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Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.
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Objective:To observe the clinical efficacy of intra-articular injection with Triamcinolone acetonide on the treatment of juvenile idiopathic arthritis (JIA).Methods:The clinical data of 26 children diagnosed with JIA undergoing the intra-articular injection of Triamcinolone acetonide for the joints with obvious swelling and pain at the Children′s Hospital Affiliated to Capital Institute of Pediatrics from October 2018 to December 2019 who were retrospectively analyzed.Erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) were tested before and after the application of Triamcinolone acetonide.Detailed clinical manifestations were recorded.The nonparametric Kruskal- Wallis test was used to compare the differences in clinical evaluation indicators and changes in laboratory tests at diffe-rent treatment times. Results:Among the 26 children, 8 were boys and 18 were girls.After the intra-articular injection of Triamcinolone acetonide, 9 cases (34.62%) achieved complete remission, 15 cases(57.69%) achieved partial remission, and 2 cases (7.69%) were not responsive to the intra-articular injection.The overall therapeutic efficacy was 92.31%.Compared with pre-treatment period, from 4 weeks after treatment, assessment of disease activity by the physicians and parents of the children was significantly improved after 4-week treatment, and the number of active joints, ESR and CRP and the Juvenile Arthritis Disease Activity Score with 27 joints (JADAS 27) gradually decreased, and the differences were statistically significant (all P<0.05). No adverse drug reactions were seen during the treatment and follow-up period. Conclusions:Intra-articular injection of Triamcinolone acetonide is effective in contro-lling joint symptoms of JIA with less adverse events.
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Objective:To investigate the clinical characters and prognosis of patients with systemic-onset juvenile idiopathic arthritis associated interstitial lung disease (SoJIA-ILD).Methods:Clinical manifestations, imaging features and prognosis were analyzed in 75 patients with SoJIA between October 2010 and December 2019 in the Second Affiliated Hospital of Wenzhou Medical University.Results:Seventy-five patients with SoJIA were enrolled. Among 12 children with SoJIA-ILD, 6 were male and 6 were female. The mean age of onset was (7.9±2.6) years. All of the 12 patients had fever. Ten patients had arthritis which mainly occurred in large joints. The incidence of arthritis was knee, hip and shoulder from high to low. Two patients had no joint involvement at the onset of the disease and had no joint symptoms during the follow-up. Nine patients (75%) had fever, rash and arthritis at the same time. The clinical features of ILD were mostly nonspecific, including cough in 8 cases (75%), shortness of breath in 7 cases (58%), chest pain in 3 cases (25%), velcro sound in 4 cases (33%) and pulmonary hypertension in 1 case (8%). Inflammatory indicators were all signifi-cantly elevated, among which was CRP (235±112) mg/L, ESR (39±25) mm/1 h, serum ferritin (SF) (1 312±384) ng/ml and serum amyloid A (SAA) (212±101) mg/L. High resolution computed tomography (HRCT) of the chest presented as reticular or line shadows in 12 patients, consolidation in 7 patients, ground interlobular septal thickening in 5 patients, glass opacity in 4 patients and honeycomb lung in 1 patient. ILD occurred in 4 cases (33%) in the early stage of SoJIA (disease course ≤6 months), and 8 cases (67%) in the medium and late stages of the disease course (>6 months), but all appeared in the active status of SoJIA. All of 12 patients received glucocorticoids therapy, 11 patients received high dose of glucocorticoid (>1 mg·kg -1·d -1) and 2 pa-tients received intravenous methylprednisolone pulse therapy. All of 12 patients were treated with glucocorti-coids combined with immunosuppressant or disease modifying antirheumatic drugs and 5 patients needed dual therapy or triple therapy. One case had been treated with biological agents before the occurrence of lung injury and the other 11 cases had not used biological agents before. After the diagnosis of SoJIA complicated with ILD, 4 cases were treated with tocilizumab. Macrophage activation syndrome (MAS) was found in 7 cases and 25% had MAS for two times or more. Ten patients had partial remission or complete remission and 2 patients died of respiratory failure. Conclusion:SoJIA-ILD maybe asymptomatic at the early stage of the disease. It is associated with disease activity of SoJIA. HRCT examination is very important for early diagnosis. Patients with SoJIA-ILD have higher rate of recurrence, death and MAS. It needs to arouse the clinicians' attention.
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Objective:To analyze cytokine pattern of systemic onset juvenile idiopathic arthritis (SOJIA) combined with macrophage activation syndrome (MAS) in children, and study the early diagnostic value in MAS.Methods:The clinical data of 157 children with SOJIA from January 2013 to March 2018 in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. Among them, SOJIA combined with MAS was in 15 cases (SOJIA combined with MAS group), and simple SOJIA was in 142 cases (simple SOJIA group). The peripheral blood levels of interleukin (IL)-2, IL-4, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were measured by flow cytometry cytometric beads array. The characteristics of cytokine pattern was analyzed.Results:The IL-10 and IFN-γ in SOJIA combined with MAS group were significantly higher than those in simple SOJIA group: 40.5 (7.9, 236.9) ng/L vs. 4.1 (2.0, 98.7) ng/L and 55.8 (18.5, 500.0) ng/L vs. 4.4 (1.4, 30.1) ng/L, and there were statistical differences ( P<0.01); there were no statistical difference in IL-2, IL-4, IL-6 and TNF-α between 2 groups (P>0.05). Pearson correlation analysis result showed that IL-10 was positive correlated with IFN-γ in SOJIA children with MAS ( r = 0.638, P = 0.011). Receiver operating characteristic curve analysis result showed that the area under the curve (AUC) of IFN-γ in predicting MAS was 0.991, 95% CI 0.974 to 1.000, the optimal critical value was 18.45 ng/L, the sensitivity was 92.5%, and the specificity was 95.1%; the AUC of IL-10 in predicting MAS was 0.944 (95% CI 0.893 to 0.996), the optimal critical value was 7.75 ng/L, the sensitivity was 91.7%, and the specificity was 81.7%. Conclusions:The significant increased IL-10 and IFN-γ is helpful for the early diagnosis MAS in children with SOJIA.
