whom 22 had data that fit for analysis,from May 2005 to February 2016.Data of 22 cases were collected retrospectively from physicians in charge of the patients.Children with SoJIA were treated with nonsteroidal antiinflammatory drugs (NSAIDs),Glucocorticoid (GC),methotrexate,cyclosporin A,etanerceptetc before,but still in high disease activity due to inadequate response were involved.Weretrospective analyzedthe laboratory test results like C'reactive protein (CRP),Erythrocyte sedimentation rate (ESR),Ferritin and other inflammatory index.Improvement of pain,fever,rash,hepatosplenomegaly and lymphadenectasis of active SoJIA (disease course ≥6 months,and inadequate response to NSAIDs and GC) after tocilizumab treatment (Body weight ≥30 kg,8 mg/kg;Body weight＜30 kg,12 mg/kg,per 4 weeks) were analyzed.Safety data of 22 cases were collected throughout the treatment period including neutropenia,infections,anaphylaxis and elevated liver enzymes etc.We also retrospectively analyzedthe dose change of GC and the long'term effect.Dichtomous paramenters were compared teween groups using thex2 test.Continuous parameters were compared using the analysis of uariance.Results In comparison to the indices before the treatment,the level of CRP [(8.7±2.2) mg/L vs (111.6±74.4) mg/L,F=5.192,P=0.002],ESR [(6.4±6.3) mm/1 h) vs (65.6±24.3) mm/1 h,F=50.393,P=0.000],white blood cell (WBC) [(8.4±2.5)×109/L vs (17.6±8.6)×109/L,F=9.321,P=0.000],Neutrophil count [(4.9±2.4)×109/L vs.(14.4±8.7)×109/L,F=10.541,P=0.000],blood platelet (PLT) [(269.5±79.2)×109/L vs (405.4± 145.3)×109/L,F=5.704,P=0.000] and globulin [(19.2±4.1) g/L vs (30.1±3.8) g/L,F=22.896,P=0.000] decreased rapidly and hemoglobin [(118.3±9.0) g/L vs (108.5±9.8) g/L,F=4.693,P=0.002] increased significantly at 24 weeks after Tocilizumab (TCZ) treatment.Clinical manifestationssuch as fever,rash,hepatosplenomegaly,joint swelling and pain were significantly improved.GC dose [(1.25±3.8) mg·kg-1·d-1 vs (16.2±12.8) mg·kg-1·d-1,F=8.21,P=0.000] were significantly reduced after TCZ treatment (P＜0.05);American College of Rheumatology (ACR) Pedi 30/50/70/90 was improved after TCZ treatment.Adverse events occurred in 3 cases of 25 children,who were not included in the statistical analysis group.Conclusion This retrospective case series has demonstrated the efficacy of tocilizumab in SoJIA,low incidence of adverse reactions.Further studies are needed to be developed because this case series haslimited sample size.

Recognition of macrophage activation syndrome / 中华实用儿科临床杂志

Macrophage activation syndrome (MAS)is a serious potentially life -threatening complication seen primarily in patients with systemic onset juvenile idiopathic arthritis (sJIA).Clinical symptoms include persis-tent fever,liver and spleen lymph node enlargement,cytopenia,hyperferritinemia,hypofibrinogenemia,hypertriglyceri-demia,coagulation disorders,and hemophagocytosis can be seen in the bone marrow.This article summarizes the characteristics of MAS occurring in the context of sJIA and discuss the recent advances in classification systems and management.

Arthritis as the initial manifestation in children with tuberculosis:clinical analysis of five cases / 临床儿科杂志

Objective To explore the diagnosis and treatment of five children with tuberculosis with arthritis as the initial manifestation. Methods The clinical features, laboratory tests and imaging manifestation of 5 children with joint tuberculosis were retrospectively analyzed. Results The course of disease was different. All the five patients were males (mean age 8.5 ±2.9 years old) and suffered from articular symptoms as initial feature. Four of them were diagnosed and treated as rheumatoid arthritis by other hospitals for up to three years, two patients have tuberculosis contact history, and another two patients were found with bone destruction, and one patient has pathologic fracture. Conclusions Tuberculosis is easily misdiagnosed as juvenile idiopathic arthritis , which deserves attention from a pediatric rheumatology physician.

