Systemic Lupus Erythematosus (SLE) Medication: Antimalarials, NSAIDs, DMARDS, Immunomodulators, Rheumatologics, Other, Corticosteroids, DMARDs, Other, Interferon Antagonists, Calcineurin Inhibitors, Calcineurin Inhibitors (original) (raw)

Medication Summary

Treatment of systemic lupus erythematosus (SLE) is guided by the individual patient's manifestations. Fever, rash, musculoskeletal manifestations, and serositis generally respond to treatment with hydroxychloroquine (HCQ), nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids in low to moderate doses, as necessary, for acute flares. Medications such as methotrexate may be useful in chronic lupus arthritis, and azathioprine and mycophenolate have been widely used in lupus of moderate severity. [198]

Central nervous system or kidney involvement constitutes more serious disease and often requires high-dose steroids and other immunosuppressive agents, such as cyclophosphamide, azathioprine, or mycophenolate. Class IV diffuse proliferative lupus nephritis has also been treated with aggressive cyclophosphamide induction therapy. [199, 200] Trials of mycophenolate induction therapy have also demonstrated efficacy, particularly in Black patients. [201, 202, 203] Rituximab trials have not documented a benefit overall, but this agent continues to be used for treatment of severe SLE that is refractory to standard therapy. [153, 154] For lupus nephritis maintenance therapy, mycophenolate is generally preferred, but azathioprine is an alternative. [170]

Newer agents for treatment of SLE are the B-lymphocyte inhibitor belimumab, the interferon antagonist anifrolumab, and the calcineurin inhibitor voclosporin.

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Antimalarials

Class Summary

Antimalarial agents may work through numerous proposed mechanisms in SLE, mediating subtle immunomodulation without causing overt immunosuppression. These drugs are useful in preventing and treating lupus skin rashes, constitutional symptoms, arthralgias, and arthritis; antimalarials also help to prevent lupus flares and have been associated with reduced morbidity and mortality in SLE patients followed in observational trials. [118]

Hydroxychloroquine sulfate (Plaquenil)

Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate. Weight-based dose adjustment and monitoring help to mitigate the risk of retinal toxicity. This agent is also commonly used for suppression and treatment of malaria.

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NSAIDs

Class Summary

Nonsteroidal anti-inflammatory agents (NSAIDS) provide symptomatic relief for arthralgias, fever, headache, and mild serositis. NSAIDs may cause elevated creatinine or liver function test results in patients with active systemic lupus erythematosus. Additionally, concomitant administration with prednisone may increase the risk of gastrointestinal ulceration.

Ibuprofen (Advil, Motrin)

Ibuprofen is the drug of choice for patients with mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Aleve, Anaprox, Naprosyn)

Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of the enzyme cyclooxygenase, resulting in prostaglandin synthesis.

Diclofenac (Voltaren XR, Cataflam)

Diclofenac inhibits prostaglandin synthesis by decreasing activity of enzyme cyclo-oxygenase, which in turn decreases formation of prostaglandin precursors.

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DMARDS, Immunomodulators

Class Summary

Disease-modifying antirheumatic drugs (DMARDS) are immunomodulatory agents that act as immunosuppressives and cytotoxic and anti-inflammatory medications. The specific agent selection is generally indicated by the patient’s organ involvement and disease severity. Due to toxicity, cyclophosphamide is reserved for severe organ-threatening disease. At the other end of the spectrum, methotrexate or azathioprine may be helpful for milder arthritis or skin disease. DMARDS can be used in patients whose condition has had an inadequate response to glucocorticoids. Azathioprine, mycophenolate, and cyclosporine have all been studied for lupus manifestations such as nephritis.

Cyclophosphamide

Cyclophosphamide is used for immunosuppression in cases of serious SLE organ involvement, especially severe CNS involvement, vasculitis, and lupus nephritis. This agent is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Methotrexate (Otrexup, Rasuvo)

Methotrexate is used for managing arthritis, serositis, cutaneous, and constitutional symptoms. It blocks purine synthesis and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Methotrexate ameliorates symptoms of inflammation and is particularly useful in arthritis treatment.

Azathioprine (Imuran, Azasan)

Azathioprine is an immunosuppressant and a less toxic alternative to cyclophosphamide. It is used as a steroid-sparing agent in nonrenal disease. Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity.

Mycophenolate (CellCept, Myfortic)

Mycophenolate is useful for maintenance in lupus nephritis and other serious lupus cases. This agent inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Mycophenolate also inhibits antibody production.

Immune globulin IV (IGIV) (Bivigam, Carimune, Gammagard S/D, Flebogamma, Gamunex-C)

Intravenous immune globulin is used for immunosuppression in serious SLE flares. It neutralizes circulating myelin antibodies through anti-idiotypic antibodies. This agent downregulates proinflammatory cytokines, including interferon-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells; and augments suppressor T cells. Immune globulin also blocks complement cascade, promotes remyelination, and may increase cerebrospinal fluid IgG (10%).

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Rheumatologics, Other

Class Summary

Rheumatologic agents such belimumab reduce immune response and B-cell mediated immunity.

Belimumab (Benlysta)

Belimumab inhibits the biologic activity of B-lymphocyte stimulator (BLyS); BLyS is a naturally occurring protein required for survival and for development of B-lymphocyte cells into mature plasma B cells that produce antibodies. In autoimmune diseases, elevated BLyS levels are thought to contribute to production of autoantibodies.

This agent is indicated for active, autoantibody-positive SLE that is refractory to standard therapy including hydroxychloroquine (see Treatment for more details).

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Corticosteroids

Class Summary

Corticosteroid agents are used predominantly for anti-inflammatory activity and as immunosuppressants. Preparations include oral, intravenous, topical, and intra-articular injections.

Methylprednisolone (A-Methapred, Medrol, Solu-Medrol, Depo-Medrol)

Methylprednisolone is used for acute organ-threatening exacerbations. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Prednisone

Prednisone is an immunosuppressant for treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Low-dose oral prednisone can be used for milder SLE, but more severe involvement necessitates high doses of oral or intravenous therapy.

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DMARDs, Other

Class Summary

Rituximab is a monoclonal antibody and an immunosuppressant that eliminates mature circulating B-cells.

Rituximab (Rituxan)

B-cell depletion with rituximab has been used successfully for rheumatoid arthritis, but it has shown mixed results for the treatment of SLE. One open study using rituximab reported excellent results as rescue therapy for patients with active SLE who were unresponsive to standard immunosuppressant therapy. However, 2 large placebo-controlled studies failed to show an overall significant response. Note that rituximab has an off-label indication for SLE.