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Objective To investigate the psychosocial functioning and risk factors of children with juvenile idiopathic arthritis (JIA).Methods A total of 79 children with JIA were selected from the inpatients and outpatients in the department of clinical immunology,a top-grade hospital in Xi'an from February to December,2017.Their demographic and disease data were collected by self-designed questionnaires.Disease remission was confirmed by using the JADAS-27 and pain intensity by visual analogue scale (VAS).The Children's Depression Inventory (CDI) and Multidimensional Anxiety Scale for Children (MASC) were rated by the children themselves.All data were analyzed with SPSS 17.0.Results A total of 316 effective questionnaires were collected,including 79 demographic questionnaires,disease questionnaires,CDI and MASC respectively.(1) The total scores of CDI were 15.22 ± 9.56.The highest scores were found for the subscale of "lack of happiness" (4.57 ± 3.63),while the lowest for the subscale of "low self-esteem" (1.75 ± 1.57).The total scores of MASC were 39.15 ±21.12.The highest scores were found for the subscale of "Injury avoidance" (13.09 ± 5.57) while the lowest for the subscale of "separation anxiety" (7.68 ± 5.66).(2) Multiple stepwise linear regression analysis showed that pain,disease activity,hormonal side effects and fatigue were the main risk factors of the psychosocial functioning of the children with JIA.Conclusions The psychosocial functioning of children with JIA was not satisfied.It suggested that we should not only take the appropriate clinical treatment to control the disease but also take combined therapy such as psychological intervention as early as possible.
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Objective@#By studying the efficacy of interleukin (IL)-6 receptor antagonist (tocilizumab) on acute inflammation of systemin juvenile id-iopathic arthritis (sJIA) and its effect on the downstream signaling pathways and inflammatory factors of IL-6 to further reveal the role of tocilizumab in sJIA.@*Methods@#From December 2015 to December 2018, 64 sJIA children were randomly divided into two groups: 31 cases who were treated with tocilizumab+ glucocorticoid+disease-modifying anti-rheumatic drugs (DMARDs) as the tocilizumab group, 33 cases who were treated with placebo (vitamin C) + glucocorticoid+DMARDs as the control group. They were treated for one year. The levels of IL-2, IL-4, IL-6, IL-10 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of p65 and receptor activator for nuclear factor-κB ligand (RANKL) in peripheral blood mononuclear cells (PBMCs) were detected by quantitative polymerase chain reaction (qPCR). The expressions of signal transducer and activator of transcription (STAT3)/phosphates signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signaling 3 (SOCS3) before and after treatment were detected by Western blotting. The differences between groups were analyzed by variance analysis. Normal distributed data was tested by K-W test. Twenty normal control subjects came from the pediatric clinic in our hospital.@*Results@#There was no significant difference in the demographic data between the two groups (P>0.05). Among them, 2 children who were treated with tocilizumab dropped out after one month treatment and three months due to un-affordability respectively. The C-reactive protein (CRP), ferritin (FER), erythrocyte sedimentation rate (ESR) in the tocilizumab treatment group decreased significantly after 6 months and 1 year when compared with the disease control group. The concentration of IL-6 in the tocilizumab group (77±46) pg/ml, control group (82±40) pg/ml were higher than that in the healthy control group (10±3) pg/ml (F=4.683, P=0.001; F=2.581, P=0.03). After one year, the concentration of IL-6 (316±42) pg/ml in the tocilizumab group was higher than that in the disease control group (62±40) pg/ml (F=11.2, P=0.001). The expression of RANKL and p65 mRNA in treatment group was significantly higher than that in healthy control group (K-W=10.03, P<0.01; K-W=9.42, P<0.01). After one year, the expression of RANKL and p65 mRNA in treatment group was lower than that in disease control group (K-W=9.964, P<0.01; K-W=10.75, P<0.01). The expression of STAT3/p-STAT3/SOCS3 in disease control group before medication was significantly higher than that in healthy control group, while the expression of p-STAT3/SOCS3 in the treatment group was significantly higher than that in healthy control group. The expression of STAT3/p-STAT3 in the tocilizumab group was significantly lower than that in the disease control group (K-W=12.54, P<0.01; K-W=10.52, P<0.01).@*Conclusion@#Tocilizumab can effectively alleviate the symptoms of sJIA in active phase, down-regulate the expression of STAT3/p-STAT3 protein, thereby reducing the transcription of downstream nuclear factor (p65, RANKL) mRNA, thereby affecting the proliferation of synovial cells and reducing bone destruction, but has no significant effect on the secretion of IL-6.
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Objective By studying the efficacy of interleukin (IL)-6 receptor antagonist (tocilizumab) on acute inflammation of systemin juvenile id-iopathic arthritis (sJIA) and its effect on the downstream signaling pathways and inflammatory factors of IL-6 to further reveal the role of tocilizumab in sJIA.Methods From December 2015 to December 2018,64 sJIA children were randomly divided into two groups:31 cases who were treated with tocilizumab+ glucocorticoid+disease-modifying anti-rheumatic drugs (DMARDs) as the tocilizumab group,33 cases who were treated with placebo (vitamin C) + glucocorticoid+DMARDs as the control group.They were treated for one year.The levels of IL-2,IL-4,IL-6,IL-10 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA).The expressions of p65 and receptor activator for nuclear factor-κB ligand (RANKL) in peripheral blood mononuclear cells (PBMCs) were detected by quantitative polymerase chain reaction (qPCR).The expressions of signal transducer and activator of transcription (STAT3)/phosphates signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signaling 3 (SOCS3) before and after treatment were detected by Western blotting.The differences between groups were analyzed by variance analysis.Normal distributed data was tested by K-W test.Twenty normal control subjects came from the pediatric clinic in our hospital.Results There was no significant difference in the demographic data between the two groups (P＞0.05).Among them,2 children who were treated with tocilizumab dropped out after one month treatment and three months due to un-affordability respectively.The C-reactive protein (CRP),ferritin (FER),erythrocyte sedimentation rate (ESR) in the tocilizumab treatment group decreased significantly after 6 months and 1 year when compared with the disease control group.The concentration of IL-6 in the tocilizumab group (77±46) pg/ml,control group (82±40) pg/ml were higher than that in the healthy control group (10±3) pg/ml (F=4.683,P=0.001;F=2.581,P=0.03).After one year,the concentration of IL-6 (316±42) pg/ml in the tocilizumab group was higher than that in the disease control group (62±40) pg/ml (F=11.2,P=0.001).The expression of RANKL and p65 mRNA in treatment group was significantly higher than that in healthy control group (K-W=10.03,P＜0.01;K-W=9.42,P＜0.01).After one year,the expression of RANKL and p65 mRNA in treatment group was lower than that in disease control group (K-W=9.964,P＜0.01;K-W=10.75,P＜0.01).The expression of STAT3/p-STAT3/SOCS3 in disease control group before medication was significantly higher than that in healthy control group,while the expression of p-STAT3/SOCS3 in the treatment group was significantly higher than that in healthy control group.The expression of STAT3/p-STAT3 in the tocilizumab group was significantly lower than that in the disease control group (K-W=12.54,P＜0.01;K-W=10.52,P＜0.01).Conclusion Tocilizumab can effectively alleviate the symptoms of sJIA in active phase,down-regulate the expression of STAT3/p-STAT3 protein,thereby reducing the transcription of downstream nuclear factor (p65,RANKL) mRNA,thereby affecting the proliferation of synovial cells and reducing bone destruction,but has no significant effect on the secretion of IL-6.
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Objetivo: Avaliar a massa óssea e a composição corporal em adultos com história de ARJ. Métodos: Estudo caso-controle em 6 pacientes adultos com ARJ e 24 controles com mesmo perfil demográfico. Resultados: Peso e o IMC foram maiores nos pacientes com ARJ. Todos os parâmetros da composição corporal foram diferentes. Pacientes com ARJ apresentaram maior taxa de gordura corporal e menor porcentagem de massa magra apesar de possuírem peso e IMC maiores. A baixa massa óssea foi observada em dois pacientes com ARJ (33,3%) e em nenhum controle (0%) (Teste Exato de Fisher p=0,034). Embora a DMO média de todos os sites esqueléticos avaliados tenha sido menor no grupo JRA, não houve diferença estatística. Três pacientes com JRA (50,0%) usaram prednisona até a idade adulta com uma dose cumulativa média de 14,600 mg (± 9341,4 DP). Conclusões: Pacientes adultos com JRA ativo apresentaram maior frequência de baixa massa óssea e composição corporal diferente em relação ao grupo controle. Eles apresentaram mais massa gorda e menos massa magra.
Objective: To evaluate bone mass and body composition in adults with a history of JRA. Methods: A case-control study in 6 adult patients with JRA and 24 controls with same demographic profile. Results: Weight and BMI were higher in patients with JRA. All body composition parameters were different. JRA patients showed higher percentage of body fat mass and lower lean mass despite having higher weight and BMI. Low bone mass was observed in two patients with JRA (33.3%) and was not present in control group (0%) (Fisher's exact test p = 0.034). Although mean BMD of all evaluated skeletal sites was lower in JRA group there was no statistically difference. Three JRA patients (50.0%) used prednisone until adulthood with mean cumulative dose of 14,600 mg (± 9341.4 DP). Conclusions: Adult patients with active JRA showed higher frequency of low bone mass and different body composition in relation to control group. They presented more fat mass and less lean mass.
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Objective In 2016,European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)/Pediatric rheumatology international trials organization (PRINTO) released the classification criteria for macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).Due to the similarities of both clinical manifestations and pathogenesis between adult-onset Still dsease (AOSD) and sJIA,we hope to evaluate the 2016 sJIA-AMS classification in AOSD patients.Methods A total of 169 AOSD patients who were hospitalized in Renji Hospital were enrolled in this study.AOSD patients were divided into AOSD with MAS and AOSD without MAS,using the 2016 sJIA-MAS criteria.The data of the two groups were analyzed by Chi-square test,Mann-Whitney U test and binary Logistic analysis,and factors influencing the prognosis of patients were analyzed by Kaplan-Meier and COX regression analysis.Results According to sJIA-MAS criteria,56 AOSD patients with MAS were identified in all the 169 AOSD cases.In AOSD patients,the incidence of splenomegaly and pericarditis/myocarditis was significantly higher in patients with MAS than in AOSD without MAS [42.9％ vs 14.2％,OR(95％CI)=4.50(2.13,9.51),P＜0.01;10.7％ vs 0.9％,OR(95％CI)=13.21 (1.56,113.57),P＜0.01],also the incidence of liver dysfunction was higher in AOSD with MAS [67.8％ vs 11.5％,OR(95％CI)=0.18(7.26,36.33),P＜0.01].Among the AOSD with MAS,62.5％(35/56) of these patients received large-dose glucocorticoid therapy,5.4％ (3/56) received the glucocorticoid pulse therapy,48.2％(27/56) were treated with IVIG,and 26.8％(15/56) were treated with calcium phosphatase inhibitors.The mortality rates of AOSD with MAS was 8.9％(5/56),which was significantly higher than 1.8％(2/113) (OR =5.44,P＜0.05),the mortality rate of the AOSD without MAS.Patients who fulfilled the sJIA-MAS criteria suggested poor prognosis (OR=0.041,P=5.44),and the platelet count ≤ 181× 109/L (OR=12.17,P=0.002),alanine aminotransferase ＞48 U/L (OR=9.43,P=9.040) were also highly suggestive of poor prognosis.Conclusion The 2016 sJIA-MAS classification criteria are particularly valuable for early recognization of MAS in AOSD patients,and convenient to use.AOSD patients fulfilled sJIA-MAS criteria are more severe,and require larger doses of glucocorticoid and more immunosuppression therapy compared to patients without MAS,and the prognosis of these patients is also poor.
