Article Text

Download PDFPDF

03 Evidence-based treatment of SLE comorbidities
  1. George Bertsias
  1. Rheumatology, Clinical Immunology and Allergy, University of Crete Medical School, Greece and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), Greece


Patients with systemic lupus erythematosus (SLE) manifest increased frequency of several comorbidities, particularly cardiovascular diseases, infections, osteoporosis and fragility fractures, and also, malignant disorders such as lymphoma.1 Comorbid diseases may develop both early and later during the course of the disease due to complex interaction between lupus inflammation and administered treatments, especially glucocorticoids. Their prevention, early diagnosis and management is of great importance to ensure favourable long-term patient outcomes, as highlighted in the 2019 Update of the EULAR recommendations for the management of SLE.2 Despite extensive research, there is paucity of controlled studies to guide the treatment of comorbidities in SLE patients, and it remains elusive whether therapeutic goals (e.g. target levels of serum LDL-cholesterol) in SLE should be different than those in the general population.

The increased cardiovascular disease (CVD) burden seen in SLE patients emphasizes the need for primary prevention strategies cardiovascular disease. This includes the use of validated CVD risk prediction tools (e.g. Framingham Risk Score, Systematic COronary Risk Evaluation (SCORE), QRISK2), which however tend to underestimate the actual risk in patients with SLE.3 The role and indications in clinical practice for non-invasive modalities for assessing subclinical atherosclerosis (e.g. coronary artery assessment, carotid intima media thickness) is less clear.4 General non-pharmacological interventions include smoking cessation, avoidance of sedentary lifestyle and maintenance of ideal body mass index. High blood pressure should be adequately controlled preferentially with renin-angiotensin-aldosterone axis blockade, and dyslipidemia be treated with statins. Aspirin may be considered in SLE patients with high-risk antiphospholipid antibodies profile and/or high estimated CVD risk after careful evaluation of the bleeding risk.5 At the chronic maintenance stage, the dose of glucocorticoids should be minimized to less than 7.5 mg/day of prednisone equivalent. Importantly, hydroxychloroquine should be considered – unless contraindicated – in all cases due to its putative atheroprotective role.6

Infections and sepsis represent another important comorbidity associated with increased risk for hospitalization and death in patients with SLE.7 Application of general preventative strategies such as hygiene measures and immunizations cannot be overemphasized.8 Modification of SLE-related risk factors such as reduction of exposure to glucocorticoids and avoidance of treatment-related leukopenia/neutropenia are important.9 High-intensity immunosuppressive (high-dose azathioprine, mycophenolate, cyclophosphamide) or biologic (rituximab) therapies have also been associated with increased risk for infections, especially when used in combination with moderate or high doses of glucocorticoids10 11. Pre-emptive use of antibiotics is not recommended, nevertheless a low index of suspicion to diagnose an infection – including possible Pneumocystis pneumonia12 – and commence antibiotics promptly is warranted in high-risk groups including elderly or neutropenic patients, those with comorbidities (e.g. diabetes) or who are receiving glucocorticoids.

Osteoporosis and fragility fractures are potentially avoidable and readily treated comorbidities in patients with SLE.13 14 Factors impacting adversely on bone mass density, particularly chronic use of glucocorticoids, should be corrected.15 Osteoprotective and/or anti-osteoporotic interventions should be similar to those in the general population or patients with other chronic inflammatory disorders, yet caution is recommended in cases of kidney disease and reduced glomerular filtration rate. To this end, SLE patients should also be screened for vitamin D insufficiency, which should be corrected considering its presumed multifaceted effects on the disease.16

Learning objectives

  • Describe primary prevention strategies for SLE comorbidities including cardiovascular disease, infection and osteoporosis

  • Explain screening and treatment options for key comorbid diseases in patients with SLE


  1. Gonzalez LA, Alarcon GS. The evolving concept of SLE comorbidities. Expert review of clinical immunology 2017;13(8):753–68.

  2. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Annals of the rheumatic diseases2019;78(6):736–45.

  3. Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ2017;357:j 2099.

  4. Wu GC, Liu HR, Leng RX, et al. Subclinical atherosclerosis in patients with systemic lupus erythematosus: A systemic review and meta-analysis. Autoimmunity reviews 2016;15(1):22–37.

  5. Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis. JAMA 2019;321(3):277–87.

  6. Fasano S, Pierro L, Pantano I, et al. Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus. The Journal of rheumatology 2017;44(7):1032–38.

  7. Tektonidou MG, Wang Z, Dasgupta A, et al. Burden of Serious Infections in Adults With Systemic Lupus Erythematosus: A National Population-Based Study, 1996–2011. Arthritis care & research 2015;67(8):1078–85.

  8. van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Annals of the rheumatic diseases 2011;70(3):414–22.

  9. Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus 2013;22(12):1286–94.

  10. Jung JY, Yoon D, Choi Y, et al. Associated clinical factors for serious infections in patients with systemic lupus erythematosus. Sci Rep 2019;9(1):9704.

  11. Teh CL, Wan SA, Ling GR. Severe infections in systemic lupus erythematosus: disease pattern and predictors of infection-related mortality. Clinical rheumatology 2018;37(8):2081–86.

  12. Weng CT, Liu MF, Weng MY, et al. Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern Taiwan. J Clin Rheumatol 2013;19(5):252–8.

  13. Garcia-Carrasco M, Mendoza-Pinto C, Leon-Vazquez ML, et al. Incidence of Vertebral Fractures in Women with Systemic Lupus Erythematosus After 8 Years of Follow-Up. Calcif Tissue Int 2017;101(3):291–99.

  14. Mendoza-Pinto C, Rojas-Villarraga A, Molano-Gonzalez N, et al. Bone mineral density and vertebral fractures in patients with systemic lupus erythematosus: A systematic review and meta-regression. PloS one 2018;13(6):e0196113.

  15. Carli L, Tani C, Spera V, et al. Risk factors for osteoporosis and fragility fractures in patients with systemic lupus erythematosus. Lupus science & medicine 2016;3(1):e000098.

  16. Mak A. The Impact of Vitamin D on the Immunopathophysiology, Disease Activity, and Extra-Musculoskeletal Manifestations of Systemic Lupus Erythematosus. Int J Mol Sci 2018;19(8).

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.