Figure 4.

Association between unusual features and pre-exposure to anti-IL-1/IL-6 or MAS at sJIA onset. (A) Heat map indicating occurrence of unusual clinical and radiological features (rows) by subjects (columns), grouped by pre-exposure status. (B) Statistical analysis for panel A, indicating p values, FDR and OR with 95% CI. Inf, infinite, #p<0.1, *p<0.05, **p<0.01, ***p<0.001. (C–F) Comparison of severity-related features in pre-exposed LD cases versus published sJIA cohorts. (C) Pre-exposed LD cases compared with Janow et al⁴² (D) Pre-exposed LD cases with sJIA onset <1.5 years, compared with comparable age group in Russo and Katsicas⁴³; cut-off at <1.5 years was chosen by Russo and Katsicas, based on developmental difference before versus after 18 months. (E) Pre-exposed LD cases with sJIA onset >1.5 years, compared with comparable age group in Russo and Katsicas.⁴³ (F) Pre-exposed LD cases treated with IL-1/IL-6 inhibitors for ≥6 months compared with comparable groups in Pardeo et al⁸⁴ and Nigrovic et al.⁸⁰ No bar indicates unavailable data. For details on definitions and published cohorts, see online supplementary table S6. (G) Statistical analysis of associations between MAS at sJIA onset and unusual clinical features of LD in sJIA, indicating p values, FDR and OR with 95% CI. FDR, false discovery rate; HELN, hyperenhancing lymph nodes; IL, interleukin; LD, lung disease; MAS, macrophage activation syndrome; PAP/ELP, pulmonary alveolar proteinosis/endogenous lipoid pneumonia; sJIA, systemic juvenile idiopathic arthritis.