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Objective To compare the positive rate of anti-mutant citrulline vimentin (MCV) antibody and anti-cyclic citrullinated peptide (CCP) antibody in serum of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA).To investigate the diagnostic value and significance of anti-MCV and antiCCP antibody in these two diseases.Methods Anti-CCP and anti-MCV antibodies were detected by enzymelinked immunosorbent assay (ELISA).The serum samples were from 113 patients with JIA,632 patients with RA,102 adult without RA and 56 children without RA.Chi-square test and multiple comparisons were used for statistical analysis.Results ① In RA patients,the sensitivity,specificity and area under the receiver operating characteristic curve (ROC curve) of anti-MCV antibody was 90.2％,91.2％,0.919;the sensitivity,specificity and area under the ROC curve of anti-CCP antibody was 92.6％,93.1％ and 0.934.In JIA,the specificity of antibodies was 98.2％,the sensitivity was low.Area under the ROC curve of anti-MCV antibody was 0.579.Area under the ROC curve of anti-CCP antibody was 0.561.② The positive rate of anti-MCV antibody in RA was 90.2％,which was higher than that of JIA (16.8％) (P＜0.01).The positive rate of anti-CCP antibody in RA was 92.2％,which was higher than that of JIA (14.2％) (P＜0.01).The positive rates of antiMCV antibody in JIA with RF-negative polyarthrosis,RF-positive polyarthrosis,systemic type,oligo-joint type,attachment points,unclassified was 11.8％,69.2％,14.3％,17.4％,3.6％,0.The positive rate of anti-CCP was 11.8％,61.5％,14.3％,13.0％,0 and 0 prespectively.For anti-MCV antibody,the chi-square values in patients with RA between RF-negative polyarthrosis,RF-positive olyarthrosis,systemic type,oligo-joint type,attachment points,unclassified arthritis were 160.2,4.02,34.4,102.0,165.1 and 57.0 respectively.There were significant differences between RA and all types of JIA (P＜0.05).The positive rate of anti-CCP antibody in patients with RA between RF-negative polyarthrosis,RF-positive polyarthrosis,systemic type,iligo-joint type,attachment points,unclassified arthritis were 192.3,11.9,44.0,139.4,212.5 and 71.9.There were significant differences between RA and all types of JIA (P＜0.05).Conclusion The diagnostic value of anti-MCV and anti-CCP antibodies is high in RA.Anti-MCV and anti-CCP antibody have certain diagnostic value of JIA.The positive rates of anti-MCV and anti-CCP antibody in the types in JIA are lower than those of RA patients.
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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.
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Objective@#To evaluate the efficacy and side effects of tocilizumab for the treatment of systemic juvenile idiopathic arthritis.@*Method@#In this prospective self case-control study, the children diagnosed with refractory systemic juvenile idiopathic arthritis admitted to Department of Rheumatism and Immunology of Children's Hospital Affiliated to Capital Institute of Pediatrics from December 2013 to June 2016 were enrolled and information before and after treatment of tocilizumab was analyzed. The tocilizumab was introvenously guttae in a dose of 8-12 mg/kg every 2 weeks. Complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested before and after the application of tocilizumab. Detailed clinical manifestations were recorded. All results were analyzed by χ2 test and t test.@*Result@#Forty patients with a median age of (6.6±3.7) years were enrolled, including 15 males and 25 females. All of the patients presented with fever and 38 patients got normal temperature 24-48 hours after treatment with tocilizumab. Symptoms disappeared in 13 and improved in 4 patients after treatment among the 17 patients who presented with arthritis. Within the 10 patients who manifested with rashes, 9 patients' rashes disappeared without relapse accompanied by the normalization of temperature after the treatment of tocilizumab. One patient got normal temperature but intermittently emerged rashes after symptoms of arthritis improved. In the 40 patients, 38 well tolerated tocilizumab while 2 showed rashes and chill which disappeared shortly after antianaphylaxis treatment. No severe treatment-related infection was found in any patients. According to the study, the white blood cell counts(×109/L), CRP(mg/L) and ESR(mm/1h) tested 2 weeks after the treatment with tocilizumab were significantly lower than that before treatment(12.1±1.2 vs. 16.5±1.8, 47±8 vs. 67±9, 21±5 vs. 57±6, t=2.75, 3.98, 5.22, P=0.009, 0, 0, respectively). No significant changes were found in concentration of IL-6 and TNF-α (65(207) vs. 45(137) ng/L, and 14(6) vs. 17(19)ng/L, Z=-1.247 and-1.285, P=0.212 and 0.199 respectively).@*Conclusion@#Tocilizumab is a treatment with good efficacy and safety for refractory systemic juvenile idiopathic arthritis. Adverse effects would be found in some patients.