Severe hepatic injury for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis / 中华风湿病学杂志

Objective To analyze the clinical features and laboratory data of 10 patients with macrophage activation syndrome (MAS) complicating systemic onset juvenile idiopathic arthritis (soJIA),which were characterized by acute severe liver injury.Methods Data of 10 patients with soJIA/MAS from Nanjing Children's Hospital were collected retrospectively.The clinical features,laboratory findings,treatment,outcomes and prognosis were analyzed.Results In the total 10 patients,female (6/10) outnumbered male.Their age ranged from 1.5 to 9.5 years old (average 5.2±2.6).The most remarkable clinical manifestations were severe liver injury without systemic features,representing as hepatomegaly (10/10),splenomegaly (2/10) and strikingly increased transaminase (10/10,median:ALT 1 445 U/L,AST 885 U/L).Central nervous system dysfunction and hemorrhages were recorded in 20％ of the patients.Two patients had pulmonary infection.Laboratory data showed that platelet count was less than normal or precaution value (10/10,≤262×10g/L).Hyperferritinaemia (10/10,median:17 329 mg/ml) and soluble CD25 elevation (median:3 140 U/ml) were common in the soJIA/MAS patients.Evidence of macrophage hemophagocytosis was found in 90％ of the patients (9/10) who underwent bone marrow aspiration.Pathological findings of liver biopsy from 1 patient revealed massive infiltration of mononuclear cells in the portal tracts.Nearly all patients (9/10) received intravenous pulse methylprednisolone therapy,combined with cyclosporine A and high-dose intravenous immunoglobulin.Eight patients had good outcome.Only 2 patients were complicated with severe interstitial lung disease during 12-months follow-up.Conclusion MAS should be considered when patients with soJIA represents acute severeliver injury without systemic features combined with other laboratory data.Intravenous pulse methylprednisolone and cyclosporine A therapy may improve the prognosis of soJIA/MAS.

Clinical features and long - term follow - up of neonatal lupus erythematosus / 中华实用儿科临床杂志

Objective To investigate the clinical features and long - term prognosis of neonatal lupus erythe-matosus(NLE)and to improve the understanding of NLE. Methods The clinical manifestations and related serologi-cal tests of NLE children diagnosed from June 2010 to January 2014 were analyzed. Regular follow - up was carried out to detect the general condition,rash,blood routine,urine routine,liver and kidney function,complement,red blood cell sedimentation rate(ESR),auto antibodies,electrocardiogram,and ultrasound cardiogram. Results Among the 11 NLE cases,there were 6 male and 5 female patients. All had lesions on skin,3 cases had hematologic changes,7 cases were had liver damage,and 4 cases had heart impairment. The antinuclear antibody and anti - sjogren sydrome A/ Ro antigen (SSA/ Ro)were positive in all the patients. The anti - sjogren sydrome B antigen was positive in 5 patients. The anti -double stands deoxyribonucleic acid antibody was positive in 4 patients. Antibody against U1 - ribonudeoprotein was positive in 3 patients,and the level of ESR was higher in 5 patients. The antinuclear antibody and anti - SSA/ Ro anti-body were positive in all mothers. Only 1 mother had no symptom before pregnancy,7 patients had SLE,3 patients had sjogren syndrome. Seven patients received protect liver enzyme treatment,3 cases of glucocorticoid therapy,and 1 case had combined intravenous treatment with gamma globulin. Among the 11 cases,10 cases were followed up for 10 months to 4 years,while 1 case died from complete bundle branch block after 5 weeks of birth. At 1 year old,10 cases of cuta-neous lupus damage had liver damage were resorted to normal,and the rheumatic autoimmune related autoantibodies of 9 cases turned to be negative,but 1 case was diagnosed as Kawasaki disease when she was 1 year old. Conclusions One of the most common clinical manifestations of NLE was damage of skin,had the liver and blood system abnormity were common but usually not serious. Heart disease especially complete atrioventricular block was less. The long - term follow - up for children with NLE is necessary,and the majority of the prognosis is good,as only a few have the possibi-lity of developing other autoimmune diseases.

