Derivation and validation of four patient clusters in Still’s disease, results from GIRRCS AOSD-study group and AIDA Network Still Disease Registry

• DOI: 10.1136/rmdopen-2023-003419
• Publication Date: 2023-11-21T05:05:15Z
• Authors: Piero Ruscitti; Francesco Masedu; Antonio Vitale; Ilenia Di Cola; Valeria Caggiano; Claudia Di Muzio; Paola Cipriani; Marco Valenti; Onorina Berardicurti; Luca Navarini; Daniela Iacono; Ilenia Pantano; Daniele Mauro; Francesco Ciccia; Silvia Rossi; Ludovico De Stefano; Sara Monti; Serena Bugatti; Carlomaurizio Mon...; Francesco Caso; Luisa Costa; Marcella Prete; Federico Perosa; Annamaria Iagnocco; Fabiola Atzeni; Giuliana Guggino; Henrique Giardini; Isabele Parente d...; Ibrahim A Almaghl...; Kazi Asfina; Haner Direskeneli; Fatma Alibaz-Oner; Gizem Sevik; Abdurrahman Tufan; Petros P Sfikakis; Francesco La Torre; Andrea Hinojosa-A...; Eduardo Martín-Nares; Jiram Torres-Ruiz; Gafaar Ragab; Maria Cristina Ma...; Joanna Makowska; Emanuela Del Giudice; Elena Bartoloni; Giacomo Emmi; Marcello Govoni; Alberto Lo Gullo; Giuseppe Lopalco; Gabriele Simonini; Lampros Fotis; Benson Ogunjimi; Samar Tharwat; Bruno Frediani; Armin Maier; Francesco Carubbi; Lorenzo Dagna; Sukran Erten; Antonio Gidaro; José Hernández-Ro...; Paolo Sfriso; Claudia Fabiani; Roberto Giacomelli; Luca Cantarini
• Keywords: Adult-Onset; myalgia; Fever; Immunology; Juvenile; Cluster (spacecraft); Erythrocyte sedimentation rate; Arthritis, Arthritis, Juvenile, Still's Disease, Adult-Onset; Settore MED/38 - Pediatria Generale E Specialistica; Rash; Observational study; Health Sciences; Humans; Disease; Prospective Studies; Internal medicine; Immunology and Microbiology; Sore throat; Ferritin; Arthritis; FOS: Clinical medicine; NK Cell Recognition; R; Life Sciences; Pharyngitis; Myalgia; Hematology; Exanthema; Still's Disease; Computer science; Arthritis, Juvenile; 3. Good health; Programming language; Autoinflammatory Disorders; C-Reactive Protein; Ferritins; Medicine; Hemophagocytic Lymphohistiocytosis and Related Disorders; Surgery; Arthritis; Arthritis, Juvenile; Still's Disease, Adult-Onset; Still's Disease, Adult-Onset; Diagnosis and Management of Kawasaki Disease; Natural Killer Cells in Immunity

BackgroundDifferent patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still’s disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients.MethodsPatients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters.ResultsK-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients.ConclusionsFour patient clusters in Still’s disease may be recognised by a multidimensional characterisation (‘Juvenile/Transitional’, ‘Uncomplicated’, ‘Hyperferritinemic’ and ‘Catastrophic’). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.