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What Causes Lupus Flares?

  • Systemic Lupus Erythematosus (BN Cronstein and S Gay, Section Editors)
  • Published:
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Abstract

Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, follows a chronic disease course, punctuated by flares. Disease flares often occur without apparent cause, perhaps from progressive inherent buildup of autoimmunity. However, there is evidence that certain environmental factors may trigger the disease. These include exposure to UV light, infections, certain hormones, and drugs which may activate the innate and adaptive immune system, resulting in inflammation, cytotoxic effects, and clinical symptoms. Uncontrolled disease flares, as well as their treatment, especially with glucocorticoids, can cause significant organ damage. Tight surveillance and timely control of lupus flares with judicial use of effective treatments to adequately suppress the excessive immune system activation are required to bring about long term remission of the disease. We hope that new clinical trials will soon offer additional effective and target-specific biologic treatments for SLE.

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References

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  1. Stoll T, Sutcliffe N, Mach J, Klaghofer R, Isenberg DA. Analysis of the relationship between disease activity and damage in patients with systemic lupus erythematosus—a 5-yr prospective study. Rheumatology (Oxford). 2004;43(8):1039–44.

    Article  CAS  Google Scholar 

  2. Zhu TY, Tam L-S, Lee VWY, Lee KK, Li EK. Relationship between flare and health-related quality of life in patients with systemic lupus erythematosus. J Rheumatol. 2010;37(3):568–73.

    Article  PubMed  Google Scholar 

  3. Ruperto N, Hanrahan LM, Alarcón GS, et al. International consensus for a definition of disease flare in lupus. Lupus. 2011;20(5):453–62.

    Article  CAS  PubMed  Google Scholar 

  4. Buyon JP, Petri MA, Kim MY, et al. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. 2005;142(12 Pt 1):953–62.

    Article  CAS  PubMed  Google Scholar 

  5. Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353(24):2550–8.

    Article  CAS  PubMed  Google Scholar 

  6. Isenberg DA, Rahman A, Allen E, et al. BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group’s disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005;44(7):902–6.

    Article  CAS  Google Scholar 

  7. Thanou A, Chakravarty E, James JA, Merrill JT. How should lupus flares be measured? Deconstruction of the safety of estrogen in lupus erythematosus national assessment-systemic lupus erythematosus disease activity index flare index. Rheumatology (Oxford). 2014;53(12):2175–81.

    Article  Google Scholar 

  8. Isenberg DA, Allen E, Farewell V, et al. An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA. Ann Rheum Dis. 2011;70(1):54–9.

    Article  CAS  PubMed  Google Scholar 

  9. Laustrup H, Voss A, Green A, Junker P. SLE disease patterns in a Danish population-based lupus cohort: an 8-year prospective study. Lupus. 2010;19(3):239–46.

    Article  CAS  PubMed  Google Scholar 

  10. van den Berg L, Nossent H, Rekvig O. Prior anti-dsDNA antibody status does not predict later disease manifestations in systemic lupus erythematosus. Clin Rheumatol. 2006;25(3):347–52.

    Article  PubMed  Google Scholar 

  11. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30.

    Article  CAS  PubMed  Google Scholar 

  12. Manzi S, Sánchez-Guerrero J, Merrill JT, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012;71(11):1833–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet (London, England). 2011;377(9767):721–31. doi:10.1016/S0140-6736(10)61354-2.

    Article  CAS  Google Scholar 

  14. Welcher AA, Boedigheimer M, Kivitz AJ, et al. Blockade of interferon-γ normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. Arthritis Rheumatol (Hoboken, NJ). 2015;67(10):2713–22.

    Article  Google Scholar 

  15. Chiche L, Jourde-Chiche N, Whalen E, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol (Hoboken, NJ). 2014;66(6):1583–95.

    Article  CAS  Google Scholar 

  16. Crow YJ, Manel N. Aicardi-Goutières syndrome and the type I interferonopathies. Nat Rev Immunol. 2015;15(7):429–40.

    Article  CAS  PubMed  Google Scholar 

  17. Barbalat R, Ewald SE, Mouchess ML, Barton GM. Nucleic acid recognition by the innate immune system. Annu Rev Immunol. 2011;29:185–214.

    Article  CAS  PubMed  Google Scholar 

  18. Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009;461(7265):788–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pandey S, Kawai T, Akira S. Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors. Cold Spring Harb Perspect Biol. 2015;7(1):a016246. Excellent overview of extracellular and intracellular nucleic acid recognition pathways.

    Article  Google Scholar 

  20. Pazmandi K, Agod Z, Kumar BV, et al. Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells. Free Radic Biol Med. 2014;77:281–90.

