Clinical analysis of systemic onset juvenile idiopathic arthritis complicated with interstitial lung disease / 中华风湿病学杂志

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.

Significance of cytokine imbalance in systemic onset juvenile idiopathic arthritis combined with macrophage activation syndrome / 中国医师进修杂志

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.

The efficacy of tocilizumab treatment for one year and its effect on the Janus kinase/signal transducer and activator of transcription signaling pathway in systemic juvenile idiopathic arthritis patients / 中华风湿病学杂志

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.

The efficacy of tocilizumab treatment for one year and its effect on the Janus kinase/signal transducer and activator of transcription signaling pathway in systemic juvenile idiopathic arthritis patients / 中华风湿病学杂志

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.

Application of the 2016 European League Against Rheumatism/American College of Rheumatology/Pediatric Rheumatology International Trials Organization classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis in adult-onset Still disease / 中华风湿病学杂志

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.

Comparison of anti-mutated citrullinated vimentin antibodies and anti-cyclic citrullinated peptide antibodies in the diagnosis of juvenile idiopathic arthritis and rheumatoid arthritis / 中华风湿病学杂志

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.

Analysis on the inflammasomes (NLRP3, NLRP12) expression in peripheral blood mononuclear cells in patients with juvenile idiopathic arthritis / 中华风湿病学杂志

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.

Tocilizumab for refractory systemic juvenile idiopathic arthritis / 中华儿科杂志

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.

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.

The expression level and value of miR-21,miR-19a and JAK/STAT pathway in peripheral monocytes of juvenile idiopathic arthritis / 中华风湿病学杂志

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.

MRI manifestation of the knee in juvenile idiopathic arthritis and clinical relevance / 中华放射学杂志

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.

The analysis of PRF1 STX11 UNC13D STXBP2 gene and clinical features in macrophage activation syndrome associated with systemic juvenile idiopathic arthritis / 中华风湿病学杂志

Objective To investigate the clinical characteristics of 34 systemic onset juvenile idiopathic arthritis (SoJIA) complicated with macrophage activation syndrome (MAS) and analyzed the gene PRF1,UNC13D,STX11,STXBP2 to figure out the genetic pathogenesis mechanism.Methods The clinical characteristics of 34 SoJIA complicated with MAS were analyzed retrospectively and coding sequences of PRF1,UNC13D,STX11 were amplified and tested.The Chi-square test was applied to compare the distribution of alleles and genotypes frequencies between SLE patients and healthy controls.Statistical significance was defined as P value ＜0.05.Results A total number of 34 SoJIA complicated with MAS were included.Boys accounted for 69％(23/34),and the median age was 6 years.85％(29/34) cases had genetic tests and four SNPS loci were detected:PRF1 c.1061 C＞T (rs885822); UNC13D c.659 C＞T (rs3744007); STXBP2 c.1483 T＞cC (rs10001) and STXBP2 c.1616 A＞G (rs6791).Compared with the control group,genotype and allele frequency of PRF1 rs885822 and STXBP2 rs10001 in MAS cases were statistical significantly different (rs885822:allele frequency x2=4.52,P=0.03 ; genotype frequency:x2=5.52,P=0.02.rs10001:allele frequencyx2=21.33,P=0.00; genotype frequency:x2=19.58,P=0.00).There was no statistical significant difference in genotype frequency and allele frequency of UNC13D rs3744007 and STXBP2 rs6791 between the MAS and control group (rs3744007:allele frequencyx2=1.89,P=0.17; genotype frequency:x2=1.59,P=0.45.rs6791:allele frequency x2=l.69,P=0.19; genotype frequency:x2=2.09,P=0.35).Persistent fever,progressive hepatos-plenomegaly,a sharp decline in blood cells counts,pleural effusion,markedly increased serum liver enzymes,hyperlipidemia were the main characteristics.Some children had mucosal bleeding,neurological dysfunction.More than 82％ children had upper respiratory tract infection before the occurrence of MAS.90％ of children were in remission,while three children had multiple organ failure and died.Conclusion MAS is a fatal complication caused by immune disturbance.Early detection and tre-atment is the key to improve the prognosis.The SNP PRF1 rs885822 and STXBP2 rs1001 may be concurrent with the pathogenesis of SoJIA-MAS.The SNP UNC13D rs3744007 and STXBP2 rs6791 may not participate in the pathogenesis of SoJIA-MAS.

Exploration of immune function and its clinical significance in children with juvenile idiopathic arthritis / 中华实用儿科临床杂志

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.

Influence of rhTNFR:FC on expression of cartilage oligomeric matrix protein in synovial fluid and peripheral blood among juvenile idiopathic arthritis / 中华风湿病学杂志

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.

The influence of allergic rhinitis on patients with systemic onset juvenile idiopathic arthritis / 中华风湿病学杂志

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.

Associação entre artrite idiopática juvenil e osteogenesis imperfecta: relato de caso / Association between Juvenile idiopathic arthritis and osteogenesis imperfecta: case report

Os autores relatam o caso de uma paciente de 53 anos que apresenta uma rara associação entre artrite idiopática juvenil (AIJ) e osteogenesis imperfecta (OI), com acometimento poliarticular, incluindo a articulação temporomandibular. Apresentam uma revisão da literatura e uma discussão dos aspectos radiológicos do acometimento da referida articulação. Não foram encontrados relatos de casos com semelhante associação de doenças na literatura especializada.

The authors report a rare association case of juvenile idiopathic arthritis (JIA) and osteogenesis imperfecta (OI) in a 53 years-old female patient, present a literature review and discuss the radiological aspects of the temporo-mandibular joint involvement. To our knowledge, this is the first case report of JIA an OI association.

Changes of matrix metalloproteinase and cytokines and its clinical significance in children with juvenile idiopathic arthritis / 中华风湿病学杂志

Objective The purpose of the study was to investigate the changes and clinical significance of matrix metalloproteinase (MMP)-1,MMP-3,tissue inhibitor of metalloproteinase (TIMP),interleukin (IL)-1,tumor necrosis factor (TNF)-α and transforming growth factor(TGF)-β in juvenile idiopathic arthritis (JIA).Methods Thirty-two JIA subjects and 28 controls (traumatic arthritis patients) were included into this study.The MMP-1,MMP-3,TIMP,IL-1,TNF-α and TGF-β level in the serum and synovia were assessed by ELISA.The WBC count,the level of CRP,ESR,RF were also detected.Independent t-test and Pearson's analysis were adopted for data analysis.Results ① The level of MMP-1,MMP-3,IL-1 and TNF-α in the serum was (158±67) ng/ml,(212±89) ng/ml,(39±19) pg/ml,(26±10) pg/ml respectively,which was significantly higher than that of the control group (all P＜0.05) ; the ratio of MMP-3/TIMP-1 (0.86±0.32) was higher in the study group than that of the control group (P＜0.05),while the value of TIMP-1,TGF-β was (248±88),(17±9) ng/ml respectively,which was lower than that of the control group (P＜0.05).The value of seral MMP-3,MMP-3/TIMP-1 was positively correlated with that of WBC,CRP,ESR in the JIA group (all P＜0.05).② The value of MMP-1,MMP-3,IL-1 and TNF-α in the synovia was (216±78) ng/nl,(766±291)ng/ml,(56±21) pg/ml,(36±14) pg/ml respectively,which was higher than that of the control group (all P＜0.05); the ratio of MMP-3/TlMP-1 (2.68±0.89) was higher than that of the control group (P＜0.05),while the value of TIMP-1,TGF-β was (286±88) ng/ml,(12±4) ng/ml respectively,which was lower than that of the control group (all P＜0.05).③ The value of MMP-1,MMP-3,TIMP-1,IL-1 and TNF-α in the synovia was higher than that in the serum (all P＜0.05),while the value of TGF-β was lower than that in the serum (P＜0.05).Conclusion The value of MMP-1,MMP-3,IL-1 and TNF-α increases both in the serum and synovia,while the value of TIMP-1 decreases.The value of TGF-β decreases,which may have protective effect on JIA.The ratio of MMP-3/TIMP-1 in the serum is positively correlated to inflammation parameters,which may be used to judge the activity of illness in JIA.

Anestesia e artrite reumatoide / Anesthesia and rheumatoid arthritis / Anestesia y artritis reumatoide

JUSTIFICATIVA E OBJETIVOS: A artrite reumatoide (AR) é uma doença inflamatória crônica e de etiologia desconhecida. Os pacientes com AR são reconhecidos como pessoas com redução na expectativa de vida, em comparação com a população em geral. As doenças reumáticas são numerosas e ocorrem com alta variabilidade; algumas são desenvolvidas rapidamente; outras, cronicamente, provocando incapacidades durante toda a vida. Os riscos anestésicos, em desordens osteoarticulares, envolvem, além das deformidades mecânicas causadas pela doença, os sistemas cardiovascular, respiratório, renal e digestivo. CONTEÚDO: A proposta da presente revisão foi levantar a importância das fases da doença em processo, que podem influenciar no controle da anestesia antes, durante e após a cirurgia, destacando a experiência dos autores em uma avaliação retrospectiva dos casos de pacientes portadores de artrite reumatoide juvenil (ARJ) submetidos a próteses ortopédicas, com ênfase para as técnicas de intubação. CONCLUSÕES: Pacientes com artrite reumatoide podem apresentar um bom número de problemas complexos para o anestesiologista. Isso requer uma cuidadosa avaliação pré-operatória; a anestesia requer experiência com a técnica e o cuidado pós-operatório deve ser criteriosamente escolhido para atender à necessidade específica do paciente. O procedimento demanda efetiva comunicação entre cirurgião, reumatologista e anestesiologista, para que cada membro do grupo multidisciplinar contribua com sua experiência, visando a um melhor benefício ao paciente.

BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology. It is known that RA patients have a reduced life expectancy when compared with the general population. Rheumatic diseases are numerous and occur with high variability; some of them develop very rapidly while others occur chronically provoking disability throughout life. Anesthetic risks in osteoarticular disorders involve not only the mechanical deformations caused by the disease, but also the cardiovascular, respiratory, renal, and digestive systems. CONTENTS: The purpose of this review was to stress the importance of stages in disease process that may affect anesthesia control before, during, and after surgery, highlighting the authors' experience in a retrospective review of patients with juvenile rheumatoid arthritis (JRA) undergoing placement of orthopedic prosthesis with emphasis on intubation techniques. CONCLUSIONS: Rheumatoid arthritis patients can present a number of complex problems for the anesthesiologist. This requires careful preoperative evaluation; anesthesia requires experience with the technique; and postoperative care should be judiciously chosen to meet the specific needs of the patient. The procedure requires effective communication among surgeon, rheumatologist and anesthesiologist so each member of the multidisciplinary team can contribute with his/her expertise in order to better benefit the patient.

JUSTIFICATIVA Y OBJETIVOS: La artritis reumatoide (AR), es una enfermedad inflamatoria crónica y de etiología desconocida. Los pacientes con AR son reconocidos como personas que tienen una reducción en la expectativa de vida, en comparación con la población en general. Las enfermedades reumáticas son numerosas y ocurren con una alta variabilidad; algunas son desarrolladas rápidamente; otras, crónicamente, provocando incapacidades durante toda la vida. Los riesgos anestésicos, en los desórdenes osteoarticulares, involucran además de las deformidades mecánicas causadas por la enfermedad, los sistemas cardiovascular, respiratorio, renal y digestivo. CONTENIDO: La propuesta de la presente revisión fue destacar la importancia de las fases de la enfermedad en proceso, que pueden influir en el control de la anestesia antes, durante y después de la cirugía, destacando la experiencia de los autores en una evaluación retrospectiva de los casos de pacientes portadores de artritis reumatoide juvenil (ARJ), sometidos a prótesis ortopédicas, con énfasis en las técnicas de intubación. CONCLUSIONES: Los pacientes con artritis reumatoide pueden presentar un buen número de problemas complejos para el anestesiólogo. Eso requiere una cuidadosa evaluación preoperatoria; la anestesia necesita tener ya una experiencia con la técnica y el cuidado postoperatorio debe ser juiciosamente elegido para atender a la necesidad específica del paciente. El procedimiento exige una efectiva comunicación entre el cirujano, el reumatólogo y el anestesiólogo, para que cada miembro del grupo multidisciplinario contribuya con su experiencia, y así lograr un mejor beneficio para el paciente.

Artrodiastase para o tratamento da rigidez do quadril na artrite reumatoide juvenil (ARJ): resultados preliminares / Arthrodiastasis for the treatment of stiffness of the hip in juvenile rheumatoid arthritis (JRA): preliminary results

OBJETIVO: Apresentar os resultados preliminares da utilização da artrodiastase do quadril em pacientes portadores de artrite reumatoide juvenil e com comprometimento da articulação coxofemoral. MÉTODOS: Estudo prospectivo de 12 pacientes (seis meninos e seis meninas) com idades entre oito e 18 anos (média de 10,5 anos). Foi utilizado um fixador externo monolateral que permite os movimentos de flexão e de extensão no quadril. O fixador externo foi mantido por um período que variou de 78 a 90 dias, com média de 86 dias. O controle radiográfico foi realizado durante o ato operatório e, semanalmente, durante o período de tração e a cada quatro semanas, quando terminado este período. Na avaliação clínica dos resultados, incluímos a graduação da dor e o grau de movimentação articular, com medidas e avaliações pré e pós-operatórias. O período de acompanhamento variou de 12 a 15 anos, com média de 13 anos. RESULTADOS: O valor médio da escala de dor foi de nove (9) antes da operação e de quatro (4) no período pós-operatório. Em dois pacientes não ocorreu melhora da dor. O arco de movimento do quadril aumentou em todos os pacientes, com exceção de dois. Na avaliação radiográfica evidenciamos um aumento no espaço articular de 2mm, em média, e que se manteve no pós-operatório. Não foram observadas complicações com a utilização da técnica. Apenas verificamos soltura dos pinos de Schanz da região do osso ilíaco em dois pacientes. A técnica operatória não ocasionou resultado satisfatório. CONCLUSÃO: O procedimento de artrodiastase está bem indicado para a recuperação da mobilidade em uma articulação coxofemoral comprometida e rígida, como ocorre em pacientes com artrite reumatoide juvenil.

