IL-18 distinguishes MAS from fHLH during active hyperferritinemia. Serum samples from a cohort of healthy controls (HCs) and patients with active sJIA, MAS, IA-HLH, and fHLH were probed for (A) total IL-18, (B) IL-18 binding protein, (C) free IL-18, and (D) CXCL9. See Data supplement A for clinical details. (E) A receiver operating characteristic (ROC) for total IL-18 distinguishing MAS from fHLH was calculated. (F) Total IL-18/CXCL9 ratios were computed and (G) a ROC for this ratio distinguishing MAS from fHLH was calculated. ★Optimal cutoff of 2.3. All concentrations are in picogram/milliliter. *P < .05, **P < .01, ***P < .001, ****P < .0001 by Kruskal-Wallis test with Dunn multiple comparisons posttest, except for ROC analysis. All differences meeting corrected threshold of P < .05 between individual groups are shown except comparisons made to HC for total IL-18 and CXCL9. The open circle in MAS represents systemic lupus erythematosus–associated MAS; all others are sJIA-MAS. Open circles in fHLH represent plasma samples. AUC, area under curve.