Background Signs and symptoms establish the diagnosis of adult onset Still’s disease (AOSD) as well as of systemic onset juvenile idiopathic arthritis (sJIA). The published data regarding the importance of IL-18 as a marker for diagnosis and disease activity so far are conflicting. The aim of this study was to clarify the role of IL-18 as a diagnostic and disease activity marker in AOSD and sJIA. Methods Thirty adult patients diagnosed with AOSD and twenty children diagnosed with sJIA were included in the study. Clinical and laboratory data were obtained retrospectively for each patient visit whenever IL-18 serum levels were determined. IL-18 levels were determined by ELISA. Sixty-five adults and twenty-three children presenting with fever and/or arthritis who did not meet the criteria for a diagnosis of AOSD or sJIA served as comparison groups. Rau’s criteria and CRP values were used to evaluate disease activity. Results IL-18 levels were significantly elevated in patients with active AOSD compared to AOSD patients in remission and to the comparison group with a median of 16,327 pg/ml, 470 pg/ml, and 368 pg/ml, respectively ( p < 0.001). Analogous to AOSD in active sJIA, the median IL-18 serum level was significantly higher with 21,512 pg/ml than in the comparison group with 2580 pg/ml ( p < 0.001). At our cut-off point of 5000 pg/ml, the calculated specificity of IL-18 to establish the diagnosis of AOSD was 96.9%, and the sensitivity 63.3% (AUC = 0.870, p < 0.001). For the diagnosis of sJIA, a cut-off value of 10,000 pg/ml was chosen with a specificity of 100% and a sensitivity of 60% (AUC = 0.774, p = 0.003). At a cut-off value of 5000 pg/ml, the specificity was 62% and the sensitivity 65%. Conclusions This study gives further evidence to earlier publications of elevated IL-18 serum levels in active AOSD and sJIA, with up to 1000-fold higher concentrations compared to other rheumatic diseases. A clear association of IL-18 serum levels with disease activity in AOSD was found. The results support the use of IL-18 as an important biomarker in AOSD and sJIA. Electronic supplementary material The online version of this article (10.1186/s41927-019-0053-z) contains supplementary material, which is available to authorized users.

Background Establishing the diagnosis of Adult onset Still's disease is very challenging. Mostly it is still a diagnosis of exclusion. Along with IL-1, IL-6 and TNFα, IL-18 is one of the cytokines which seem to play a pivotal role in the pathogenesis of AOSD. It has been described as potential biomarker to support the diagnosis of AOSD. Regarding the importance of IL-18 as a marker for disease activity published data are so far conflicting. Objectives The aim of the study was to contribute to the understanding of the role of IL-18 as a diagnostic marker and its importance as a measure for disease activity in AOSD. Methods 30 patients (9 male, 21 female, mean age 41.7, range 19-74) diagnosed with AOSD in our Hospital from June 2007 - May 2013, were included in the study. 18 patients met Yamaguchi criteria, 2 would have met Yamaguchi criteria but had also positive anti-nuclear antibodies. For the remaining we adopted the diagnosis from the records. 20 patients were seen repeatedly. Medical records and laboratory analytes such as CRP, ESR, WBC were collected. IL-18 serum levels were determined using an IL-18 ELISA (MBL, Japan) according to the manufacturer's instructions. Additionally to the standard serum dilution (1:5) some samples were diluted up to 1:200. In two independent control cohorts (12 healthy controls, 10 RA patients) IL-18 serum levels were analyzed. Disease activity was evaluated with Rau's criteria and CRP values. Active disease was defined as a Rau's score ≥2 and/or CrP≥2 ULN. Results 22 out of 30 patients showed an active disease with a mean activity score of 3.5 (range 1-6) and a mean CRP value of 79.3 mg/l (range <5.0-208 mg/l), 8 patients were in remission (mean activity score 0.25 (range 0-1); mean CRP 5.7 mg/l (range <5-7.4), when seen for the first time. The mean IL-18 serum levels for all patients was 5705 pg/ml (range 100–408000 pg/ml). IL-18 levels were significantly increased in patients with active AOSD compared to patients in remission with a median of 17400 pg/ml (range 326-408000) and 373 pg/ml (range 100-1455 pg/ml), respectively. In comparison, the median IL-18 levels in the HC and RA cohort were 298 pg/ml and 312 pg/ml. In 14 patients with active disease at the first visit (Rau's score 3.6, range 0-6) the reduction of disease activity (Rau's score 0.3, range 0-2) was accompanied by a significant reduction in IL-18 serum levels from median of 19850 pg/ml (range 326 – 408000 pg/ml) to 462 pg/ml (range 20 – 7560 pg/ml) (paired sample T-test p<0.05), IL-18 levels of AOSD patients in remission remained stable. The levels of IL-18 were positively correlated with CRP levels (Pearson correlation, r=0.591, p<0.01) as well as percentage of neutrophils (r=0.434, p<0.05) and ferritin levels (r=0.550, p<0.01). Conclusions We could confirm earlier publications that high serum levels of IL-18 in active AOSD are detectable, with up to 1000fold higher concentrations compared to healthy controls and a patient cohort with a chronic inflammatory disease (RA). The results of our study clearly ...