Macrophage Activation Syndrome In Systemic Juvenile Idiopathic Arthritis Research Articles

Are the 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome applicable to patients with adult-onset Still's disease?

The objectives of this study are to determine whether the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (SJIA) can be used to identify MAS in patients with adult-onset Still's disease (AOSD). Using laboratory data from 76 AOSD patients with and without MAS, we analyzed the ability of the collective and individual constitutive elements of the 2016 MAS in SJIA criteria and additional laboratory measures to discriminate between AOSD patients with (n = 16) and without (n = 60) MAS. Cutoff values to determine the sensitivity, specificity, and predictive values were calculated from receiver operating characteristic curves, and modified classification criteria for MAS in AOSD were evaluated. The 2016 MAS in SJIA classification criteria had an overall sensitivity of 100%, specificity of 70.0%, positive predictive value of 47.1%, and negative predictive value of 100% to discriminate between AOSD patients with and without MAS based on laboratory data. Among the individual criteria, the sensitivity of triglycerides (46.7%) and the specificity of ferritin (15.0%) for MAS in AOSD were particularly low. The sensitivity and specificity for classifying MAS in AOSD patients were increased to 100 and 93%, respectively, by excluding triglycerides and changing the cutoff values for other criteria in the 2016 MAS in SJIA classification. The 2016 classification criteria for MAS in SJIA had higher sensitivity but lower specificity to identify MAS in AOSD patients compared with SJIA patients.

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and...

Identification of the best cutoff points and clinical signs specific for early recognition of macrophage activation syndrome in active systemic juvenile idiopathic arthritis

ObjectivesThe purpose of our study was to detect early clinical and laboratory signs that help to discriminate macrophage activation syndrome (MAS) from active systemic juvenile idiopathic arthritis (SJIA) without MAS. MethodsOur retrospective study was based on reviewing the medical charts of the children admitted to the rheumatology department with active SJIA and definite MAS (n = 18) and without MAS (n = 40). We evaluated the data related to SJIA and MAS at the moment of the patient׳s admission. If the patient had signs of MAS since admission or developed definite MAS later during this flare, he was referred to the main group. The children who did not have MAS during the flare episode and did not have MAS in the past medical history were in the control group. We calculated the cutoff points for MAS parameters, performed the analysis of sensitivity and specificity, identified the predictors, and provided the preliminary diagnostic rule through “the-number-of-criteria-present” approach. ResultsThe clinical signs were relevant to MAS in SJIA: oligoarticular disease course (OR = 5.6), splenomegaly (OR = 67.6), hemorrhages (OR = 33.0), and respiratory failure (OR = 11.3). The involvement of wrist (OR = 0.2), MCP (OR = 0.1), and PIP joints (OR = 0.1) was protective against MAS development. The best cutoffs for laboratory parameters were PLT ≤ 211 × 109/l, WBC ≤ 9.9 × 109/l, AST > 59.7U/l, LDH > 882U/l, albumin ≤ 2.9g/dl, ferritin > 400μg/l, fibrinogen ≤ 1.8g/l, and proteinuria. The laboratory variables were more precise in the discrimination of early MAS than clinical: any 3 or more laboratory criteria provided the highest specificity (1.0) and sensitivity (1.0) and OR = 2997. ConclusionsWe detected clinical and laboratory markers and created preliminary diagnostic (laboratory) guidelines for early discrimination of MAS in active SJIA.

Identification of the best cut-off points and clinical signs specific for early recognition of macrophage activation syndrome in active systemic juvenile idiopathic arthritis

Macrophage activation syndrome (MAS) – is a severe life-threatening hematological condition, mostly complicated systemic juvenile idiopathic arthritis (SJIA). Early detection of MAS can lead to appropriate therapeutic interventions and change the outcomes. There are no strict criteria for early MAS detection in SJIA. Currently applied HLH criteria can determinate only advanced stage of MAS, which lead to delay diagnosis, late start of specific treatment and associated with poor outcomes. There are several sets of preliminary criteria of MAS in SJIA.