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Objective To explore the expression of inflammasomes (NLRP3,NLRP12) and related signal proteins in the peripheral blood mononuclear cells (PBMCs) of patients with juvenile idiopathic arthritis (JIA).Methods Samples of children with definite diagnosis of active JIA in Guangzhou Women and Childrens' Medical Center were collected retrospectively.Fifty-five cases were included,among whom 30 were systemic type and 25 were joint type.Blood samples of 22 healthy controls were collected at the same time.Peripheral blood single nuclear cell (PBMCs) were separated and DNA were extracted and reverse transcription (RT) to cDNA.Fluorescent quantitative polymerase chain reaction (PCR) was used to detect NLRP3,NLRP12,ASC,and capase-1 in groups and the difference in their expression between groups were analyzed.Enzyme linked immunosorbent assay (ELISA) was utilized to test plasma levels of interleukin (IL)-6 IL-1,IL-4,IL-10,and their correlation were analyzed.Results The expression of NLRP3,NLRP12,ASC,Capase-1 in the case group (general-group and joint-group) were higher than those in the control group (P＜0.05),but there was no significant difference in the expression levels between groups (P＞0.05).The IL-1 concentration of the case group (body-type group,joint-group) was higher than the control group (P=0.001,U=l) (P=0.001,U=14),however,the level of IL-4 of the case group (body-type group,joint-group) was not significantly different from the control group (U=662,P=0.13) (U=823,P=0.535),IL-I0 of the systemic group was higher than that of the control group (U=750,P=0.023),while there was no difference between groups (U=672,P=0.212).There were no significant difference in the levels of IL-1 (U=658,P=0.408),IL-4 (U=475,P=0.068),IL-10 (U=475,P=0.195) between groups.The NLRP3 mRNA relative expression levels of the case group and the ASC (r=0.44,P=0.013 4) was significant,in addition,IL-1 (P=0.001,R=0.58),erythrocyte sedimentation rate (ESR) (r=0.415,P=0.039),C reactive protein (CRP) (r=0.438,P=0.046) were positively correlated with NLRP12 relative mRNA expression level and ASC (r=0.583 7,P=0.007),CRP (r=0.46,P=0.031 6),ESR (r=0.003,P=0.56),CD8+ T (r=0.414,P=0.036).Conclusion The abnormal expression of JIA inflammasomes in peripheral blood mononuclear cells (NLRP3,NLRP12) may be associated with juvenile idiopathic arthritis.
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Objective To explore the expression of miR-21 and miR-19a in juvenile idiopathic arthritis (JIA) and the relationship among the key target genes (SOCS3,STAT3) in JAK/STAT pathways.Methods The venous blood from 33 cases of active JIA in Guangzhou Women and Children Medical Center were collected.All cases were divided into two groups:the systemic group (n=20),polyarthritis group (n=13).Twenty subjects were used as the normal control group.Peripheral blood mononuclear cells (PBMCs) were extracted and separated with Ficoll.miRNA was extracted and purified and real-time quantitative polymerase chain reaction (RT-PCR) was used to obtain cDNA.Target genes of miRNA were detected through Targetscan and RNA22.U6 was used for reference of miR-19a,miR-21 and β-actin were used for STAT3,SOCS3,IL-6,TNF-α mRNA.All the expression were detected by fluorescence quantitative PCR among the groups and calculated the result in standardized 2-ΔΔCT value,non-parametric test was used to test the differences.Results The expression of miR-21 were significantly reduced in the case group than the control group (Z=2.11,P=0.036),in which miR-21 was 7(7-8.5) times reduced than the SJIA group,6.49 (6-7) times than the pJIA group,the difference was statistically significant (Z=2.615,P=0.014 9;Z=2.654,P=0.0291).But no significant difference of miR-21 expression could be found between the SJIA and PJIA groups (Z=0.221,P =0.827 1).The expression of miR-19a was significantly reduced in the case group than the control group (Z=2.41,P=0.014),in which miR-19a was 11.3 (10-12.1) times to the SJIA group,12.2 (12-13.5) times to the pJIA group,the difference was statistically significant (Z=2.334,P=0.015 7;Z=2.414,P=0.026 6).But no significant difference could be detected in the miR-21 expression between the SJIA and the PJIA groups (Z=0.538,P=0.596).Software estimated that STAT3,SOCS3,TNF-α were the target genes of miR-21 and miR-19a in the JAK/STAT pathways respectively.Fluorescence quantitative PCR had shown that mRNA expression of STAT3 [6.24(2.81,7.54) and 3.97(1.81,5.75),P=0.001,0.008],TNF-α [3.03(2.07,3.80) and 3.42(2.46,4.68),P=0.002,0.001],IL-6[4.75(3.59,6.32) and 3.52(2.31,7.51),P=0.006,0.036],SOCS3[2.54(1.77,4.00) and 3.57(1.95,3.83),P=0.003,0.001] was higher in the case Group (SJIA group,the PJIA group) than the control group;STAT3 mRNA expression was negatively correlated with the miR-21 (r=-0.585 4,P=0.006 7;r=-0.613 4,P=0.044 7) and there was statistically significant difference.TNF-α,SOCS3 mRNA expression in the case group (SJIA group,PJIA group) was negatively correlated with the miR-19a.TNF-α (r=-0.664 2,P=0.001 4),SOCS3 (r=-0.790 3,P=0.000 1) of the SJIA group,was higher than those of the PJIA group TNF-α (r=-0.626 1,P=0.039 3),SOCS3 (r=-0.8824,P=0.003),the difference was significant.Conclusion The expression of miR-21,miR-19a in PBMC in the JIA patients are lower than the control group.The high expression of the target genes,miR-21,miR-19a of STAT3,SOCS3,TNF-α suggest that these genes might associate with,activating of JAK/STAT pathway.