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Interferon Antagonists

Anifrolumab (Anifrolumab-fnia, Saphnelo)

Anifrolumab is a human monoclonal antibody to type I interferon receptor subunit 1 that suppresses interferon gene signatures and substantially reduced SLE disease activity. It is indicated for the treatment of moderate-to-severe SLE.

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Calcineurin Inhibitors

Tacrolimus and Voclosporin

Calcineurin inhibitors (CNIs) are medicines which inhibit the action of calcineurin. Calcineurin is an enzyme that activates T-cells of the immune system. T-lymphocytes are a type of white blood cell that play a key role in cell-mediated immunity. Tacrolimus abd volcosporin are two common CNIs used in patients with lupus nephritis. Tacrolimus needs trough level monitoring and dose is adjusted to achieve a target level of 6-8, while volcosporin does not need trough level monitoring and standard dose of 23.7 mg twice daily is given.

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Calcineurin Inhibitors

Voclosporin (Lupkynis)

FDA approved calcineurin-inhibitor immunosuppressant indicated for active lupus nephritis, in combination with a background immunosuppressive therapy regimen. Activation of lymphocytes involves an increase in intracellular calcium concentrations that bind to calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation activates the transcription factor, Nuclear Factor of Activated T-Cell Cytoplasmic

Immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens

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  1. Siegel CH, Sammaritano LR. Systemic Lupus Erythematosus: A Review. JAMA. 2024 May 7. 331 (17):1480-1491. [QxMD MEDLINE Link].
  2. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019 Sep. 78 (9):1151-1159. [QxMD MEDLINE Link].
  3. Dall'Era M, Wofsy D. Clinical Manifestations of Systemic Lupus Erythematosus. Firestein GS, Budd RC, Gabriel SE, MacInnes IB, O’Dell JR, eds. Kelley and Firestein's Textbook of Rheumatology. 10th ed. Philadelphia, Pa: Elsevier Saunders; 2017. 1345-67.
  4. Huang X, Jia N, Xiao F, Sun C, Zhu J, Lai J, et al. Differences in the Clinical Manifestations and Mortality of Systemic Lupus Erythematosus Onset in Children and Adults: A Systematic Review and Meta-Analysis. Int Arch Allergy Immunol. 2022. 183 (1):116-126. [QxMD MEDLINE Link].
  5. American College of Rheumatology. 1997 Update of the 1982 American College of Rheumatology revised criteria for classification of systemic lupus erythematosus. Available at https://www.rheumatology.org/Portals/0/Files/1997%20Update%20of%201982%20Revised.pdf. Accessed: August 4, 2021.
  6. Bertsias G, Fanouriakis A, Boumpas DT. Treatment of Systemic Lupus Erythematosus. Firestein GS, Budd RC, Gabriel SE, MacInnes IB, O’Dell JR, eds. Kelley and Firestein's Textbook of Rheumatology. 10th ed. Philadelphia, Pa: Elsevier Saunders; 2017. 1368-88.
  7. Cooper GS, Dooley MA, Treadwell EL, St Clair EW, Parks CG, Gilkeson GS. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. Arthritis Rheum. 1998 Oct. 41(10):1714-24. [QxMD MEDLINE Link].
  8. Lupus Foundation of America. What causes lupus?. Available at https://www.lupus.org/resources/what-causes-lupus. November 28, 2016; Accessed: June 15, 2022.
  9. Kwon YC, Chun S, Kim K, Mak A. Update on the Genetics of Systemic Lupus Erythematosus: Genome-Wide Association Studies and Beyond. Cells. 2019 Sep 30. 8 (10):[QxMD MEDLINE Link].
  10. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003 Oct 16. 349(16):1526-33. [QxMD MEDLINE Link].
  11. Andrade F, Casciola-Rosen L, Rosen A. Apoptosis in systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am. 2000 May. 26(2):215-27, v. [QxMD MEDLINE Link].
  12. Crow MK. Etiology and Pathogenesis of Systemic Lupus Erythematosus. Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR, eds. Kelley and Firestein's Textbook of Rheumatology. 10th ed. Philadelphia, Pa: Elsevier Saunders; 2017. 1329-44.
  13. Munoz LE, Gaipl US, Franz S, Sheriff A, Voll RE, Kalden JR, et al. SLE--a disease of clearance deficiency?. Rheumatology (Oxford). 2005 Sep. 44(9):1101-7. [QxMD MEDLINE Link].
  14. Muñoz LE, Janko C, Grossmayer GE, et al. Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus. Arthritis Rheum. 2009 Jun. 60(6):1733-42. [QxMD MEDLINE Link].
  15. Cancro MP, D'Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest. 2009 May. 119(5):1066-73. [QxMD MEDLINE Link]. [Full Text].
  16. Lo MS, Tsokos GC. T cells in systemic lupus erythematosus: progress toward targeted therapy [August 2011]. The Rheumatologist. [Full Text].
  17. Hanly JG, Urowitz MB, Su L, et al. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis. 2011 Oct. 70(10):1726-32. [QxMD MEDLINE Link].
  18. Jia J, Xie J, Li H, Wei H, Li X, Hu J, et al. Cerebral blood flow abnormalities in neuropsychiatric systemic lupus erythematosus. Lupus. 2019 Jul 18. 961203319861677. [QxMD MEDLINE Link].
  19. Bosch X. Systemic lupus erythematosus and the neutrophil. N Engl J Med. 2011 Aug 25. 365(8):758-60. [QxMD MEDLINE Link].
  20. Carmona-Fernandes D, Santos MJ, Canhão H, Fonseca JE. Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus erythematosus: diagnostic performance and clinical profile. BMC Med. 2013 Apr 4. 11:98. [QxMD MEDLINE Link]. [Full Text].
  21. Deng Y, Tsao BP. Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol. 2010 Dec. 6(12):683-92. [QxMD MEDLINE Link]. [Full Text].
  22. Tusseau M, Khaldi-Plassart S, Cognard J, Viel S, Khoryati L, Benezech S, et al. Mendelian Causes of Autoimmunity: the Lupus Phenotype. J Clin Immunol. 2024 Apr 15. 44 (4):99. [QxMD MEDLINE Link].
  23. Ulff-Møller CJ, Simonsen J, Kyvik KO, Jacobsen S, Frisch M. Family history of systemic lupus erythematosus and risk of autoimmune disease: Nationwide Cohort Study in Denmark 1977-2013. Rheumatology (Oxford). 2017 Jun 1. 56 (6):957-964. [QxMD MEDLINE Link]. [Full Text].
  24. Kuo CF, Grainge MJ, Valdes AM, See LC, Luo SF, Yu KH, et al. Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families. JAMA Intern Med. 2015 Sep. 175 (9):1518-26. [QxMD MEDLINE Link]. [Full Text].
  25. Sestak AL, Fürnrohr BG, Harley JB, Merrill JT, Namjou B. The genetics of systemic lupus erythematosus and implications for targeted therapy. Ann Rheum Dis. 2011 Mar. 70 Suppl 1:i37-43. [QxMD MEDLINE Link].
  26. Sanchez E, Nadig A, Richardson BC, et al. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis. 2011 Oct. 70(10):1752-7. [QxMD MEDLINE Link].
  27. Järvinen TM, Hellquist A, Zucchelli M, et al. Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population. Rheumatology (Oxford). 2012 Jan. 51(1):87-92. [QxMD MEDLINE Link].
  28. Hu W, Ren H. A meta-analysis of the association of IRF5 polymorphism with systemic lupus erythematosus. Int J Immunogenet. 2011 Oct. 38(5):411-7. [QxMD MEDLINE Link].
  29. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011 Dec 1. 365(22):2110-21. [QxMD MEDLINE Link].
  30. Lanata CM, Chung SA, Criswell LA. DNA methylation 101: what is important to know about DNA methylation and its role in SLE risk and disease heterogeneity. Lupus Sci Med. 2018. 5 (1):e000285. [QxMD MEDLINE Link]. [Full Text].
  31. Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol. 2018 Jan 26. 3 (19):[QxMD MEDLINE Link].
  32. Brown GJ, Cañete PF, Wang H, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022 Apr 27. [QxMD MEDLINE Link].
  33. Pyfrom S, Paneru B, Knox JJ, Cancro MP, Posso S, Buckner JH, et al. The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients. Proc Natl Acad Sci U S A. 2021 Jun 15. 118 (24):[QxMD MEDLINE Link]. [Full Text].
  34. Joo YB, Lim J, Tsao BP, Nath SK, Kim K, Bae SC. Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort. Sci Rep. 2018 Jul 2. 8 (1):9962. [QxMD MEDLINE Link].
  35. Morris DL, Sheng Y, Zhang Y, Wang YF, Zhu Z, Tombleson P, et al. Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus. Nat Genet. 2016 Aug. 48 (8):940-946. [QxMD MEDLINE Link].
  36. Blank M, Shoenfeld Y, Perl A. Cross-talk of the environment with the host genome and the immune system through endogenous retroviruses in systemic lupus erythematosus. Lupus. 2009 Nov. 18(13):1136-43. [QxMD MEDLINE Link].
  37. Tsokos GC, Magrath IT, Balow JE. Epstein-Barr virus induces normal B cell responses but defective suppressor T cell responses in patients with systemic lupus erythematosus. J Immunol. 1983 Oct. 131(4):1797-801. [QxMD MEDLINE Link].
  38. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018 Mar 9. 359 (6380):1156-1161. [QxMD MEDLINE Link]. [Full Text].
  39. Buyon JP, Kim MY, Salmon JE. Predictors of Pregnancy Outcomes in Patients With Lupus. Ann Intern Med. 2016 Jan 19. 164 (2):131. [QxMD MEDLINE Link].
  40. Athanassiou L, Kostoglou-Athanassiou I, Koutsilieris M, Shoenfeld Y. Vitamin D and Autoimmune Rheumatic Diseases. Biomolecules. 2023 Apr 21. 13 (4):184-91. [QxMD MEDLINE Link]. [Full Text].
  41. Young KA, Munroe ME, Guthridge JM, Kamen DL, Niewold TB, Gilkeson GS, et al. Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus. Ann Rheum Dis. 2016 Jun 9. [QxMD MEDLINE Link].
  42. Hu W, Niu G, Lin Y, Chen X, Lin L. Impact of the polymorphism in vitamin D receptor gene BsmI and the risk of systemic lupus erythematosus: an updated meta-analysis. Clin Rheumatol. 2016 Apr. 35 (4):927-34. [QxMD MEDLINE Link].
  43. Lehmann P, Hölzle E, Kind P, Goerz G, Plewig G. Experimental reproduction of skin lesions in lupus erythematosus by UVA and UVB radiation. J Am Acad Dermatol. 1990 Feb. 22(2 Pt 1):181-7. [QxMD MEDLINE Link].
  44. Parks CG, D'Aloisio AA, Sandler DP. Early Life Factors Associated with Adult-Onset Systemic Lupus Erythematosus in Women. Front Immunol. 2016. 7:103. [QxMD MEDLINE Link]. [Full Text].
  45. Izmirly PM, Ferucci ED, Somers EC, Wang L, Lim SS, Drenkard C, et al. Incidence rates of systemic lupus erythematosus in the USA: estimates from a meta-analysis of the Centers for Disease Control and Prevention national lupus registries. Lupus Sci Med. 2021 Dec. 8 (1):[QxMD MEDLINE Link]. [Full Text].
  46. Understanding Lupus. Lupus Foundation of America. Available at https://www.lupus.org/understanding-lupus-0. 2024; Accessed: August 15, 2024.
  47. Singh RR, Yen EY. SLE mortality remains disproportionately high, despite improvements over the last decade. Lupus. 2018 Sep. 27 (10):1577-1581. [QxMD MEDLINE Link].
  48. Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, Jansen-McWilliams L, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997 Mar 1. 145 (5):408-15. [QxMD MEDLINE Link].
  49. Yen EY, Singh RR. Brief Report: Lupus-An Unrecognized Leading Cause of Death in Young Females: A Population-Based Study Using Nationwide Death Certificates, 2000-2015. Arthritis Rheumatol. 2018 Aug. 70 (8):1251-1255. [QxMD MEDLINE Link].
  50. Garg S, Bartels CM, Bao G, Helmick CG, Drenkard C, Lim SS. Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities. J Rheumatol. 2022 Aug 1. [QxMD MEDLINE Link].
  51. Lim SS, Helmick CG, Bao G, Hootman J, Bayakly R, Gordon C, et al. Racial Disparities in Mortality Associated with Systemic Lupus Erythematosus - Fulton and DeKalb Counties, Georgia, 2002-2016. MMWR Morb Mortal Wkly Rep. 2019 May 10. 68 (18):419-422. [QxMD MEDLINE Link].
  52. Gianfrancesco MA, Dall'Era M, Murphy LB, Helmick CG, Li J, Rush S, et al. Mortality Among Minority Populations with Systemic Lupus Erythematosus, Including Asian and Hispanic/Latino Persons - California, 2007-2017. MMWR Morb Mortal Wkly Rep. 2021 Feb 19. 70 (7):236-239. [QxMD MEDLINE Link].
  53. Tian J, Zhang D, Yao X, Huang Y, Lu Q. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023 Mar. 82 (3):351-356. [QxMD MEDLINE Link]. [Full Text].
  54. Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus. 2006. 15(5):308-18. [QxMD MEDLINE Link].
  55. Symmons DP. Frequency of lupus in people of African origin. Lupus. 1995 Jun. 4(3):176-8. [QxMD MEDLINE Link].
  56. Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken). 2012 Feb. 64(2):159-68. [QxMD MEDLINE Link].
  57. Lupus. American College of Rheumatology. Available at https://rheumatology.org/patients/lupus. February 2023; Accessed: August 15, 2024.
  58. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007 Apr. 56(4):1251-62. [QxMD MEDLINE Link].
  59. Dillon S, Aggarwal R, Harding JW, et al. Klinefelter's syndrome (47,XXY) among men with systemic lupus erythematosus. Acta Paediatr. 2011 Jun. 100(6):819-23. [QxMD MEDLINE Link].
  60. Manzi S. Epidemiology of systemic lupus erythematosus. Am J Manag Care. 2001 Oct. 7(16 Suppl):S474-9. [QxMD MEDLINE Link].
  61. Klein-Gitelman M, Reiff A, Silverman ED. Systemic lupus erythematosus in childhood. Rheum Dis Clin North Am. 2002 Aug. 28(3):561-77, vi-vii. [QxMD MEDLINE Link].
  62. Pineles D, Valente A, Warren B, Peterson MG, Lehman TJ, Moorthy LN. Worldwide incidence and prevalence of pediatric onset systemic lupus erythematosus. Lupus. 2011 Oct. 20(11):1187-92. [QxMD MEDLINE Link].
  63. Boddaert J, Huong DL, Amoura Z, Wechsler B, Godeau P, Piette JC. Late-onset systemic lupus erythematosus: a personal series of 47 patients and pooled analysis of 714 cases in the literature. Medicine (Baltimore). 2004 Nov. 83(6):348-59. [QxMD MEDLINE Link].
  64. Faurschou M, Dreyer L, Kamper AL, Starklint H, Jacobsen S. Long-term mortality and renal outcome in a cohort of 100 patients with lupus nephritis. Arthritis Care Res (Hoboken). 2010 Jun. 62(6):873-80. [QxMD MEDLINE Link].
  65. Kasitanon N, Magder LS, Petri M. Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore). 2006 May. 85(3):147-56. [QxMD MEDLINE Link].
  66. Urowitz MB, Gladman DD, Ibañez D, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res (Hoboken). 2012 Jan. 64(1):132-7. [QxMD MEDLINE Link].
  67. [Guideline] Bertsias G, et al; Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis. 2008 Feb. 67 (2):195-205. [QxMD MEDLINE Link]. [Full Text].
  68. Ruiz-Irastorza G, Khamashta MA, Castellino G, Hughes GR. Systemic lupus erythematosus. Lancet. 2001 Mar 31. 357(9261):1027-32. [QxMD MEDLINE Link].
  69. Trager J, Ward MM. Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol. 2001 Sep. 13(5):345-51. [QxMD MEDLINE Link].
  70. Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality. J Rheumatol. 1995 Jul. 22(7):1265-70. [QxMD MEDLINE Link].
  71. Li D, Yoshida K, Feldman CH, Speyer C, Barbhaiya M, Guan H, et al. Initial disease severity, cardiovascular events and all-cause mortality among patients with systemic lupus erythematosus. Rheumatology (Oxford). 2019 Jul 18. [QxMD MEDLINE Link].
  72. Murali R, Jeyaseelan L, Rajaratnam S, John L, Ganesh A. Systemic lupus erythematosus in Indian patients: prognosis, survival and life expectancy. Natl Med J India. 1997 Jul-Aug. 10(4):159-64. [QxMD MEDLINE Link].
  73. Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus. 1997. 6(3):248-53. [QxMD MEDLINE Link].
  74. Centers for Disease Control and Prevention. Systemic lupus erythematosus (SLE). Available at https://www.cdc.gov/lupus/facts/detailed.html. October 17, 2018; Accessed: August 4, 2021.
  75. [Guideline] Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun. 78 (6):736-745. [QxMD MEDLINE Link]. [Full Text].
  76. Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med. 1976 Feb. 60(2):221-5. [QxMD MEDLINE Link].
  77. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore). 1999 May. 78(3):167-75. [QxMD MEDLINE Link].
  78. Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, Jansen-McWilliams L, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997 Mar 1. 145(5):408-15. [QxMD MEDLINE Link].
  79. Gladman DD, Urowitz MB. Prognosis, mortality and morbidity in systemic lupus erythematosus In: Wallace DJ, Hahn BH. Dubois’ lupus erythematosus. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2007:1333-53.
  80. Faurschou M, Mellemkjaer L, Starklint H, et al. High risk of ischemic heart disease in patients with lupus nephritis. J Rheumatol. 2011 Nov. 38(11):2400-5. [QxMD MEDLINE Link].
  81. Petri M, Spence D, Bone LR, Hochberg MC. Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices. Medicine (Baltimore). 1992 Sep. 71(5):291-302. [QxMD MEDLINE Link].
  82. Salmon JE, Roman MJ. Accelerated atherosclerosis in systemic lupus erythematosus: implications for patient management. Curr Opin Rheumatol. 2001 Sep. 13(5):341-4. [QxMD MEDLINE Link].
  83. Alarcón GS, McGwin G Jr, Bastian HM, Roseman J, Lisse J, Fessler BJ, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum. 2001 Apr. 45(2):191-202. [QxMD MEDLINE Link].
  84. Somers EC, Marder W, Cagnoli P, Lewis EE, DeGuire P, Gordon C, et al. Population-based incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program. Arthritis Rheumatol. 2014 Feb. 66 (2):369-78. [QxMD MEDLINE Link]. [Full Text].
  85. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Sep. 71 (9):1400-1412. [QxMD MEDLINE Link].
  86. Wojdyla D, Pons-Estel GJ, Quintana R, et al. Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort. Lupus. 2019 Jul 10. 961203319860579. [QxMD MEDLINE Link].
  87. Oinuma K, Harada Y, Nawata Y, Takabayashi K, Abe I, Kamikawa K, et al. Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Ann Rheum Dis. 2001 Dec. 60(12):1145-8. [QxMD MEDLINE Link]. [Full Text].
  88. Gladman DD, Urowitz MB, Chaudhry-Ahluwalia V, Hallet DC, Cook RJ. Predictive factors for symptomatic osteonecrosis in patients with systemic lupus erythematosus. J Rheumatol. 2001 Apr. 28(4):761-5. [QxMD MEDLINE Link].
  89. Firestein GS, Budd RC, Harris ED Jr, et al, eds. Kelley's Textbook of Rheumatology. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2008.
  90. Callen JP. Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus. Clinical and laboratory findings in seventeen patients. J Am Acad Dermatol. 1985 Feb. 12(2 Pt 1):278-88. [QxMD MEDLINE Link].
  91. Healy E, Kieran E, Rogers S. Cutaneous lupus erythematosus--a study of clinical and laboratory prognostic factors in 65 patients. Ir J Med Sci. 1995 Apr-Jun. 164(2):113-5. [QxMD MEDLINE Link].
  92. Wallace D, Edmund D, eds. Dubois' Lupus Erythematosus. Philadelphia, Pa: Lippincott Williams & Wilkins.; 2006.
  93. Jennekens FG, Kater L. The central nervous system in systemic lupus erythematosus. Part 1. Clinical syndromes: a literature investigation. Rheumatology (Oxford). 2002 Jun. 41(6):605-18. [QxMD MEDLINE Link].
  94. Jennekens FG, Kater L. The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic mechanisms of clinical syndromes: a literature investigation. Rheumatology (Oxford). 2002 Jun. 41(6):619-30. [QxMD MEDLINE Link].
  95. Bertsias GK, Ioannidis JP, Aringer M, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis. 2010 Dec. 69(12):2074-82. [QxMD MEDLINE Link].
  96. American College of Rheumatology. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999 Apr. 42 (4):599-608. [QxMD MEDLINE Link].
  97. Varaprasad IR, Agrawal S, Prabu VN, Rajasekhar L, Kanikannan MA, Narsimulu G. Posterior reversible encephalopathy syndrome in systemic lupus erythematosus. J Rheumatol. 2011 Aug. 38(8):1607-11. [QxMD MEDLINE Link].
  98. Petri M, Naqibuddin M, Carson KA, Wallace DJ, Weisman MH, Holliday SL, et al. Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus. J Rheumatol. 2010 Oct. 37(10):2032-8. [QxMD MEDLINE Link].
  99. Messer J, Reitman D, Sacks HS, Smith H Jr, Chalmers TC. Association of adrenocorticosteroid therapy and peptic-ulcer disease. N Engl J Med. 1983 Jul 7. 309(1):21-4. [QxMD MEDLINE Link].
  100. Luís M, Brites AL, Duarte AC, Teixeira V, Freitas R, Oliveira-Ramos F, et al. How to diagnose lupus enteritis early? Lessons learned from a multicenter case series. Acta Reumatol Port. 2019 Jun 2. [QxMD MEDLINE Link].
  101. Nodler J, Moolamalla SR, Ledger EM, Nuwayhid BS, Mulla ZD. Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset. BMC Pregnancy Childbirth. 2009 Mar 16. 9:11. [QxMD MEDLINE Link]. [Full Text].
  102. Ramos-Casals M, Cuadrado MJ, Alba P, Sanna G, Brito-Zerón P, Bertolaccini L, et al. Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature. Medicine (Baltimore). 2008 Nov. 87(6):311-8. [QxMD MEDLINE Link].
  103. Fessler BJ. Infectious diseases in systemic lupus erythematosus: risk factors, management and prophylaxis. Best Pract Res Clin Rheumatol. 2002 Apr. 16(2):281-91. [QxMD MEDLINE Link].
  104. Stefanidou S, Benos A, Galanopoulou V, et al. Clinical expression and morbidity of systemic lupus erythematosus during a post-diagnostic 5-year follow-up: a male:female comparison. Lupus. 2011 Oct. 20(10):1090-4. [QxMD MEDLINE Link].
  105. Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus in children and adults. Neurol Clin. 2010 Feb. 28(1):61-73. [QxMD MEDLINE Link]. [Full Text].
  106. Lin YC, Wang AG, Yen MY. Systemic lupus erythematosus-associated optic neuritis: clinical experience and literature review. Acta Ophthalmol. 2009 Mar. 87(2):204-10. [QxMD MEDLINE Link].
  107. Williams EL, Gadola S, Edwards CJ. Anti-TNF-induced lupus. Rheumatology (Oxford). 2009 Jul. 48(7):716-20. [QxMD MEDLINE Link].
  108. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug. 64(8):2677-86. [QxMD MEDLINE Link]. [Full Text].
  109. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012 Jun. 64(6):797-808. [QxMD MEDLINE Link]. [Full Text].
  110. Elkon KB. Systemic lupus erythematosus: autoantibodies in SLE. In: Klippel JH, Dieppe PA, eds. Rheumatology. 2nd ed. St. Louis, Mo: Mosby; 1998:
  111. Hanly JG, Urowitz MB, Su L, et al. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis. 2011 Oct. 70(10):1726-32. [QxMD MEDLINE Link].
  112. FDA Clears Thermo Scientific EliA RNA Pol III and EliA Rib-P Tests for Use in U.S. Thermo Fisher Scientific. Available at https://corporate.thermofisher.com/content/tfcorpsite/us/en/index/newsroom/press-releases/2022/Jun/09-FDA-Clears-Thermo-Scientific-EliA-RNA-Pol-III-and-EliA-Rib-P-Tests-for-Use-in-US.html. June 9, 2022; Accessed: June 15, 2022.
  113. Czeizel A. A case-control analysis of the teratogenic effects of co-trimoxazole. Reprod Toxicol. 1990. 4(4):305-13. [QxMD MEDLINE Link].
  114. Mavrogeni S, Bratis K, Markussis V, Spargias C, et al. The diagnostic role of cardiac magnetic resonance imaging in detecting myocardial inflammation in systemic lupus erythematosus. Differentiation from viral myocarditis. Lupus. 2013. 22(1):34-43. [QxMD MEDLINE Link].
  115. Hwang J, Kim HJ, Oh JM, et al. Outcome of reclassification of World Health Organization (WHO) class III under International Society of Nephrology-Renal Pathology Society (ISN-RPS) classification: retrospective observational study. Rheumatol Int. 2012 Jul. 32(7):1877-84. [QxMD MEDLINE Link].
  116. Mittal B, Hurwitz S, Rennke H, Singh AK. New subcategories of class IV lupus nephritis: are there clinical, histologic, and outcome differences?. Am J Kidney Dis. 2004 Dec. 44(6):1050-9. [QxMD MEDLINE Link].
  117. Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. Feb 2004;15(2):241-50:[QxMD MEDLINE Link].
  118. Alarcón GS, McGwin G, Bertoli AM, Fessler BJ, Calvo-Alén J, Bastian HM, et al. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis. 2007 Sep. 66(9):1168-72. [QxMD MEDLINE Link]. [Full Text].
  119. Broder A, Khattri S, Patel R, Putterman C. Undertreatment of Disease Activity in Systemic Lupus Erythematosus Patients with Endstage Renal Failure Is Associated with Increased All-cause Mortality. J Rheumatol. 2011 Nov. 38(11):2382-9. [QxMD MEDLINE Link].
  120. Mikdashi J, Nived O. Measuring disease activity in adults with systemic lupus erythematosus: the challenges of administrative burden and responsiveness to patient concerns in clinical research. Arthritis Res Ther. 2015 Jul 20. 17:183. [QxMD MEDLINE Link]. [Full Text].
  121. Zucchi D, Elefante E, Schilirò D, Signorini V, Trentin F, Bortoluzzi A, et al. One year in review 2022: systemic lupus erythematosus. Clin Exp Rheumatol. 2022 Jan. 40 (1):4-14. [QxMD MEDLINE Link]. [Full Text].
  122. Jesus D, Larosa M, Henriques C, Matos A, Zen M, Tomé P, et al. Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity. Ann Rheum Dis. 2021 Dec. 80 (12):1568-1574. [QxMD MEDLINE Link]. [Full Text].
  123. Furie RA, Petri MA, Wallace DJ, et al. Novel evidence-based systemic lupus erythematosus responder index. Arthritis Rheum. 2009 Sep 15. 61(9):1143-51. [QxMD MEDLINE Link]. [Full Text].
  124. Yazdany J, Panopalis P, Gillis JZ, Schmajuk G, MacLean CH, Wofsy D, et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum. 2009 Mar 15. 61(3):370-7. [QxMD MEDLINE Link]. [Full Text].
  125. [Guideline] Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Feb 23. [QxMD MEDLINE Link]. [Full Text].
  126. Zheng ZH, Gao CC, Wu ZZ, Liu SY, Li TF, Gao GM, et al. High prevalence of hypovitaminosis D of patients with autoimmune rheumatic diseases in China. Am J Clin Exp Immunol. 2016. 5 (3):48-54. [QxMD MEDLINE Link]. [Full Text].
  127. Salman-Monte TC, Torrente-Segarra V, Almirall M, Corzo P, Mojal S, Carbonell-Abelló J. Prevalence and predictors of vitamin D insufficiency in supplemented and non-supplemented women with systemic lupus erythematosus in the Mediterranean region. Rheumatol Int. 2016 Jul. 36 (7):975-85. [QxMD MEDLINE Link].
  128. Lima GL, Paupitz J, Aikawa NE, Takayama L, Bonfa E, Pereira RM. Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2016 Jan. 68 (1):91-8. [QxMD MEDLINE Link].
  129. Reynolds J, Ray D, Alexander MY, Bruce I. Role of vitamin D in endothelial function and endothelial repair in clinically stable systemic lupus erythematosus. Lancet. 2015 Feb 26. 385 Suppl 1:S83. [QxMD MEDLINE Link].
