FRI0463 IDENTIFICATION OF EARLY CLINICAL AND LABORATORY CHARACTERISTICS OF MACROPHAGE ACTIVATION SYNDROME ASSOCIATED WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

Abstract

Background:Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of systemic juvenile idiopathic arthritis (SJIA). However, early recognition of MAS remains challenging. Because it is clinically heterogeneous, hemophagocytosis is often not detected, and histopathological features lack the specificity associated with hemophagocytic syndromes. In addition, it is often difficult to distinguish early MAS from SJIA or sepsis-like syndromes.Objectives:To identify early clinical and laboratory characteristics of MAS associated with SJIA.Methods:This is a retrospective cohort study of 149 SJIA patients treated at the Children’s Hospital of Zhejiang University School of Medicine between January 2010 to December 2017. All patients fulfilled 2001 ILAR criteria for SJIA, and 27 fulfilled 2016 Classification Criteria for MAS. We evaluated the clinical and laboratory features of SJIA patients with MAS and compared them to those without MAS. We focused our analysis on early MAS, which was defined as the time when the initial clinical and/or laboratory abnormalities suggestive of MAS were first detected.Results:The clinical features associated with early MAS were hypotension, absence of arthritis and lymphadenopathy, bone marrow hemophagocytosis, central nervous system dysfunction, and gastrointestinal involvement. The best laboratory parameters for early MAS detection were platelet counts ≤275.0 × 109/L, lactate dehydrogenase >596.0 U/L, aspartate aminotransferase >47.0 U/L, erythrocyte sedimentation rates ≤41.0 mm/h, ferritin >1400.0 ng/mL, D-dimer >1.40 mg/L, triglyceride >1.30 mmol/L, alanine aminotransferase >33.0 U/L, C-reactive protein ≤68.0 mg/L, fibrinogen ≤4.1 g/L, absolute neutrophil counts ≤5.2 × 109/L, serum total protein ≤66.0 g/L, and white blood cell ≤9.8 × 109/L. The combination of cytokines of IFN-γ >17.1 pg/mL and IL-10 >7.8 pg/mL were found to be a specific and good prognostic cytokine pattern for early recognition of MAS, the sensitivity and specificity as 71.4% and 98.2%.(Table 1, Fig 1, 2)Table 1.Identification of clinical and Cytokine characteristics differentiating patients with MAS onset from SJIA patients without MASCharacteristicsSensitivity (%)Specificity (%)OR (95% CI)p valueClinical characteristicsHypotension35.598.433.0 (6.8–160.1)0.000Absence of Arthritis77.485.219.8 (7.4–52.7)0.000Hemophagocytosis in the bone marrow28.697.314.5 (2.0–107.5)0.009Central nervous system involvement25.891.03.5 (1.3–9.7)0.015Gastrointestinal involvement22.691.83.3 (1.1–9.4)0.029Absence of lymphadenopathy77.451.62.6 (1.1–6.1)0.027Cytokine levelsIFN-γ >17.1 pg/mL82.183.649.5 (15.6–156.9)0.000IL-10 >7.8 pg/mL78.693.123.5 (7.9–69.5)0.000IFN-γ >17.1 pg/mL and IL-10 >7.8 pg/mL71.498.2142.5 (28.2–720.6)0.000OR, odds ratio. CI, confidence interval. PLT, platelet. LDH, lactate dehydrogenase. AST, aspartate aminotransferase. ESR, erythrocyte sedimentation rate. FER, ferritin. D-D, D-dimer. TG, triglycerides. ALT, alanine aminotransferase. CRP, C-reactive protein. FIB, fibrinogen. ANC, absolute neutrophil count; TP, total protein. WBC, white blood cells. ALB, albumin. IL, interleukin. IFN, interferon.Fig 1.Comparison of clinical characteristics in the MAS process. * P < 0.05. ** P < 0.01. CNS involvement: Central nervous system involvement.Fig 2.Comparison of serum cytokine levels in the MAS process. * P < 0.05. ** P < 0.01.Conclusion:Sudden hypotension, absence of arthritis, and significantly increased IFN-γ and IL-10 levels are important clinical and laboratory markers for early MAS identification in addition to the traditional features of SJIA-associated MAS.