Ultrasonic diagnosis and clinical analysis of eosinophilic cystitis in children / 中华实用儿科临床杂志

Objective To explore the ultrasound imaging and the clinical analysis of eosinophilic cystitis in children and to improve the understanding of this very rare clinical disease.Methods The ultrasound imaging of 9 patients who were diagnosed as eosinophilic cystitis in Nanjing Children's Hospital Affiliated to Nanjing Medical University from Jul.2007 to May 2013 were analyzed retrospectively,and the relevant literatures were reviewed.Results The ultrasound imaging of the 9 patients were described as follows:4 cases showed a diffuse thickening bladder wall,2 cases showed a localized mass-like thickening bladder wall,and 3 cases showed a markedly thickening anterior bladder wall and bilateral bladder wall.Laboratory studies showed that all the patients were presented with eosinophilia.Six patients underwent cystoscopy that showed an erythematous,and velvety appearance of the bladder mucosa.Histopathology disclosed a bladder mucosal tissue with dense interstitial eosinophilic infiltration consistent with eosinophilic cystitis.Three patients had clinical resolution under the treatment of anti-infections and urine alkalinization.Other 6 patients received prednisone at 0.5-1.0 mg/kg and an antihistamine treatment.Prednisone was eventually tapered off after 2-week reemission.Regular follow-up by urinary bladder ultrasound and urine routine did not show any disease recurrence in 9 children.Conclusions The combination of bladder wall thickening and peripheral eosinophilia may suggest the likely diagnosis of eosinophilic cystitis.Cystoscopy with bladder biopsy is the most important step in the diagnosis of eosinophilic cystitis.Anti-histamines and corticosteroids can be used as the primary management and have good results.

Comparative analysis of childhood macrophage activation syndrome and other hemophagocytic syndrome / 中华风湿病学杂志

Objective To compare the clinical features, diagnosis, treatment and prognosis between macrophages activation syndrome (MAS) and other hemophagocytic syndrome (HPS). Methods Thirty-six children with HPS were identified at Nanjing Children's Hospital during January 2006 to March 2009. They could be classi-fied into MAS group (13 patients) and other HPS group (23 patients). All relevant clinical features, laboratory data, treatments and outcomes were analyzed with t test,χ2 test and Fisher's exact test.Results Patients with MAS tended to be elder than those with other HPSs [(7.7±1.3) years vs (2.6±0.5)years, t=3.899, P=0.004]. There was no difference in gender distribution. In MAS cases, the central nervous system (69% vs 13%, P=0.001), circulatory system (23% vs 9%, P=0.047) and the urinary system (38% vs 9%, P=0.033) were usually involved. The clinical symptoms of MAS were more sever than other HPS. Serum ferritin [(9703±9819) μg/L vs (4569±1396) μg/L, t=2.854, P=0.015] and erythrocyte sedimentation rate (ESR) [(53±32) mm/1 h vs (20±14) mm/1 h, t=2.708, P=0.020] changed more obviously in MAS cases compared with other HPS. Conclusion, Childhood MAS is different from other HPS in terms of age, etiology, clinical manifestations, laboratory tests and treatments.

Antisense phosphorothioate oligodeoxynucleotide resistance to respiratory syncytial virus infection in vitro / 重庆医科大学学报

Objective:To investigate the antiviral effects of antisense phosphorothioate oligodeoxynucleotide (AODN) in 9HTE infected with respiratory syncytial virus (RSV)in vitro.Methods:In this study,the antisense phosphorothioate oligodeoxynucleotide which complemented to genomic NS1 and M2mRNA of RSV was used to investigate antiviral activity in vitro.The cytopathic effect was observed and the cell survival rates were measured by MTT assay.Results:1.9HTE cell infected with RSV almost all died when the multiplicity of infection(moi)is above 0.1 after 5 days cell culture.2 The antisense phosphorothioate oligodeoxynucleotide could increase the cell survival rates in a dose dependent manner.Conclution:These studies indicate that the genomic NS1 gene and M2mRNA may play an important role in regulating RSV replication and AODN may have inhibitory activity on RSV replication.The results established the basis for further study on new drugs against RSV infection.

CD40L expression on the CD4~+T-cells in children with Kawasaki disease and it’s correlation with coronary artery lesion / 中国免疫学杂志

Objective:To explore the pathogenesis of coronary artery lesions in Kawasaki disease(KD) by detecting expression of CD40L on T-cells from patients with KD.Methods:Blood samples were collected from 26 patients with KD before and after intravenous immunoglobulin(IVIG) treatment. Age-matched febrile 16 children with various diseases were studied in parallel as controls. Age-matched normal control 15 children were studied as controls. CD40L expression on T-cells was detected by flow cytometry, soluble E-selection and soluble CD40L levels were measured by enzyme-linked immunosorbent assay.Results:CD40L expression on CD4+T-cells and soluble E-selection levels were significantly higher in patients with KD than that in the febrile control(FC) group and normal group(P