  130. Kamen DL, Oates JC. A Pilot Randomized Controlled Trial of Vitamin D Repletion to Determine if Endothelial Function Improves in Patients With Systemic Lupus Erythematosus. Am J Med Sci. 2015 Sep 7. [QxMD MEDLINE Link].
  131. Reynolds JA, Haque S, Williamson K, Ray DW, Alexander MY, Bruce IN. Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus. Sci Rep. 2016 Mar 1. 6:22341. [QxMD MEDLINE Link].
  132. Almeida-Brasil CC, Hanly JG, Urowitz M, Clarke AE, Ruiz-Irastorza G, Gordon C, et al. Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Ann Rheum Dis. 2022 Mar. 81 (3):370-378. [QxMD MEDLINE Link].
  133. Toloza SM, Roseman JM, Alarcón GS, McGwin G Jr, Uribe AG, Fessler BJ, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage. Arthritis Rheum. 2004 Oct. 50 (10):3177-86. [QxMD MEDLINE Link].
  134. Fessler BJ, Alarcón GS, McGwin G Jr, Roseman J, Bastian HM, Friedman AW, et al. Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum. 2005 May. 52 (5):1473-80. [QxMD MEDLINE Link].
  135. Petri M, Konig MF, Li J, Goldman DW. Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021 Jun. 73 (6):997-1004. [QxMD MEDLINE Link].
  136. Fasano S, Pierro L, Pantano I, Iudici M, Valentini G. 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. J Rheumatol. 2017 Jul. 44 (7):1032-1038. [QxMD MEDLINE Link].
  137. Costedoat-Chalumeau N, Dunogué B, Morel N, Le Guern V, Guettrot-Imbert G. Hydroxychloroquine: a multifaceted treatment in lupus. Presse Med. 2014 Jun. 43 (6 Pt 2):e167-80. [QxMD MEDLINE Link].
  138. Levy RA, Vilela VS, Cataldo MJ, Ramos RC, Duarte JL, Tura BR, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus. 2001. 10 (6):401-4. [QxMD MEDLINE Link].
  139. Izmirly PM, Kim MY, Llanos C, Le PU, Guerra MM, Askanase AD, et al. Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis. 2010 Oct. 69 (10):1827-30. [QxMD MEDLINE Link].
  140. Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Apr. 72 (4):529-556. [QxMD MEDLINE Link].
  141. Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26. 377(9767):721-31. [QxMD MEDLINE Link].
  142. Hill E. Belimumab Earns FDA Approval for Lupus. Medscape News. March 15, 2011. [Full Text].
  143. Brooks M. FDA Clears Self-injectable Belimumab (Benlysta) for SLE. Medscape Medical News. 2017 Jul 21. Available at https://www.medscape.com/viewarticle/883270.
  144. 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. 2011 Feb 26. 377(9767):721-31. [QxMD MEDLINE Link].
  145. 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 Dec. 63(12):3918-30. [QxMD MEDLINE Link].
  146. Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, et al. Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol. 2017 May. 69 (5):1016-1027. [QxMD MEDLINE Link]. [Full Text].
  147. Urowitz MB, Ohsfeldt RL, Wielage RC, Kelton KA, Asukai Y, Ramachandran S. Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis. Ann Rheum Dis. 2019 Mar. 78 (3):372-379. [QxMD MEDLINE Link].
  148. Lu TY, Ng KP, Cambridge G, Leandro MJ, Edwards JC, Ehrenstein M, et al. A retrospective seven-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients. Arthritis Rheum. 2009 Apr 15. 61(4):482-7. [QxMD MEDLINE Link].
  149. Hughes G. Rituximab in lupus and beyond: the state of the art. Lupus. 2009 Jun. 18(7):639-44. [QxMD MEDLINE Link].
  150. Murray E, Perry M. Off-label use of rituximab in systemic lupus erythematosus: a systematic review. Clin Rheumatol. 2010 Jul. 29(7):707-16. [QxMD MEDLINE Link].
  151. Terrier B, Amoura Z, Ravaud P, et al. Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French AutoImmunity and Rituximab registry. Arthritis Rheum. 2010 Aug. 62(8):2458-66. [QxMD MEDLINE Link].
  152. Aguiar R, Araújo C, Martins-Coelho G, Isenberg D. Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years. Arthritis Care Res (Hoboken). 2016 Apr 25. 10 (3):114-6. [QxMD MEDLINE Link].
  153. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010 Jan. 62(1):222-33. [QxMD MEDLINE Link].
  154. Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr. 64(4):1215-26. [QxMD MEDLINE Link].
  155. Furie RA, Morand EF, Bruce IN, Manzi S, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. The Lancet Rheumatology. 2019. 1(4):e208-e219.
  156. Morand EF, Furie R, Tanaka Y, Bruce IN, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16. 382 (3):211-221. [QxMD MEDLINE Link]. [Full Text].
  157. Furie R, Khamashta M, Merrill JT, Werth VP, et al. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb. 69 (2):376-386. [QxMD MEDLINE Link]. [Full Text].
  158. Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021 May 29. 397 (10289):2070-2080. [QxMD MEDLINE Link].
  159. Mougiakakos D, Krönke G, Völkl S, Kretschmann S, Aigner M, Kharboutli S, et al. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5. 385 (6):567-569. [QxMD MEDLINE Link].
  160. Mackensen A, Müller F, Mougiakakos D, Böltz S, Wilhelm A, Aigner M, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct. 28 (10):2124-2132. [QxMD MEDLINE Link].
  161. Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22. 390 (8):687-700. [QxMD MEDLINE Link].
  162. Andrade C, Mendonça T, Farinha F, Correia J, Marinho A, Almeida I, et al. Alveolar hemorrhage in systemic lupus erythematosus: a cohort review. Lupus. 2015 Sep 18. [QxMD MEDLINE Link].
  163. Pickering MC, Walport MJ. Links between complement abnormalities and systemic lupus erythematosus. Rheumatology (Oxford). 2000 Feb. 39(2):133-41. [QxMD MEDLINE Link].
  164. Ramos-Casals M, Campoamor MT, Chamorro A, et al. Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients. Lupus. 2004. 13(10):777-83. [QxMD MEDLINE Link].
  165. Mosca M, Tani C, Carli L, Bombardieri S. Glucocorticoids in systemic lupus erythematosus. Clin Exp Rheumatol. 2011 Sep-Oct. 29(5 Suppl 68):S126-9. [QxMD MEDLINE Link].
  166. Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O'Nan P, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004 Mar 4. 350(10):971-80. [QxMD MEDLINE Link].
  167. Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005 Nov 24. 353(21):2219-28. [QxMD MEDLINE Link].
  168. Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA. Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum. 2010 Jan. 62(1):211-21. [QxMD MEDLINE Link].
  169. Arora S, Rovin BH. Expert Perspective: An Approach to Refractory Lupus Nephritis. Arthritis Rheumatol. 2022 Jun. 74 (6):915-926. [QxMD MEDLINE Link].
  170. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct. 100 (4S):S1-S276. [QxMD MEDLINE Link]. [Full Text].