FRI0528 Canakinumab in Systemic Juvenile Idiopathic Arthritis: Impact on the Rate and Clinical Presentation of Macrophage Activation Syndrome

BackgroundCanakinumab is a fully human, selective, anti-IL-1β monoclonal antibody approved for the treatment of patients with systemic juvenile idiopathic arthritis (SJIA). In the phase III trials, macrophage activation syndrome (MAS),...

A98: Rescue Treatment by Increased Doses of IL‐1 Inhibitors for Macrophage Activation Syndrome in Children With Systemic Juvenile Idiopathic Arthritis

Background/Purpose:macrophage activation syndrome (MAS) is a life‐threatening complication of systemic juvenile idiopathic arthritis (SJIA). More than half cases of MAS are steroid‐resistant and required to use second‐line agents, such as cyclosporine A (CsA), intravenous immunoglobulin (IVIG) and biologic agents. Known interleukin‐1 (IL‐1) is the key cytokine in pathogenesis of MAS and SJIA, so anti‐IL‐1 treatment considered as potential effective treatment. There are several publication about efficacy of increased doses of anakinra during the MAS episodes. Data about efficacy others new IL‐1 blockers (canakinumab and rilonacept) for MAS in SJIA are limited. There are only several cases of MAS during and after canakinumab (CNKB) treatment of SJIA in randomized controlled trials.Methods:a retrospective study of the clinical notes, reports of laboratory investigations and radiological images. We included 3 patients with SJIA who developed MAS. First patient (Pt#1) had the severe form of MAS, resistant to high doses of steroids, IVIG, CsA. After failure of previous treatment anakinra was added, and later changed on CNKB. Second patient (Pt#2) developed SJIA flare with severe MAS after 3rd CNKB injection, resistant to high doses steroids, IVIG, required Fresh Frozen Plasma, third patient (Pt#3) developed only mild MAS after 8th CNKB injection without signs of SJIA flare. Indications for increased doses of CNKB were inefficacy of previous anti IL‐1 treatment in standard and increased doses and severity of MAS (Pt#1, Pt#2) according the manufacture's manual permitted to use the maximum dose of 300 mg per injection. The initial CNKB dose before MAS was 4 mg/kg every 4 weeks in Pt#2 and Pt#3. All patient during the MAS received one single injection of increased dose of CNKB: 15 mg/kg (Pt#1), 12.5 mg/kg (Pt#2) and 7.5 mg/kg (Pt#3). CNKB was injected every 4 weeks with gradually tapering dose up to 4 mg/kg every 4 weeks. All parents signed the inform consent. Institutional Review Board affirmed this kind of treatment.Results:in Pt#1 initial treatment with standard doses of anakinra was insufficient and dose was increased up to 20 mg/kg/day with good response. Later anakinra was changed on CNKB in 1st dose 15 mg/kg every 4 weeks with gradually tapering dose up to 6 mg/kg up to now. The switching from anakinra to CNKB did not loose the efficacy. In Pt#2 after initiation of increased dose of CNKB the flare of JIA and active MAS was dramatically abrupt up to 7th day after 1st injection. Total normalization of lab tests occurred in 2 weeks. After normalization we tapered corticosteroids. In Pt#3 MAS also quickly disappeared, the normalization of lab test also occurred in 10 days. No side and adverse effects were noticed during using of increased anakinra and CNKB doses.Conclusion:SJIA and MAS are both IL‐1‐ dependent conditions. The SJIA flare and MAS usually associated with increased production of pro‐inflammatory cytokines, especially IL‐1β. So we suppose that increased levels of IL‐1β require increased doses of IL‐1 blockers. Our data shows the efficacy and safety of increased doses of IL‐1 blockers. It is necessary to provide future trials to evaluate the efficacy and safety increased doses of IL‐1 blockers for treatment MAS in SJIA.