Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Publisher Copyright: Copyright © 2014 by the American College of Rheumatology.Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections. Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA. Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.publishersversionPeer reviewe

La Relación neutrófilos/linfocitos y plaquetas/linfocitos y su correlación con los reactantes de fase aguda y la actividad de la enfermedad en pacientes con artritis reumatoide

Introducción. La relación neutrofilos/linfocitos (RNL) y plaquetas/linfocitos son medidas sensibles de inflamación. El objetivo de este estudio fue correlacionar la RNL y RPL con VSG, PCR y el índice de actividad de la enfermedad DAS-28 PCR, así como determinar los puntos de corte de la RNL y RPL indicativos de remisión de la enfermedad, actividad leve, moderada y severa determinada por DAS-28 PCR.   Pacientes y Métodos. Estudio retrospectivo en el que se evaluaron pacientes adultos con diagnóstico de AR. La correlación de la RNL y RPL con VSG, PCR y el índice de actividad de la enfermedad DAS-28 PCR se evaluó con test de Pearson. Los valores de corte de la RNL y RPL para discriminar actividad de la enfermedad (remisión, actividad baja, moderada y alta) se analizó con curvas ROC.   Resultados. Evaluamos 151 mediciones correspondientes a 55 pacientes. La RNL tuvo una correlación débil con VSG (r=0.065), PCR (r=0.23) y DAS-28 PCR (r=0.18). La RPL tuvo una correlación débil con VSG (r=0.22), moderada con PCR (r=0.38) y débil con DAS-28 PCR (r=0.20). El área bajo la curva de la RNL para discriminar remisión, actividad baja, moderada y severa fue de 0.61, 0.61, 0.58 y 0.35, respectivamente y para la RPL de 0.55, 0.55, 0.45 y 0.24, respectivamente.   Conclusión. En este estudio, la correlación entre RNL y RPL con reactantes de fase aguda y actividad de la enfermedad fue débil y la capacidad discriminativa para establecer el estado de actividad de la enfermedad fue baja. De acuerdo a estos resultados, estos indicadores no serían útiles para discriminar actividad de la enfermedad en pacientes con AR

Performance of Current Guidelines for Diagnosis of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis

ObjectiveTo compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. MethodsInternational pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician’s diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present. ResultsThe study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels 500 ng/ml discriminated best between MAS and systemic infections. ConclusionThe preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA

The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial

Abstract Background We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA). Methods In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP). Results At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders. Conclusion Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders. Trial Registration NCT00036374 </jats:sec

Performance of the Birmingham Vasculitis Activity Score and Disease Extent Index in childhood vasculitides

Objectives. To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. Methods. Patients fulfilling the EU-LAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schonlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis 1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. Conclusion. This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitide