Dissecting the clinical heterogeneity of adult-onset Still's disease, results from a multi-dimensional characterisation and stratification

Objectives. To stratify adult-onset Still’s disease (AOSD) patients in distinct clinical subsets to be differently man-aged, by using a multi-dimensional characterization.Methods.AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, la-boratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patientswere calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusterswere descriptively analysed for any possible difference.Results.Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash(92%) and arthritis (83%), with the highest ferritin levels [14 724 (6837) ng/mlAQ4]. In cluster 2, the onset was characterized by fever(100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10 (46.01) mg/l]. The patients incluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88 (1.70)] andthe highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster4, which was characterized by the lowest ferritin and CRP levels [1457 (1298) ng/ml and 54.98 (48.67) mg/l, respectively].Conclusion. Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with differentgenetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine ap-proach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization,which would drive a tailored therapeutic approach in these patients.