TY - JOUR

T1 - Smoking associates with distinct clinical phenotypes in patients with systemic lupus erythematosus

T2 - A nationwide Danish cross-sectional study

AU - Leffers, Henrik Christian Bidstrup

AU - Troldborg, Anne

AU - Voss, Anne

AU - Kristensen, Salome

AU - Lindhardsen, Jesper

AU - Kumar, Prabhat

AU - Linauskas, Asta

AU - Juul, Lars

AU - Krogh, Niels Steen

AU - Deleuran, Bent

AU - Dreyer, Lene

AU - Jacobsen, Søren

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - autoimmune diseases

KW - lupus nephritis

KW - smoking

KW - systemic lupus erythematosus

U2 - 10.1136/lupus-2021-000474

DO - 10.1136/lupus-2021-000474

M3 - Journal article

C2 - 33811110

AN - SCOPUS:85103785490

VL - 8

JO - Lupus Science and Medicine

JF - Lupus Science and Medicine

SN - 2053-8790

IS - 1

M1 - e000474

ER -