    Article  CAS  PubMed  Google Scholar 

  21. Garcia-Romo GS, Caielli S, Vega B, et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med. 2011;3(73):73ra20.

    PubMed  PubMed Central  Google Scholar 

  22. Lande R, Ganguly D, Facchinetti V, et al. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med. 2011;3(73):73ra19.

    PubMed  PubMed Central  Google Scholar 

  23. Wang H, Li T, Chen S, Gu Y, Ye S. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin. Arthritis Rheumatol (Hoboken, NJ). 2015;67(12):3190–200.

    Article  CAS  Google Scholar 

  24. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity. 2007;40(8):560–6.

    Article  CAS  PubMed  Google Scholar 

  25. Rice GI, Rodero MP, Crow YJ. Human disease phenotypes associated with mutations in TREX1. J Clin Immunol. 2015;35(3):235–43.

    Article  CAS  PubMed  Google Scholar 

  26. Baechler EC, Batliwalla FM, Karypis G, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bennett L, Palucka AK, Arce E, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003;197(6):711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kirou KA, Lee C, George S, et al. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum. 2004;50(12):3958–67.

    Article  CAS  PubMed  Google Scholar 

  29. Feng X, Wu H, Grossman JM, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum. 2006;54(9):2951–62.

    Article  CAS  PubMed  Google Scholar 

  30. Landolt-Marticorena C, Bonventi G, Lubovich A, et al. Lack of association between the interferon-signature and longitudinal changes in disease activity in systemic lupus erythematosus. Ann Rheum Dis. 2008;68(9):1440–6.

    Article  PubMed  Google Scholar 

  31. Bauer JW, Petri M, Batliwalla FM, et al. Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum. 2009;60(10):3098–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Petri M, Singh S, Tesfasyone H, et al. Longitudinal expression of type I interferon responsive genes in systemic lupus erythematosus. Lupus. 2009;18(11):980–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Barr SG, Zonana-Nacach A, Magder LS, Petri M. Patterns of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1999;42(12):2682–8.

    Article  CAS  PubMed  Google Scholar 

  34. McKinney EF, Lee JC, Jayne DRW, Lyons PA, Smith KGC. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature. 2015;523(7562):612–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Petri MA, van Vollenhoven RF, Buyon J, et al. Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab trials. Arthritis Rheum. 2013;65(8):2143–53. This is a comprehensive analysis of clinical and laboratory predictors of lupus flare derived from patients enrolled in clinical trials of beliumumab.

    Article  CAS  PubMed  Google Scholar 

  36. Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Steiman AJ, Gladman DD, Ibañez D, Urowitz MB. Prolonged serologically active clinically quiescent systemic lupus erythematosus: frequency and outcome. J Rheumatol. 2010;37(9):1822–7.

    Article  PubMed  Google Scholar 

  38. Birmingham DJ, Irshaid F, Nagaraja HN, et al. The complex nature of serum C3 and C4 as biomarkers of lupus renal flare. Lupus. 2010;19(11):1272–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ho A, Magder LS, Barr SG, Petri M. Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum. 2001;44(10):2342–9.

    Article  CAS  PubMed  Google Scholar 

  40. Pan N, Amigues I, Lyman S, et al. A surge in anti-dsDNA titer predicts a severe lupus flare within Six months. Lupus. 2014;23(3):293–8.

    Article  CAS  PubMed  Google Scholar 

  41. Tseng C-E, Buyon JP, Kim M, et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(11):3623–32.

    Article  CAS  PubMed  Google Scholar 

  42. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. N Engl J Med. 1991;324(3):150-54.

  43. Foering K, Chang AY, Piette EW, Cucchiara A, Okawa J, Werth VP. Characterization of clinical photosensitivity in cutaneous lupus erythematosus. J Am Acad Dermatol. 2013;69(2):205–13.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kuhn A, Gensch K, Haust M, et al. Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: a randomized, vehicle-controlled, double-blind study. J Am Acad Dermatol. 2011;64(1):37–48.

    Article  CAS  PubMed  Google Scholar 

  45. Zahn S, Graef M, Patsinakidis N, et al. Ultraviolet light protection by a sunscreen prevents interferon-driven skin inflammation in cutaneous lupus erythematosus. Exp Dermatol. 2014;23(7):516–8.

    Article  CAS  PubMed  Google Scholar 

  46. Achtman JC, Werth VP. Pathophysiology of cutaneous lupus erythematosus. Arthritis Res Ther. 2015;17:182.

    Article  PubMed  PubMed Central  Google Scholar 

  47. LeFeber WP, Norris DA, Ryan SR, et al. Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes. J Clin Invest. 1984;74(4):1545–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994;179(4):1317–30.

    Article  CAS  PubMed  Google Scholar 

  49. Caricchio R, McPhie L, Cohen PL. Ultraviolet B radiation-induced cell death: critical role of ultraviolet dose in inflammation and lupus autoantigen redistribution. J Immunol. 2003;171(11):5778–86.

