Systemic Lupus Erythematosus (SLE) 

  • Author: Christie M Bartels, MD, MS; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 18, 2012
 

Background

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. It is characterized by an autoantibody response to nuclear and cytoplasmic antigens. SLE can affect any organ system, but mainly involves the skin, joints, kidneys, blood cells, and nervous system (see Clinica l).

The diagnosis of SLE must be based on the proper constellation of clinical findings and laboratory evidence. American College of Rheumatology (ACR) criteria summarize features necessary for diagnosis. (See Workup.) Management depends on disease severity and organ involvement. Periodic follow-up and laboratory testing are imperative to detect signs and symptoms of new organ-system involvement and to monitor the response or adverse reactions to therapies. (See Treatment.)

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Pathophysiology

SLE is an autoimmune disorder characterized by multisystem microvascular inflammation with the generation of autoantibodies. Although the specific cause of SLE is unknown, multiple factors are associated with the development of the disease, including genetic, racial, hormonal, and environmental factors.[1, 2, 3] Many immune disturbances, both innate and acquired, occur in SLE (see the image below).

In systemic lupus erythematosus (SLE), many genetiIn systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity.

One longstanding proposed mechanism for the development of autoantibodies involves a defect in apoptosis that causes increased cell death and a disturbance in immune tolerance.[4, 5, 2, 6] The redistribution of cellular antigens during necrosis/apoptosis leads to a cell-surface display of plasma and nuclear antigens in the form of nucleosomes. Subsequently, dysregulated (intolerant) lymphocytes begin targeting normally protected intracellular antigens. Recent genetic studies point to disruptions in lymphocyte signalling, interferon response, clearance of complement and immune complexes, apoptosis, and DNA methylation.[7]

Many clinical manifestations of SLE are mediated via circulating immune complexes in various tissues or the direct effects of antibodies to cell surface components. Immune complexes form in the microvasculature, leading to complement activation and inflammation. Moreover, antibody-antigen complexes deposit on the basement membranes of skin and kidneys. In active SLE, this process has been confirmed by demonstration of complexes of nuclear antigens such as DNA, immunoglobulins, and complement proteins at these sites.

Serum antinuclear antibodies (ANAs) are found in nearly all individuals with active SLE. Antibodies to native double-stranded DNA (dsDNA) are relatively specific for the diagnosis of SLE. Whether polyclonal B-cell activation or a response to specific antigens exists is unclear, but much of the pathology involves B cells, T cells, and dendritic cells. Cytotoxic T cells and suppressor T cells (which would normally down-regulate immune responses) are decreased. The generation of polyclonal T-cell cytolytic activity is impaired. Helper (CD4+) T cells are increased. A lack of immune tolerance is observed in animal lupus models. Recent reports pointing to important roles of interferon alpha, transcription factors, and signaling variations also point to a central role for neutrophils.[8]

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Etiology

Although the specific cause of SLE is unknown, multiple genetic predispositions and gene-environment interactions have been identified (see chart below). This complex situation perhaps explains the variable clinical manifestations in persons with SLE.

In systemic lupus erythematosus (SLE), many genetiIn systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity.

Some studies have synthesized what is known about the mechanisms of SLE disease and genetic associations.[2, 7, 9] At least 35 genes are known to increase the risk of SLE.[7] A genetic predisposition is supported by the 40% concordance among monozygotic twins. If a mother has SLE, her daughter's risk of developing the disease has been estimated at 1:40 and her son's risk is 1:250.

Studies of human leukocyte antigens (HLA) reveal that HLA-A1, B8, and DR3 are more common in persons with SLE than in the general population. The presence of the null complement alleles and congenital deficiencies of complement (especially C4, C2, and other early components) are also associated with an increased risk of SLE.

Numerous studies have investigated the role of infectious etiologies that may also perpetuate autoimmunity.[10] Patients with SLE have higher titers of antibodies to Epstein-Barr virus (EBV), have increased circulating EBV viral loads, and make antibodies to retroviruses, including to protein regions homologous to nuclear antigens. Viruses may stimulate specific cells in the immune network. Chronic infections may induce anti-DNA antibodies or even lupuslike symptoms, and acute lupus flares often follow bacterial infections.

Environmental and exposure-related causes of SLE are less clear. Silica dust and cigarette smoking may increase the risk of developing SLE. Administration of estrogen to postmenopausal women appears to increase the risk of developing SLE. Breastfeeding is associated with a decreased risk of developing SLE. Photosensitivity is clearly a precipitant of skin disease.

The results of one study suggest that low vitamin D levels increase autoantibody production in healthy individuals; vitamin D deficiency was also linked to B-cell hyperactivity and interferon-alpha activity in patients with SLE.[11]

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Epidemiology

United States statistics

In the United States, the annual incidence of SLE averages 5.1 per 100,000 population. The reported prevalence is 52 cases per 100,000 population.[12] According to a 2008 report from the National Arthritis Data Working Group, approximately 250,000 Americans have SLE.[13] The frequency of SLE could be increasing due to milder forms of the disease that are now being recognized.