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Objective To semi-quantitatively assess the MRI manifestations of knee in patients with juvenile idiopathic arthritis (JIA) and to explore the relationship between the semi-quantitative scores with clinical inflammatory biomarkers. Methods Fifty children diagnosed as JIA and presented with knee pain, swelling or limitation were enrolled and their clinical and imaging findings were retrospectively analyzed. Contrast-enhanced MRI scan of the knee were performed in all cases (a total of 50 knees). MRI abnormalities, including synovial hypertrophy, joint effusion, bone marrow edema, joint cartilage injury and bone erosion, were assessed with a semi-quantitative score system. The erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) at the same period with MRI were collected. The relationships between the MRI scores and laboratory biomarkers (CRP and ESR) were analyzed with Spearman correlation analysis. Results In MR images of all the 50 knees with JIA, synovial hypertrophy(43, 86%)and joint effusion(40, 80%)were major abnormalities, bone marrow edema was seen in 6 knees, joint cartilage injury in 12 knees and no bone erosion was seen. The scores of synovial hypertrophy, joint effusion, marrow edema, joint cartilage injury and bone erosion were 7(0-12), 3(0-7), 0(0-6), 0(0-10), 0, respectively. There was significant correlation between synovial hypertrophy and joint effusion(r=0.719, P=0.001). There were positive relationship between synovial hypertrophy and ESR and CRP(r=0.306 and 0.285; P=0.031 and 0.043, respectively).Other indexes had no significant relationship with ESR or CRP. Conclusions MRI could comprehensively evaluate knee involvement in patients with JIA. Joint effusion could be a useful reference to evaluate the condition of synovitis for pediatric patients with non-enhanced MR images.
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Introducción: La artritis idiopática juvenil (AIJ) es un grupo heterogéneo de trastornos inflamatorios que se expresan con inflamación, dolor e impotencia funcional en una o más articulaciones en niños menores de 16 años. Las características clínicas y epidemiológicas planteadas por la literatura nacional e internacional son diversas. Objetivos: Describir las características clínicas de los pacientes con diagnóstico de AIJ, subtipos de clasificación, articulación más afectada, relación con género y edad promedio de incorporación al Instituto Teletón Santiago. Pacientes y Método: Estudio descriptivo, transversal. Se identificaron 217 pacientes en cubo OLAP con diagnóstico de AIJ, de éstos se revisaron 174 fichas clínicas (80,1 por ciento) de pacientes activos, con edades entre 7 y 18 años, que fueron atendidos en el Instituto Teletón Santiago durante los años 2012-2013. Los datos se procesaron mediante SPSS versión 17.0. Se calcularon medidas de resumen y la relación entre variables se estableció mediante test de asociación, con p < 0,05. Resultados: Según subtipo de artritis, las mayores frecuencias correspondieron a oligoarticular (31 por ciento) y poliarticular (22,4 por ciento). Las articulaciones más afectadas fueron rodilla (70 por ciento), tobillo (57,6 por ciento) y muñeca (45,9 por ciento). Un 70,1 por ciento del total de pacientes correspondieron al género femenino. Se verifica asociación al género femenino estadísticamente significativa (p = 0,002) en los subtipos poliarticular (razón femenino/masculino = 5,50), oligoarticular (razón femenino/masculino= 3,15) y sistémica (razón femenino/masculino = 1,83). La edad de incorporación al Instituto se registró en promedio a los 9,22 +/- 3,96 años. Conclusión: Las características clínicas generales, tuvieron similitud a lo descrito en literatura, sin embargo, sería conveniente realizar estudios posteriores a nivel nacional.
Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory disorders, which manifest themselves with swelling, pain and loss of function in one or more joints, in children under 16 years of age. Clinical and epidemiological characteristics raised by the national and international literature are varied. Objectives: To describe the general clinical characteristics of patients diagnosed with JIA, regarding subtype classifications, most affected joint, gender and average age of admission at Instituto Teletón Santiago. Patients and Method: A descriptive cross-sectional study with 217 patients diagnosed with JIA identified through OLAP Cubes, was performed. Medical records for 174 (80.1 percent) active patients were reviewed, whose ages ranged from 7 to 18 years of age, and who were treated at the Instituto Teletón Santiago, between the years 2012- 2013. Data was processed using SPSS version 17.0. Summary measures and the association between variables were calculated using c2 Test of Association, with p < 0.05. Results: According to subtype of arthritis, olygoarticular obtained the higher frequencies (31 percent) and polyarticular (22.4 percent). The most commonly affected joints were, knee (70 percent), ankle (57.6 percent) and wrist (45.9 percent). A 70.1 percent of all patients, were female. Association to the female gender was statistically significant (p = 0.002) for the polyarticular subtypes (reason female/male = 5.50), oligoarticular (reason female/male = 3.15 ) and systemic (right female/male = 1.83). The age for admission to the Institute, was recorded at an average of 9.22 +/- 3.96 years. Conclusion: The general clinical characteristics of the population, were similar to those described in literature, however further studies would be useful at the national level.