OBJECTIVE: To present the preliminary results of the use of hip arthrodiastasis in patients with juvenile rheumatoid arthritis and involvement of the hip joint. METHODS: A prospective study of 12 patients (six boys and six girls) aged between eight and 18 years (mean 10.5 years). We used a monolateral external fixator that allows flexion and extension at the hip. The external fixator was maintained for a period ranging from 78 to 90 days, with a mean of 86 days. Radiographic control was performed during surgery, weekly during the traction period, and every four weeks once this period was completed. The clinical evaluation of results included the degree of the pain and the degree of joint movement, measured and evaluatedpre-and post-operatively. The follow-up period ranged from 12 to 15 years, with a mean of 13 years. RESULTS: The average pain score was nine (9) before surgery and four (4) in the postoperative period. There was no improvement in pain in two patients. The range of motion of the hip increased in all patients except two. Radiographic evaluation evidenced a2 mm increase in joint space, on average,that has remained postoperatively. There were no complications with this technique. Only a loosening of the Schanz screws in the region of the iliac bone was observed in two patients. The surgical technique did not bring satisfactory results. CONCLUSION: The arthrodiastasis procedure is well suited for recovery of mobility in animpairedand rigid hip joint, as occurs in patients with juvenile rheumatoid arthritis.

Artrite idiopática juvenil em um serviço de reumatologia: Belo Horizonte, Minas Gerais / Juvenile idiopathic arthritis in a department of rheumatology:Belo Horizonte, Minas Gerais

O termo artrite idiopática juvenil (AIJ) descreve um grupo clinicamente heterogêneo de artrites com mais de seis semanas de duração, de causa desconhecida e início até os 16 anos de idade. Objetivo: descrever o perfil clínico de um grupo de pacientes com diagnóstico de AIJ. Métodos: os prontuários de 72 indivíduos foram revistos com o objetivo de classificá-los conforme critérios propostos pelo ILAR. Os dados obtidos foram comparados com a literatura. Resultados: eram 37 crianças (51,4%) do sexo masculino e 35 do sexo feminino, com mediana de idade de 164,5 meses; 23 (31,9%) estavam classificados como sistêmicos, 25 (34,7%) como oligoarticulares, três (4,2%) poliarticulares fator reumatoide positivo, 13 (18,1%) poliarticulares fator reumatoide negativo, três (4,2%) com artrite psoriásica, quatro (5,6%) com artrite associada à entesite e um (1,4%) com doença indiferenciada. O fator reumatoide foi positivo em 10 (13,9%) e o FAN em 14 (19,4%). Uveíte crônica foi encontrada em quatro (5,6%) crianças, todas do sexo feminino (p=0,05), com doença iniciada antes dos quatro anos de idade (p=0,03) e com FAN positivo (p < 0,001). Conclusão: sabe-se que há diferenças na prevalência e na distribuição dos subtipos de AIJ dependendo da origem da população. Os dados analisados neste estudo, o primeiro do gênero em nosso país, indicaram importantes diferenças entre os diversos grupos geográficos/étnicos acometidos pela AIJ, sugerindo a influência de fatores genéticos, associados ou não a fatores ambientais, que deverão ser estudados e confirmados posteriormente, na expressão da AIJ.

The term Juvenile Idiopathic Arthritis (JIA) describes an arthritis clinically heterogeneous group of over six week?s duration, unknown causes and beginning up to 16 years old. Objective: to describe the clinic profile of a patients? group with JIA diagnosis. Methods: the records of 72 individuals were reviewed with the aim of classifying them according to the ILAR proposed criteria. The collected data were compared with the literature. Results: there was 37 male children (51,4%) and 35 female, with the mean age of 164,5 months; 23 (31,9%) were classified as systemic, 25 (34,7%) as oligoarticular, three (4,2%) as polyarticular positive rheumatoid factor, 13 (18,1%) polyarticular negative rheumatoid factor, three (4,2%) psoriatic arthritis, four (5,6%) with arthritis associated to enthesitis and one (1,4%) with indifferenced disease. The rheumatoid factor was positive in 10 (13,9%) and the FAN in 14 (19,4%). Chronic uveitis was found in four (5,6%) children, all female (p=0,05), with the disease started before four years old (p=0,03) and with positive FAN (p < 0,001). Conclusion: it is known that there are differences in the prevalence and distribution of the JIA subtypes depending on the population origins. The data analyzed in this study, the first of the kind in our country, indicate relevant differences between the several geographic / ethnical groups affected by the JIA, suggesting the influence of docugenetic factors, whether associated or not to environmental factors, which must be further studied and confirmed.