    Article  CAS  PubMed  Google Scholar 

  50. Lawley W. Rapid lupus autoantigen relocalization and reactive oxygen species accumulation following ultraviolet irradiation of human keratinocytes. Rheumatology. 2000;39(3):253–61.

    Article  CAS  PubMed  Google Scholar 

  51. Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon-α/β-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol. 2001;159(1):237–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vermi W, Lonardi S, Morassi M, et al. Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage. Immunobiology. 2009;214(9-10):877–86.

    Article  CAS  PubMed  Google Scholar 

  53. Meller S, Winterberg F, Gilliet M, et al. Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: an amplification cycle triggering cutaneous lupus erythematosus. Arthritis Rheum. 2005;52(5):1504–16.

    Article  CAS  PubMed  Google Scholar 

  54. Reefman E, Kuiper H, Limburg PC, Kallenberg CGM, Bijl M. Type I interferons are involved in the development of ultraviolet B-induced inflammatory skin lesions in systemic lupus erythaematosus patients. Ann Rheum Dis. 2008;67(1):11–8.

    Article  CAS  PubMed  Google Scholar 

  55. Zen M, Ghirardello A, Iaccarino L, et al. Hormones, immune response, and pregnancy in healthy women and SLE patients. Swiss Med Wkly. 2010;140(13-14):187–201.

    CAS  PubMed  Google Scholar 

  56. Jungers P. Lupus nephropathy and pregnancy. Arch Intern Med. 1982;142(4):771.

    Article  CAS  PubMed  Google Scholar 

  57. Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med. 2005;353(24):2539–49.

    Article  PubMed  Google Scholar 

  58. Lockshin MD. Pregnancy does not cause systemic lupus erythematosus to worsen. Arthritis Rheum. 1989;32(6):665–70.

    Article  CAS  PubMed  Google Scholar 

  59. Smyth A, Oliveira GHM, Lahr BD, Bailey KR, Norby SM, Garovic VD. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin J Am Soc Nephrol. 2010;5(11):2060–8.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Buyon JP, Kim MY, Guerra MM, et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann Intern Med. 2015;163(3):153–63. Largest and most methodologically rigorous cohort study examining pregnancy outcomes in patients with lupus, supporting the conclusion that pregnancy can be safely undertaken in patients with low disease activity at time of conception.

    Article  PubMed  Google Scholar 

  61. Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis Rheum. 1991;34(12):1538–45.

    Article  CAS  PubMed  Google Scholar 

  62. Ruiz-Irastorza G, Lima F, Alves J, et al. Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br J Rheumatol. 1996;35(2):133–8.

    Article  CAS  PubMed  Google Scholar 

  63. Saavedra MA, Sánchez A, Morales S, Navarro-Zarza JE, Ángeles U, Jara LJ. Primigravida is associated with flare in women with systemic lupus erythematosus. Lupus. 2015;24(2):180–5.

    Article  CAS  PubMed  Google Scholar 

  64. Koh JH, Ko HS, Kwok S-K, Ju JH, Park S-H. Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus. Lupus. 2015;24(2):210–7.

    Article  CAS  PubMed  Google Scholar 

  65. Chen S, Sun X, Wu B, Lian X. Pregnancy in women with systemic lupus erythematosus: a retrospective study of 83 pregnancies at a single centre. Int J Environ Res Public Health. 2015;12(8):9876–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Imbasciati E, Tincani A, Gregorini G, et al. Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome. Nephrol Dial Transplant. 2009;24(2):519–25.

    Article  PubMed  Google Scholar 

  67. Qian Q, Liuqin L, Hao L, et al. The effects of bromocriptine on preventing postpartum flare in systemic lupus erythematosus patients from South China. J Immunol Res. 2015;2015:316965.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Rigante D, Esposito S. Infections and systemic lupus erythematosus: binding or sparring partners? Int J Mol Sci. 2015;16(8):17331–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ramos-Casals M, Cuadrado MJ, Alba P, et al. Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature. Medicine (Baltimore). 2008;87(6):311–8.

    Article  Google Scholar 

  70. Zhang J, Dou Y, Zhong Z, et al. Clinical characteristics and therapy exploration of active human cytomegalovirus infection in 105 lupus patients. Lupus. 2014;23(9):889–97.

    Article  CAS  PubMed  Google Scholar 

  71. Pothlichet J, Niewold TB, Vitour D, Solhonne B, Crow MK, Si-Tahar M. A loss-of-function variant of the antiviral molecule MAVS is associated with a subset of systemic lupus patients. EMBO Mol Med. 2011;3(3):142–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Balfour HH, Sifakis F, Sliman JA, Knight JA, Schmeling DO, Thomas W. Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition. J Infect Dis. 2013;208(8):1286–93.