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Humans , Male , Adolescent , Female , Child , Arthritis, Juvenile/epidemiology , Age Distribution , Chile , Cross-Sectional StudiesABSTRACT
Objective To analyze the changes of celluar and humoral immunity in children with juvenile idiopathic arthritis(JIA),as well as the changes in different subtypes,and to investigate the role of cellular and humoral immunity in the pathogenesis of JIA.Methods Ninety-two JIA subjects and 82 controls(healthy children) were included into this study.The levels of T lymphocyte subsets,natural killer (NK)cells,and B cells were analyzed by using flow cytometry.The serum interleukin-1 (IL-1),tumor necrosis factor-α (TNF-α),interleukin-l0 (IL-10),transforming growth factor-β(TGF-β) levels were detected by using enzyme-linked imnmunosorbent assay (ELISA).The serum IgG,IgM,IgA and C3,C4 levels were detected by using velocity scatter turbidimetry.Independent t-test,One-Way ANOVA test and Pearson analysis were adopted for data analysis.Results 1.In the group of JIA,the levels of CD3,CD4,IL-1,TNF-α,IgG,IgM,IgA and C3 were higher than those in the control group(all P ＜ 0.05),while the levels of CD4CD25,CD8,NK cells,IL-10 and TGF-β were lower than those in the control group(all P ＜0.05),and the ratio of CD4/CD8 was higher than that in the control group (P ＜ 0.05).2.In the group of systemic-onset JIA (so-JIA),the levels of CD4,IL-1,TGF-β,IgG,IgM,IgA,C3 and the ratio of CD4/CD8 were higher than those in the oligoarthritis JIA group(all P ＜ 0.05),while the levels of CD4CD25,CD8,IL-10 were lower than those in the oligoarthritis JIA group(all P ＜ 0.05).In the group of polyarthritis JIA,the levels of IL-1,TNF-α,IgG,IgM and IgA were higher than those in the oligoarthritis JIA group(all P ＜0.05),while the levels of CD4CD25,CD8,IL-10 were lower than those in the oligoarthritis JIA group (all P ＜ 0.05) ; In the group of so-JIA,the levels of CD4,TGF-β,C3 and C4 were higher than those in the polyarthritis JIA group (all P ＜ 0.05).3.The value of IL-1,TNF-α were positively correlated with that of C-reactive protein (CRP),erythrocyte sedimentation rate(ESR) in the JIA group(all P ＜ 0.05),while the value of IL-10,TGF-β was negatively correlated with that of CRP,ESR(all P ＜ 0.05).Conclusions There are cellular immunity and humoral immunity disorders in the JIA.Cellular immunity and humoral immunity are all involved in the pathogenesis of JIA.T helper cells are activated and Th1 cytokines increase,suppressive T cells,regulatory T cells impairment and suppressive cytokines decrease but immunoglobin increase,which involve in auto inflammation reaction and articular destruction in JIA.The immunity disturbances are more striking in so-JIA and polyarthritis JIA.IL-1,TNF-α,IL-10 and TGF-β are correlated with the disease activity.
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Objective To explore the effect of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein injection (rhTNFR:FC) on the expression of cartilage oligomeric matrix protein (COMP) in the synovial fluid and peripheral blood of juvenile idiopathic arthritis (JIA); and to explore the clinical significance of COMP for JIA and the relationship between rhTNFR:FC and COMP in JIA.Methods Thirty-five patients with JIA (JIA group),30 patients with traumatic arthritis (trauma group) and 30 patients with indirect inguinal hernia hernioplasty (normal group) were included.Peripheral blood from all enrolled patients and synovial fluid from 15 JIA and 10 trauma arthritis were obtained for COMP detection before the treatment.Fifteen JIA (group A) patients were treated with combined rhTNFR:FC,diseasemodifying antirheumatic drugs (DMARDs) and non-steroid anti-inflammatory drugs (NSAIDs),20 JIA (group B) were treated with combined DMARDs and NSAIDs.After three to six months' treatment and when the disease were in remission,peripheral blood from group A and B were drawn for COMP detection.In group A,the synovial fluid from 5 patients were obtained for COMP detection after treatment.At the same time,such as tender joint count (TJC),swollen joint count (SJC),time for morning stiffness,blood routine,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and other parameters before and after treatment were measured.The level of COMP was tested by double antibody sandwich enzyme-linked immunosorbent assay.The measurement data were tested for variance and independent sample t-test; and the enumeration data were tested by chi-squared or Fisher's exact test.Pearson's correlation analysis was adopted to analyze the association among the variables.Results ① The blood COMP level before treatment was (0.77±0.29) ng/ml in the JIA group,(1.00±0.28) ng/ml in the traumatic arthritis group,and (1.33±0.37) ng/ml in the normal control group.The level in the former two groups was obviously lower than that in the normal control group.The variation was statistically significant (F=25.345,P＜0.05).The comparison between any two groups was statistically significant (P＜0.05).② The COMP level in the synovial fluid before treatment were (14.8±1.6) ng/ml in the JIA group,(15.1±1.0) ng/ml in the traumatic arthritis group.The variation was not stati-stically significant (t=0.523,P=0.606).③ The serum COMP level of the systemic JIA group was obviously lower than that of the oligoarticular JIA patients,and patients with enthesitis-related arthritis and polyarticular JIA (0.26± 0.03 vs.0.87±0.17,0.89±0.22 and 0.70±0.35 ng/ml,respectively; F=9.244,P＜0.05).④ The serum COMP level of JIA at the acute phase was negatively correlated with white blood cells count (WBC),CRP and ESR (r=-0.556,-0.582 and-0.684,respectively; P all＜0.05).By contrast,no correlation was detected between the serum COMP level and joint tenderness index,joint swelling index,morning stiffness duration,hemoglobin level and platelet count(r=0.06,-0.206,-0.107,0.15 and-0.185,respectively; P all ＞0.05).⑤ The serum COMP level was obviously lower in the JIA with joint destruction than that without joint destruction (0.52±0.22 vs.0.92±0.22 ng/ml; t=5.207,P＜0.05).⑥After treatment,the blood COMP level in group A was (1.33±0.21) ng/ml and (0.96±0.22) ng/ml in group B,which was obviously higher than that in the JIA group before treatment (0.77±0.29) ng/ml.In addition,the level in group A was higher than that in group B.The variation was statistically significant (F=24.681,P＜0.05).⑦ After treatment,the COMP level in the synovial fluid (18.4± 1.1) ng/ml (n=5) was higher than that before the treatment was (14.8± 1.6) ng/ml (n =15).The variation was of statistical significant (t=4.565,P＜0.05).Conclusion The COMP level in blood and synovial fluid declines before treatment and increases after treatment.The increase is more obvious after combined with rhTNFR:FC treatment.The serum COMP level is remarkably decreased in JIA at the acute phase,systemic JIA,and the JIA with destruction of joint,and showes a negative correlation with WBC,CRP and ESR.Serum COMP may be a useful marker of active disease,destruction of joint and growth inhibition for patients with JIA.rhTNFR:FC treatment for JIA can facilitate the recovery of COMP.
