Plenary I: Lupus Manifestations and Comorbidities: How Have Our Strategies Improved?

Journal Information
Current Publisher: BMJ (10.1136)

Articles in this journal

Murray Urowitz
Plenary I: Lupus Manifestations and Comorbidities: How Have Our Strategies Improved?, Volume 6; doi:10.1136/lupus-2019-la.4

Abstract:
The prevalence of atherosclerotic vascular events (AVE) in a systemic lupus erythematosus (SLE) inception cohort in published literature is 10%.1 However this represents only clinically diagnosed events and gives no indication of the predisposition to such events. Furthermore there has been no study of changing prevalence of AVE over the past decades to the present. In this presentation the past prevalence AVE in the University of Toronto Lupus Cohort (UTLC) and the SLICC inception cohort will be described.2 It will then review the approaches for detecting subclinical atherosclerotic changes in SLE patients, which are the possible precursors to clinical events.3 Then the occurrence of AVE in patients with SLE prior to their diagnosis or in the first 2 years after their SLE diagnosis will be presented.4 5 Studies of incidence AVE in the systemic lupus international collaborating clinics (SLICC) cohort are dramatically lower than previously reported. However this cohort includes only inception cohorts seen in the current millennium. The UTLC was then studied for inception patients seen in two eras 1975–1987 and 1999–2011 and then followed for 6 years thus mirroring the SLICC cohort. Similar to the SLICC results the late UTLC revealed a four-fold decrease in AVE compared to its earlier cohort. This will be shown to be due in large part to the more effect management of the classic cardiovascular risk factors in the modern era. This offers significant hope for reducing the impact of this co-morbidity in patients with SLE. Learning objectives Describe the extent of clinical, subclinical and preclinical AVE in patients with SLE. Discuss the magnitude of the improvement in the incidence of AVE in patients with SLE in the modern era Explain the importance of effectively managing the classic cardiovascular risk factors in patients with SLE to minimize the occurrence of AVE References Sheane BJ.,Urowitz MB, Gladman DD, Atherosclerosis in Systemic Lupus Erythematosus – Epidemiology, Risk Factors, Subclinical Assessment and Future Study. Rheumatology: Current Research 2013;s5(01). Urowitz MB, Su J Gladman DD. Atherosclerotic Vascular Events in Systemic Lupus Erythematosus: An Evolving Story. The Journal of Rheumatology 2019, jrheum.180986. Tselios K, Sheane BJ, Gladman DD, Urowitz MB Optimal Monitoring For Coronary Heart Disease Risk in Patients with Systemic Lupus Erythematosus: A Systematic Review. The Journal of Rheumatology 2016;43(1):54–65. Urowitz MB, Gladman DD, Anderson NM, et al. Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort. Lupus Sci Med 2016;3(1):e000143. Tselios K, Gladman DD, Su J, et al. Evolution of Risk Factors for Atherosclerotic Cardiovascular Events in Systemic Lupus Erythematosus: A Longterm Prospective Study. The Journal of Rheumatology 2017;44(12):1841–49.
Zahir Amoura
Plenary I: Lupus Manifestations and Comorbidities: How Have Our Strategies Improved?, Volume 6; doi:10.1136/lupus-2019-la.5

Abstract:
Macrophage activation syndrome (MAS) is a life-threatening hyper-inflammatory syndrome characterised by excessive activation and proliferation of T lymphocytes and macrophages and a consequent massive production of cytokines, or ‘cytokine storm’. MAS is considered a secondary or acquired form of haemophagocytic lymphohistiocytosis (HLH) and is usually associated with infection (systemic Epstein-Barr virus or cytomegalovirus infections or tuberculosis), malignancy, or rheumatic diseases like systemic lupus erythematosus (SLE). SLE-MAS can occur both in adult and childhood-onset,1 2 at the time of diagnosis of SLE and frequently relapses in adults. There are no validated diagnostic or classification criteria for HLH/MAS in adults. HLH-2004 criteria developed for children are often used but are not sensitive enough to allow early diagnosis. These criteria include fever, splenomegaly, cytopenia affecting at least two lineages (hemoglobin 265 mg/dL) and/or hypofibrinogenemia (
George Bertsias
Plenary I: Lupus Manifestations and Comorbidities: How Have Our Strategies Improved?, Volume 6; doi:10.1136/lupus-2019-la.6

Abstract:
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 References Gonzalez LA, Alarcon GS. The evolving concept of SLE comorbidities. Expert review of clinical immunology 2017;13(8):753–68. 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. 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. 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. 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. 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. 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. 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. Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus...
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