  171. Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17. 365(20):1886-95. [QxMD MEDLINE Link].
  172. Houssiau FA, D'Cruz D, Sangle S, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis. 2010 Dec. 69(12):2083-9. [QxMD MEDLINE Link]. [Full Text].
  173. Argolini LM, Frontini G, Elefante E, Saccon F, Binda V, Tani C, et al. Multicentric study comparing cyclosporine, mycophenolate mofetil and azathioprine in the maintenance therapy of lupus nephritis: 8 years follow up. J Nephrol. 2021 Apr. 34 (2):389-398. [QxMD MEDLINE Link].
  174. Bramham K, Hunt BJ, Bewley S, et al. Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J Rheumatol. 2011 Sep. 38(9):1906-13. [QxMD MEDLINE Link].
  175. [Guideline] Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020 Jun. 79 (6):713-723. [QxMD MEDLINE Link]. [Full Text].
  176. Long AA, Ginsberg JS, Brill-Edwards P, et al. The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb Haemost. 1991 Nov 1. 66(5):520-4. [QxMD MEDLINE Link].
  177. Richardson J. Pregnancy and Rheumatic Disease. American College of Rheumatology. Available at https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Living-Well-with-Rheumatic-Disease/Pregnancy-Rheumatic-Disease. June 2018; Accessed: August 4, 2021.
  178. Vinet E, Clarke AE, Gordon C, Urowitz MB, Hanly JG, Pineau CA, et al. Decreased live births in women with systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2011 Jul. 63(7):1068-72. [QxMD MEDLINE Link].
  179. Silverman E, Jaeggi E. Non-cardiac manifestations of neonatal lupus erythematosus. Scand J Immunol. 2010 Sep. 72(3):223-5. [QxMD MEDLINE Link].
  180. Hornberger LK, Al Rajaa N. Spectrum of cardiac involvement in neonatal lupus. Scand J Immunol. 2010 Sep. 72(3):189-97. [QxMD MEDLINE Link].
  181. Jaeggi E, Laskin C, Hamilton R, Kingdom J, Silverman E. The importance of the level of maternal anti-Ro/SSA antibodies as a prognostic marker of the development of cardiac neonatal lupus erythematosus a prospective study of 186 antibody-exposed fetuses and infants. J Am Coll Cardiol. 2010 Jun 15. 55(24):2778-84. [QxMD MEDLINE Link].
  182. Yazdany J, Panopalis P, Gillis JZ, Schmajuk G, MacLean CH, Wofsy D, et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum. 2009 Mar 15. 61(3):370-7. [QxMD MEDLINE Link]. [Full Text].
  183. Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005 Dec 15. 353(24):2550-8. [QxMD MEDLINE Link].
  184. Schmajuk G, Yelin E, Chakravarty E, Nelson LM, Panopolis P, Yazdany J. Osteoporosis screening, prevention, and treatment in systemic lupus erythematosus: application of the systemic lupus erythematosus quality indicators. Arthritis Care Res (Hoboken). 2010 Jul. 62(7):993-1001. [QxMD MEDLINE Link]. [Full Text].
  185. Schmajuk G, Schneeweiss S, Katz JN, et al. Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal. Arthritis Rheum. 2007 Aug 15. 57(6):928-34. [QxMD MEDLINE Link].
  186. Wajed J, Ahmad Y, Durrington PN, Bruce IN. Prevention of cardiovascular disease in systemic lupus erythematosus--proposed guidelines for risk factor management. Rheumatology (Oxford). 2004 Jan. 43(1):7-12. [QxMD MEDLINE Link].
  187. Scalzi LV, Hollenbeak CS, Wang L. Racial disparities in age at time of cardiovascular events and cardiovascular-related death in patients with systemic lupus erythematosus. Arthritis Rheum. 2010 Sep. 62(9):2767-75. [QxMD MEDLINE Link]. [Full Text].
  188. van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2011 Mar. 70(3):414-22. [QxMD MEDLINE Link].
  189. Yap KS, Northcott M, Hoi AB, Morand EF, Nikpour M. Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort. Lupus Sci Med. 2015. 2 (1):e000064. [QxMD MEDLINE Link].
  190. García-Carrasco M, Mendoza-Pinto C, Etchegaray-Morales I, Soto-Santillán P, Jiménez-Herrera EA, Robles-Sánchez V, et al. Vitamin D insufficiency and deficiency in mexican patients with systemic lupus erythematosus: Prevalence and relationship with disease activity. Reumatol Clin. 2016 Apr 12. [QxMD MEDLINE Link].
  191. Lin TC, Wu JY, Kuo ML, Ou LS, Yeh KW, Huang JL. Correlation between disease activity of pediatric-onset systemic lupus erythematosus and level of vitamin D in Taiwan: A case-cohort study. J Microbiol Immunol Infect. 2016 Jan 12. [QxMD MEDLINE Link].
  192. Schoindre Y, et al; Group PLUS. Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up. Lupus Sci Med. 2014. 1 (1):e000027. [QxMD MEDLINE Link]. [Full Text].
  193. Ibañez D, Gladman DD, Touma Z, Nikpour M, Urowitz MB. Optimal frequency of visits for patients with systemic lupus erythematosus to measure disease activity over time. J Rheumatol. 2011 Jan. 38(1):60-3. [QxMD MEDLINE Link].
  194. Feldman CH, Costenbader KH, Solomon DH, Subramanian SV, Kawachi I. Area-Level Predictors of Medication Nonadherence Among US Medicaid Beneficiaries With Lupus: A Multilevel Study. Arthritis Care Res (Hoboken). 2019 Jul. 71 (7):903-913. [QxMD MEDLINE Link].
  195. Koneru S, Shishov M, Ware A, Farhey Y, Mongey AB, Graham TB, et al. Effectively measuring adherence to medications for systemic lupus erythematosus in a clinical setting. Arthritis Rheum. 2007 Aug 15. 57 (6):1000-6. [QxMD MEDLINE Link].
  196. Petri M. Drug monitoring in systemic lupus erythematosus. Curr Opin Pharmacol. 2022 Jun. 64:102225. [QxMD MEDLINE Link].
  197. Garg S, Unnithan R, Hansen KE, Costedoat-Chalumeau N, Bartels CM. Clinical Significance of Monitoring Hydroxychloroquine Levels in Patients With Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken). 2021 May. 73 (5):707-716. [QxMD MEDLINE Link].
  198. Bhana S. Azathioprine (Imuran). American College of Rheumatology. Available at https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Azathioprine-Imuran. December 2020; Accessed: August 4, 2021.
  199. Boumpas DT, Austin HA 3rd, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 1992 Sep 26. 340(8822):741-5. [QxMD MEDLINE Link].
  200. Houssiau FA, Vasconcelos C, D'Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis. 2010 Jan. 69(1):61-4. [QxMD MEDLINE Link].
  201. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005 Nov 24. 353(21):2219-28. [QxMD MEDLINE Link].
  202. Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009 May. 20(5):1103-12. [QxMD MEDLINE Link]. [Full Text].
  203. Isenberg D, Appel GB, Contreras G, et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford). 2010 Jan. 49(1):128-40. [QxMD MEDLINE Link]. [Full Text].

