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

RMD Open. 2023 Nov;9(4):e003419. doi: 10.1136/rmdopen-2023-003419.

Abstract

Background: Different 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.

Methods: Patients 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.

Results: K-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.

Conclusions: Four 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.

Keywords: Arthritis; Arthritis, Juvenile; Still's Disease, Adult-Onset.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Arthritis, Juvenile* / complications
  • C-Reactive Protein / metabolism
  • Exanthema* / complications
  • Ferritins
  • Fever
  • Humans
  • Myalgia / complications
  • Pharyngitis* / complications
  • Prospective Studies
  • Still's Disease, Adult-Onset* / complications
  • Still's Disease, Adult-Onset* / diagnosis
  • Still's Disease, Adult-Onset* / epidemiology

Substances

  • C-Reactive Protein
  • Ferritins