Managing the clinical heterogeneity of patients with Still's disease, from early diagnosis to timely treatment

Still's disease is an inflammatory syndrome affecting patients across all ages, previously known as systemic juvenile idiopathic arthritis (sJIA) in children and adult-onset Still's disease (AOSD) in adults. Multiple lines of evidence reported overlapping clinical features between sJIA and AOSD, commonly manifesting with daily fever, arthritis, evanescent salmon-coloured skin rash. The concomitant various degree of multiorgan involvement may increase the heterogeneity of the patient clinical picture. In active patients, a typical hyperferritinemia is recognized in association with increases of erythrocyte sedimentation rate and C reactive protein. Concerning pathogenesis, also in this case, similar mechanisms are reported in sJIA and AOSD involving both innate and adaptive arms of the immune systems; thus, Still's disease is peculiarly codified at the cross-road of autoinflammatory and autoimmune disorders. Furthermore, life-threatening complications burden the disease course in challenging the management of these patients, mainly macrophage activation syndrome, and worsening the prognosis. Concerning the treatment, glucocorticoids (GCs), conventional synthetic disease-modifying anti rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs), mainly IL-1 inhibitors, are administered to treat these patients. Usually, bDMARDs are considered in case of failure of GCs or GC-dependence. However, in some circumstances, bDMARDs may be administered as first-line modifying therapy without GCs, thus avoiding GC predictable side effects and optimizing the long-term outcome.

In this work, we aimed to synthetize the recent available literature considering the clinical management of patients with Still's disease, reviewing features about early diagnosis, optimal treatment algorithm, clinical therapeutic targets, treatment of complications, and patient monitoring in the follow-up.