    Article  PubMed  Google Scholar 

  73. McClain MT, Heinlen LD, Dennis GJ, Roebuck J, Harley JB, James JA. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat Med. 2005;11(1):85–9.

    Article  CAS  PubMed  Google Scholar 

  74. Arbuckle MR, Reichlin M, Harley JB, James JA. Shared early autoantibody recognition events in the development of anti-Sm B/B’ in human lupus. Scand J Immunol. 1999;50(5):447–55.

    Article  CAS  PubMed  Google Scholar 

  75. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526–33.

    Article  CAS  PubMed  Google Scholar 

  76. Fukuyama S, Kajiwara E, Suzuki N, Miyazaki N, Sadoshima S, Onoyama K. Systemic lupus erythematosus after alpha-interferon therapy for chronic hepatitis C: a case report and review of the literature. Am J Gastroenterol. 2000;95(1):310–2.

    CAS  PubMed  Google Scholar 

  77. Ho V, Mclean A, Terry S. Severe systemic lupus erythematosus induced by antiviral treatment for hepatitis C. J Clin Rheumatol. 2008;14(3):166–8.

    Article  PubMed  Google Scholar 

  78. Rubin RL. Etiology and mechanisms of drug-induced lupus. Curr Opin Rheumatol. 1999;11(5):357–63.

    Article  CAS  PubMed  Google Scholar 

  79. Quddus J, Johnson KJ, Gavalchin J, et al. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest. 1993;92(1):38–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cornacchia E, Golbus J, Maybaum J, Strahler J, Hanash S, Richardson B. Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol. 1988;140(7):2197–200.

    CAS  PubMed  Google Scholar 

  81. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 1990;33(11):1665–73.

    Article  CAS  PubMed  Google Scholar 

  82. Takase K, Horton SC, Ganesha A, et al. What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort. Ann Rheum Dis. 2014;73(9):1695–9.

    Article  CAS  PubMed  Google Scholar 

  83. Araújo-Fernández S, Ahijón-Lana M, Isenberg DA. Drug-induced lupus: including anti-tumour necrosis factor and interferon induced. Lupus. 2014;23(6):545–53.

    Article  PubMed  Google Scholar 

  84. Ramos-Casals M, Brito-Zerón P, Muñoz S, et al. Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore). 2007;86(4):242–51.

    Article  Google Scholar 

  85. Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence, and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991;34(8):937–44.

    Article  CAS  PubMed  Google Scholar 

  86. Petri M, Singh S, Tesfasyone H, Malik A. Prevalence of flare and influence of demographic and serologic factors on flare risk in systemic lupus erythematosus: a prospective study. J Rheumatol. 2009;36(11):2476–80.

    Article  PubMed  Google Scholar 

  87. Gordon C, Sutcliffe N, Skan J, Stoll T, Isenberg DA. Definition and treatment of lupus flares measured by the BILAG index. Rheumatology (Oxford). 2003;42(11):1372–9.

    Article  CAS  Google Scholar 

  88. Nannini C, Crowson CS, Matteson EL, Moder KG. Mycophenolate mofetil is effective in reducing disease flares in systemic lupus erythematosus patients: a retrospective study. Lupus. 2009;18(5):394–9.

    Article  CAS  PubMed  Google Scholar 

  89. Nikpour M, Urowitz MB, Ibañez D, Gladman DD. Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus. Arthritis Rheum. 2009;61(9):1152–8.

    Article  PubMed  Google Scholar 

  90. Nossent J, Kiss E, Rozman B, et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus. 2010;19(8):949–56.

    Article  CAS  PubMed  Google Scholar 

  91. Kalunian KC, Merrill JT, Maciuca R, et al. A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis. 2016;75(1):196–202.

    Article  PubMed  Google Scholar 

  92. Costedoat-Chalumeau N, Galicier L, Aumaître O, et al. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS study). Ann Rheum Dis. 2013;72(11):1786–92.

    Article  CAS  PubMed  Google Scholar 

  93. Merrill JT, Burgos-Vargas R, Westhovens R, et al. The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62(10):3077–87.

    Article  CAS  PubMed  Google Scholar 

  94. Isenberg D, Gordon C, Licu D, Copt S, Rossi CP, Wofsy D. Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial). Ann Rheum Dis. 2015;74(11):2006–15.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Merrill J, Buyon J, Furie R, et al. Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER). Lupus. 2011;20(7):709–16.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Kyriakos A. Kirou.

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Fernandez, D., Kirou, K.A. What Causes Lupus Flares?. Curr Rheumatol Rep 18, 14 (2016). https://doi.org/10.1007/s11926-016-0562-3

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