inhibition. Moreover, a combination of biomarkers including WBC, CRP, ferritin and LDH may be useful for the diagnosis of flare.A lack of biomarkers during tocilizumab treatment in inflammatory diseases has been a problem for clinical practice. Especially for large vessel vasculitis and adultonset Still's disease, the evaluation of disease activity is more dependent on acute-phase reactants in blood tests than RA. Our study showed that the CRP levels reflected disease activity under treatment with an IL-6 inhibitor only slightly, as was expected. Alternatively, LDH was identified as a potential biomarker to detect flare. LDH is an enzyme that exists abundantly in reticulocytes, the heart, lungs, muscles and liver, but is distributed in almost all types of organ cells. We assume that LDH elevation in active adult-onset Still's disease not only reflects liver involvement, but also is derived from systemic inflammation of multiple organs, caused by inflammatory cytokines. Indeed, LDH elevation has been reported to be relevant to systemic inflammation [6,7] and macrophage-activated syndrome [8]. Another important suggestion of our study was that a very subtle increase in CRP levels could indicate worsening in adult-onset Still's disease under tocilizumab treatment. The CRP level at relapse in tocilizumab(+) was only 0.1 mg/dl, but the increase from 0.01 mg/dl before relapse was significant.Our data is not confirmatory, due to the nature of a retrospective study with a small sample size; however, we believe that serum LDH is a promising biomarker for flare in adult-onset Still's disease treated with an IL-6 inhibitor. Since adult-onset Still's disease is a rare disease, and a flare during anti-IL-6 treatment is much rarer [4], cooperation to accumulate cases is necessary to validate our data.
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