Juvenile neuropsychiatric systemic lupus erythematosus: identification of novel central neuroinflammation biomarkers

International audienceIntroduction Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated. Objectives To identify central nervous system (CNS) disease biomarkers of j-NPSLE. Methods A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations. Results Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone ( p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested ( n = 10). Both biomarkers correlated strongly with each other ( R s = 0.832, p < 0.0001, n = 23 paired samples). Conclusion CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE

Acute monoarthritis in young children: comparing the characteristics of patients with juvenile idiopathic arthritis versus septic and undifferentiated arthritis

International audienceAcute arthritis is a common cause of consultation in pediatric emergency wards. Arthritis can be caused by juvenile idiopathic arthritis (JIA), septic (SA) or remain undetermined (UA). In young children, SA is mainly caused by Kingella kingae (KK), a hard to grow bacteria leading generally to a mild clinical and biological form of SA. An early accurate diagnosis between KK-SA and early-onset JIA is essential to provide appropriate treatment and follow-up. The aim of this work was to compare clinical and biological characteristics, length of hospital stays, duration of intravenous (IV) antibiotics exposure and use of invasive surgical management of patients under 6 years of age hospitalized for acute monoarthritis with a final diagnosis of JIA, SA or UA. We retrospectively analyzed data from < 6-year-old children, hospitalized at a French tertiary center for acute mono-arthritis, who underwent a joint aspiration. Non-parametric tests were performed to compare children with JIA, SA or UA. Bonferroni correction for multiple comparisons was applied with threshold for significance at 0.025. Among the 196 included patients, 110 (56.1%) had SA, 20 (10.2%) had JIA and 66 (33.7%) had UA. Patients with JIA were older when compared to SA (2.7 years [1.8-3.6] versus 1.4 [1.1-2.1], p < 0.001). Presence of fever was not different between JIA and SA or UA. White blood cells in serum were lower in JIA (11.2 × 109/L [10-13.6]) when compared to SA (13.2 × 109/L [11-16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 103 cells/mm3 [46-211] compared to JIA and UA (42 × 103 cells/mm3 [6.4-59.2] and 7.29 × 103 cells/mm3 [2.1-72] respectively), p < 0.001. Intravenous antibiotics were administered to 95% of children with JIA, 100% of patients with SA, and 95.4% of UA. Arthrotomy-lavage was performed in 66.7% of patients with JIA, 79.6% of patients with SA, and 71.1% of patients with UA. In children less than 6 years of age with acute mono-arthritis, the clinical and biological parameters currently used do not reliably differentiate between JIA, AS and UA. JIA subgroups that present a diagnostic problem at the onset of monoarthritis before the age of 6 years, are oligoarticular JIA and systemic JIA with hip arthritis. The development of new biomarkers will be required to distinguish JIA and AS caused by Kingella kingae in these patients

Early systemic inflammation induces neurodevelopmental disorders: results from ARTEMIS, a French multicenter study of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders and meta-analysis

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Early systemic inflammation induces neurodevelopmental disorders: results from ARTEMIS, a French multicenter study of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders and meta-analysis

International audienc

Early systemic inflammation induces neurodevelopmental disorders: results from ARTEMIS, a French multicenter study of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders and meta-analysis

International audienc