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Objective To explore the influence of allergic rhinitis (AR) on patients with systemic onset juvenile idiopathic arthritis (SoJIA).Methods The study involved 44 cases with SoJIA from Department of Pediatrics,Renji Hospital affiliated to School of Medicine of Shanghai Jiaotong University from July 2008 to November 2013.The Clinical and laboratory data of all patients were recorded respectively.This was a retrospective cohort study.According to the diagnosis of allergic rhinitis (AR),children were subdivided into AR group (16 cases) and Non-AR group (28 cases).ACR Pediatric criteria (ACR Pedi) 30/ 50/70 and related indicators of SoJIA between the two groups were compared.In the AR group,the correlation between AR scores and DAS28 was analyzed.When SoJIA of the two groups relapsed,the AR group (the treatment group) received anti-rheumatism for arthritis as well as nasal spray and oral antihistamines for AR.The non-AR group (control group) only received the anti-rheumatism for arthritis.The improvement of SoJIA between the two groups was analyzed.The continuous variables were analyzed by Student's t-test or the MannWhitney U-test as appropriate.Categorical data were compared between different groups by the Chi-square test.Correlations were determined by Pearson or Spearman's ranking.Results ① In the retrospective analysis:the physician's and patients'/parents' general assessment on a 10 cm visual-analogue scale (VAS),number of joints with res-triction of movement,number of swollen joints,ESR,serum ferritin(SF) and childhood health assessment questionnaire (CHAQ) score were significantly elevated in the AR group compared with Non-AR group at the disease onset [(6.7±1.0) cm vs (4.8±1.9) cm; (6.5±1.4) cm vs (3.2±1.5) cm; 4.1±2.7 vs 2.7± 1.7; 3.4±2.4 vs 1.4±1.5; (87±35) mm/1 h vs (61±40) mm/1 h; (888±1 043) μg/L vs (311±324) μg/L; 1.6±0.5 vs 0.7±0.3,respectively; all P＜0.05].At the 3 and 6 months follow-up after disease onset,the proportion of patients who reached ACR pedi 50,70 in AR group were lower than the Non-AR group,while the cumulative glucocorticoid dose was higher in the AR group than that of those without AR [at 3 months 38％ vs 71％; 13％ vs 46％; (76±35) mg/kg vs (43±36) mg/kg,respectively; at 6 months 25％ vs 71％; 19％ vs 64％; 127±57 vs 67±58,respectively,all P＜0.05]; In the AR group,at the disease onset,3 and 6 months follow-up after disease onset,the scores of AR was positively correlated with DAS28(r=0.741,0.703,0.680,respectively; all P＜0.05).② In the prospective study:when SoJIA was relapsed,systemic feature score,the physician's and patients' /parents' general assessment on a l0 cm VAS,number of joints with restriction of movement,number of swollen joints,ESR,SF and CHAQ score were significantly elevated in the treatment group compared with the control group [3.8±1.5 vs 2.1±1.1; (5.6±1.5) cm vs (4.5±1.6) cm; (4.6±1.9) cm vs (3.1±1.5)cm; 3.9±1.9 vs 2.5±1.4; 2.4±0.9 vs 1.5±1.2; 92±27 vs 53±37; 565(339,1 192) μg/L vs 171(85,284) μg/L; 13(0.8,1.6) vs 0.7(0.5,1); respectively; P＜0.05].The improvement rate of the physician's and patients'/parents' general assessment on a 10 cm VAS,number of swollen joints,number of joints with restriction of movement,ESR and CHAQ score at the follow-up 3 months were higher in treatment group than the control group [71(55,86)％ vs 46(0,75)％; 67(45,81)％ vs 28(-4,62)％; 92(77,96)％ vs 70(27,88)％; 65(48,81)％ vs 0(-17,67)％; 100(46,100)％ vs 42(0,100)％; 67(49,85)％ vs 37(0,75)％; P＜0.05].At the follow-up 6 months,the improvement rate of ESR,patients'/ parents' general assessment on a 10 cm VAS,number of joints with restriction of movement and CHAQ score were higher than control group [94(85,96)％ vs 73(33,85)％; 89(65,99)％ vs 63(5,85)％; 100(100,100)％ vs 100(0,100)％; 91(69,100)％ vs 72(11,91)％; respectively,P＜0.05].Conclusion AR may exert an adverse influence on SoJIA.SoJIA patients who are treated with combined with AR may have better outcome than those who are only treated for arthritis.