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.

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

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

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

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

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

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