• cluster analysis
• disease clinical phenotypes
• severe flares
• systemic lupus erythematosus

Objectives: To describe different clinical phenotypes of severe flares in a monocentric cohort of SLE patients and to evaluate treatment and outcomes.
Material and methods: Retrospective study of prospectively collected data about 122 severe SLE flares followed for 12 months. Baseline characteristics included disease activity assessment by SELENA SLEDAI and BILAG 2004 scores, demographic and laboratory data. A hierarchical unsupervised segmentation method was applied to cluster flares based on baseline features. Treatments and outcomes according to LLDAS, DORIS Remission and SRI definitions, were compared among clusters at different timepoints.
Results: We identified 3 disease clusters, 2 composed mainly by extra-renal flares, and one by renal flares. Among non-renal clusters, Cluster 1 was characterized by severe constitutional symptoms occurring in younger patients, presenting marked inflammatory biomarkers and multiple autoantibodies specificities. Cluster 2 included flares with lower disease activity, presenting mild clinical manifestations, mainly mucocutaneous and musculoskeletal, and antiphospholipid syndrome (APS) overlap. Cluster 3 was the renal flares cluster.
Cluster 1 and the renal Cluster were treated more frequently with GCs pulses and MMF, presenting higher daily and cumulative GCs doses at 12 months. Moreover, they shared a similar percentage of attainment of LLDAS (about 50%) and remission (about 35% both).
Conclusions: This study describes three different phenotypes of severe flares in SLE in a real-life setting. Our results could potentially represent a clinical starting point, in the contest of precision medicine, for better understanding analogies and differences in severe presentation of this multifaceted disease, on which to stratify and build tailored treatment strategies.