Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Inoue, Natsumi; Shimizu, Masaki; Tsunoda, Shinichiro; Kawano, Mitsuhiro; Matsumura, Masami; Yachie, Akihiro

doi:10.1016/j.clim.2016.05.010

Cited by 112 publications

(83 citation statements)

References 47 publications

(60 reference statements)

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“…Likewise, adult-onset Still’s disease has complicated cytokine profiles. One study reported that patients with adult-onset Still’s disease could be divided into two types of disease according to distinct interleukin-6-based and interleukin-18-based cytokine profiles 32. As such, some patients with adult-onset Still’s disease might be well controlled by suppressing interleukin-18, if available.…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

et al. 2018

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ObjectiveTo evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still’s disease.MethodsIn this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still’s disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point.ResultsIn the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were –4.1 in the tocilizumab group and –2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still’s disease, drug eruption and anaphylactic shock.ConclusionThe study suggests that tocilizumab is effective in adult-onset Still’s disease, although the primary endpoint was not met and solid conclusion was not drawn.

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Section: Discussionmentioning

confidence: 99%

Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

et al. 2018

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“…In particular, serum IL‐1, IL‐6, and IL‐18 are correlated with disease activity and secondary complications . We previously reported increased serum IL‐18 in active s‐JIA and AOSD . Thus, serum IL‐18 is increasingly used as a biomarker for s‐JIA diagnosis and of its therapeutic response in s‐JIA .…”

Section: Discussionmentioning

confidence: 98%

FDG‐PET in macrophage activation syndrome associated with systemic juvenile idiopathic arthritis

Shimizu

Ikawa

Mizuta

et al. 2017

Pediatrics International

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We herein describe a case of systemic juvenile idiopathic arthritis (s-JIA)-associated macrophage activation syndrome (MAS) in which the fluorodeoxyglucose positron emission tomography ( FDG-PET) findings were characteristic. The pattern of greater FDG accumulation into the spleen compared with the liver was more remarkable in this patient compared with s-JIA. This pattern, however, was also observed in cases of acute leukemia. In the present patient, serum interleukin (IL)-18 was extremely elevated (255 000 pg/mL), whereas in leukemia patients it is mildly elevated (360-1480 pg/mL). FDG-PET might be a useful indicator of s-JIA and MAS in patients with fever of unknown origin. The pattern of FDG accumulation, however, can also be observed in acute leukemia. The combination of FDG-PET and serum IL-18 might be useful for the diagnosis of s-JIA and MAS.

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“…The candidate biomarkers included simple clinical laboratory markers, such as ESR, CRP, ferritin, the neutrophil to lymphocyte ratio, and procalcitonin, as well as several cytokines or chemokines, such as IL-6, IL-8, CXC motif chemokine 13, and IL-18 [5, 21–23]. However, clinical laboratory markers are relatively nonspecific, and cytokine determinations are not clinically feasible.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are differences between JIA and AOSD, such as a higher seasonality in the former and a higher rate of pharyngitis in the latter [4]. A recent study compared the cytokine profiles of patients with AOSD and systemic JIA [5]. Among the shared features was a significant increase in interleukin 18 (IL-18) levels.…”

Section: Introductionmentioning

confidence: 99%

“…AOSD and systemic JIA are considered similar diseases with a shared pathogenesis and gene expression profile, but they are difficult to classify according to the criteria currently available [5, 7, 9]. Among the various clinical criteria for diagnosing AOSD, the Yamaguchi criteria are commonly used in clinical practice, and are the most widely cited; however, they require the prior exclusion of neoplasms, infections, and autoimmune diseases mimicking AOSD [7, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

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Application of the international league against rheumatism classification criteria for systemic juvenile idiopathic arthritis as a prognostic factor in patients with adults-onset Still’s disease

et al. 2018

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BackgroundAdult-onset Still’s disease (AOSD) is an adult form of systemic juvenile idiopathic arthritis (JIA) that differs from the latter in its classification. This study evaluated the concordance between the International League Against Rheumatism (ILAR) criteria for systemic JIA and the Yamaguchi criteria and then compared their possible prognostic value in patients with AOSD.MethodsIn a retrospective review of 169 adults with suspected AOSD, patients were classified according to the Yamaguchi or ILAR criteria. Then the concordance in cross-referencing the other group with the different criteria was investigated and the sensitivity and specificity of each set of criteria were determined. Disease activity markers in AOSD patients were correlated with positivity according to both systems.ResultsConcordance was good in patients with suspected AOSD (k = 0.7144, p < 0.001) and low in those with a diagnosis of AOSD (k = 0.3787, p < 0.001). The sensitivity of the ILAR criteria in AOSD patients was 0.8864 (95% confidence interval (CI): 0.8322–0.9405), and the specificity was 0.7838 (0.6511, 0.9164). Positivity according to the ILAR criteria correlated with the systemic score (r = 0.763, p < 0.0001) and C-reactive protein levels (r = 0.183, p = 0.0356) and was associated with a relapse (odds ratio: 1.589, 95% CI: 1.043–2.421), macrophage activation syndrome (MAS; odds ratio: 1.993, 95% CI: 1.218–3.263) and care in the intensive care unit (ICU; odds ratio: 2.087, 95% CI: 1.086–4.011).ConclusionsIn AOSD patients, there is fair concordance between the Yamaguchi and ILAR criteria for systemic JIA. Positive ILAR criteria may be useful for identifying AOSD patients at high risk for relapse, MAS and the need for ICU care. Further studies including larger populations from several centers are needed to confirm our results regarding the utility of the ILAR criteria in AOSD patients.

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Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Cited by 112 publications

References 47 publications

Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

FDG‐PET in macrophage activation syndrome associated with systemic juvenile idiopathic arthritis

Application of the international league against rheumatism classification criteria for systemic juvenile idiopathic arthritis as a prognostic factor in patients with adults-onset Still’s disease

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