Smoking associates with distinct clinical phenotypes in patients with systemic lupus erythematosus: a nationwide Danish cross-sectional study

Henrik Christian Bidstrup Leffers, Anne Troldborg, Anne Voss, Salome Kristensen, Jesper Lindhardsen, Prabhat Kumar, Asta Linauskas, Lars Juul, Niels Steen Krogh, Bent Deleuran, Lene Dreyer, Søren Jacobsen

6 Citations (Scopus)


OBJECTIVES: SLE displays large clinical heterogeneity that beyond genetic factors may be determined by environmental exposures. In this Danish nationwide study, we aimed to determine if clinical subsets of SLE were associated with smoking history.

METHODS: At each of six participating centres, incident or prevalent inpatients and outpatients with SLE were consecutively included. Manifestations forming the basis of SLE classification were registered in an electronic chart system. Patients also provided questionnaire-based data on environmental exposures, including smoking history. Hierarchical cluster analysis was conducted to determine and characterise subsets of patients with similar traits of disease manifestations. Levels of smoking exposure by pack-years were correlated to the identified SLE subsets, as well as discrete SLE manifestations.

RESULTS: The cohort consisted of 485 patients (88% women and 92% Caucasian) with SLE of which 51% were ever smokers. Common disease manifestations comprised non-erosive arthritis (81%), malar rash (57%), lymphopenia (55%), photosensitivity (50%) and persistent proteinuria (41%). We identified three distinct phenotypic clusters characterised by their preponderance of (A) neurological, serosal and mucosal involvement; (B) renal, haematological and immunological disorders; and (C) acute and chronic skin manifestations. Cluster B was the youngest and had the lowest level of smoking exposure. Age-adjusted regression analyses showed that compared with never smokers a smoking history of >20 pack-years was associated with neurological disorder (OR=3.16), discoid rash (OR=2.22), photosensitivity (OR=2.19) and inversely with haematological disorder (OR=0.40), renal disorder (OR=0.40) and non-erosive arthritis (OR=0.45), p<0.05 for all.

CONCLUSIONS: Our findings support that SLE presents in varying clinical phenotypes and suggest that they may have differentiated associations with smoking history.

Original languageEnglish
Article numbere000474
JournalLupus science & medicine
Issue number1
Publication statusPublished - 2 Apr 2021


  • Adult
  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • Denmark
  • Female
  • Humans
  • Lupus Erythematosus, Systemic
  • Male
  • Middle Aged
  • Phenotype
  • Smoking
  • Young Adult
  • autoimmune diseases
  • systemic lupus erythematosus
  • smoking
  • lupus nephritis


Dive into the research topics of 'Smoking associates with distinct clinical phenotypes in patients with systemic lupus erythematosus: a nationwide Danish cross-sectional study'. Together they form a unique fingerprint.

Cite this