Author

Coauthor(s)

Shivani Garg, MD, MS Assistant Professor (CHS), Division of Rheumatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health; Director, Lupus Clinic, Co-Director, Lupus Nephritis Clinic, UW Health

Shivani Garg, MD, MS is a member of the following medical societies: American College of Rheumatology, American Medical Association, American Society of Nephrology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Acknowledgements

Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Julie Hildebrand, MD Consulting Staff, Department of Internal Medicine, Associated Physicians of Madison, WI

Disclosure: Nothing to disclose.

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Viraj S Lakdawala, MD Clinical Instructor of Emergency Medicine, University of California, San Francisco, School of Medicine; Attending Physician, San Francisco General Hospital

Viraj S Lakdawala, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Mark J Leber, MD, MPH Assistant Professor of Emergency Medicine in Clinical Medicine, Weill Cornell Medical College; Attending Physician, Lincoln Medical and Mental Health Center

Mark J Leber, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and American College of Physicians

Disclosure: Nothing to disclose.

Carlos J Lozada, MD Director of Rheumatology Fellowship Program, Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Pfizer Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Anuritha Tirumani, MD Research Coordinator, Department of Emergency Medicine, Brooklyn Hospital Center

Disclosure: Nothing to disclose.

Acknowledgements

The authors would like to thank Joanna Wong for assistance in preparation of revisions to this topic.