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Systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein–Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.

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Figure 1: Clinical heterogeneity of SLE.
Figure 2: Immune dysfunction in SLE.
Figure 3: Typical malar rash in a patient with SLE.
Figure 4: Multifocal osteonecrosis in a patient with SLE following long-term corticosteroid treatment.
Figure 5: Stem cell transplantation in SLE.

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Introduction (A.K. and G.H.); Epidemiology (C.G.); Mechanisms/pathophysiology (M.K.C.); Diagnosis, screening and prevention (Z.T. and M.B.U.); Management (R.v.V.); Quality of life (G.R.-I.); Outlook (A.K.); Overview of Primer (A.K.).

Corresponding author

Correspondence to Arvind Kaul.

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Competing interests

A.K. has received honoraria for speaking as well as research grants from Janssen, Celgene, Pfizer and Wyeth. C.G. has received consulting fees and/or honoraria from Bristol-Myers Squibb (BMS), GlaxoSmithKline (GSK), Lilly, Merck Serono, Parexel and UCB and grant support from UCB. R.v.V. has received research support or grants from AbbVie, Amgen, BMS, GSK, Pfizer, Roche and UCB and consulting fees or honoraria from AbbVie, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB and Vertex. M.K.C. has received consulting fees or research support from AstraZeneca, BMS, GSK, Lilly, MedImmune, Novartis, Novo Nordisk and Pfizer. All other authors declare no competing interests.

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Kaul, A., Gordon, C., Crow, M. et al. Systemic lupus erythematosus. Nat Rev Dis Primers 2, 16039 (2016). https://doi.org/10.1038/nrdp.2016.39

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