The frequency of SLE varies by race and ethnicity, with higher rates reported among black and Hispanic people. The prevalence of SLE is approximately 40 per 100,000 whites in Rochester, Minnesota, versus 100 per 100,000 Hispanic persons in Nogales, Arizona.[14, 15] The incidence of SLE in black women is approximately 4 times higher than in white women. SLE is also more frequent in Asian women than in white women.[14]

International statistics

Worldwide, the prevalence of SLE varies. The highest prevalences have been reported in Italy, Spain, Martinique, and the United Kingdom Afro-Caribbean population.[12] Although the prevalence of SLE is high in black persons in the United Kingdom, the disease is rarely reported among blacks who live in Africa, suggesting that there may be an environmental trigger as well as a genetic basis for their disease.[16]

Race-, sex-, and age-related demographics

Worldwide, the prevalence of SLE appears to vary by race. However, different prevalence rates occur among people of the same race in different geographical locations. The contrast between low reported rates of SLE in Africa and high rates among black women in the United Kingdom suggests the importance of environmental influences.[16] In general, black women have a higher rate of SLE than any other race, followed by Asians, then white women.[12] In the United States, black women are 4 times more likely to have SLE than white women.[12]

SLE frequently starts in women of childbearing age, and the use of exogenous hormones has been associated with lupus onset and flares, suggesting a role for hormonal factors in the pathogenesis of the disease.[17] The risk of SLE development in men is similar to that in prepubertal or postmenopausal women. Interestingly, SLE is more common in men with Klinefelter syndrome (ie, genotype XXY) than in men without the syndrome, also supporting a hormonal hypothesis.

The female-to-male ratio peaks at 11:1 during the childbearing years.[18] A correlation between age and incidence of SLE mirrors peak years of female sex hormone production. Onset of SLE is usually after puberty, typically in the 20s and 30s, with 20% of all cases diagnosed during the first 2 decades of life.[19] The prevalence of SLE is highest among women aged 14-64 years. SLE does not have an age predilection in males, although it should be noted that among older adults, the female-to-male ratio falls.[20]

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Prognosis

SLE carries a highly variable prognosis for individual patients. The natural history of SLE ranges from relatively benign disease to rapidly progressive and even fatal disease. SLE often waxes and wanes in affected individuals throughout life, and features of the disease vary greatly between individuals. The disease course is milder and survival rate higher among persons with isolated skin and musculoskeletal involvement than in those with renal[21] and CNS disease.[22] A recent consortium report of 298 SLE patients followed for 5.5 years noted falls in SLE Disease Activity Index 2000 (SLEDAI-2K) scores after the first year of clinical follow up and gradual increases in cumulative mean Systemic Lupus International Collaborating Clinics (SLICC) damage index scores.[23]

Mortality in patients with SLE has decreased over the past 20 years.[24] Prior to 1955, the 5-year survival rate in SLE was less than 50%; currently, the average 10-year survival rate exceeds 90%,[25, 22] and the 15-year survival rate is approximately 80%.[26] Ten-year survival rates in other countries within Asia and Africa are significantly lower, ranging from 60-70%,[27, 28] but may reflect detection bias of severe cases only.

Decreased mortality rates associated with SLE can be attributed to earlier diagnosis (including milder cases), improvement in disease-specific treatments, and advances in general medical care. Yet, according to the Centers for Disease Control and Prevention, however, one third of SLE-related deaths in the United States occur in patients younger than 45 years, making this a serious issue despite declining overall mortality rates.[29]

In 1976, Urowitz first reported bimodal mortality in early versus late SLE, noting that SLE-related deaths usually occur within the first 5-10 years of symptom onset.[30] Mortality in the first few years of illness is typically from severe SLE disease (eg, CNS, renal, or cardiovascular involvement) or infection related to immunosuppressive treatment. Infections account for 29% of all deaths in these patients.[31]

Late deaths (after age 35 years) are generally from myocardial infarction or stroke secondary to accelerated atherosclerosis.[24, 32, 25, 33] Manzi et al reported that women aged 35-44 years with SLE were 50 times more likely to develop myocardial ischemia than healthy Framingham control women.[32] The presence of lupus nephritis may increase these risks.[34]

Causes of accelerated coronary artery disease in persons with SLE are likely multifactorial. They include endothelial dysfunction, inflammatory mediators, corticosteroid-induced atherogenesis, and dyslipidemia.

The influence of race on prognosis has been widely debated. The LUMINA study group examined SLE among black, white, and Hispanic patients in the United States (including Puerto Rico) and reported that both disease activity and poverty predicted higher mortality among racial and ethnic minorities.[35]

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Patient Education

Stress the importance of adherence with medications and follow-up appointments for detection and control of SLE disease. Instruct patients with SLE to seek medical care for evaluation of new symptoms, including fever. Advise them regarding their hightened risks for infection and cardiovascular disease. Educate patients with SLE regarding aggressive lipid and blood pressure goals to minimize the risk of coronary artery disease.

Instruct patients with SLE to avoid exposure to sunlight and ultraviolet light. Encourage them to receive nonlive vaccines during stable periods of disease, to quit smoking, and to carefully plan pregnancies.

For patient education information, see the Arthritis Center, as well as Lupus (Systemic Lupus Erythematosus.

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Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Christie M Bartels, MD, MS  Assistant Professor of Rheumatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health

Christie M Bartels, MD, MS is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Daniel Muller, MD, PhD  Associate Professor of Rheumatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health

Daniel Muller, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, and American Holistic Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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

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.

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.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Julie Hildebrand, MD, and Anuritha Tirumani, MD, to the development and writing of the source articles.

References

  1. 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. Oct 1998;41(10):1714-24. [Medline].

  2. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. Feb 28 2008;358(9):929-39. [Medline].

  3. D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. Feb 17 2007;369(9561):587-96. [Medline].

  4. Andrade F, Casciola-Rosen L, Rosen A. Apoptosis in systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am. May 2000;26(2):215-27, v. [Medline].

  5. Hahn BH, Karpouza GA, Tsao BP. Pathogenesis of systemic lupus erythematosus. In: Harris ED, et al, eds. Kelley's Textbook of Rheumatology. 7th ed. Philadelphia, Pa: WB Saunders; 2005:1174-1200.

  6. Munoz LE, Gaipl US, Franz S, Sheriff A, Voll RE, Kalden JR, et al. SLE--a disease of clearance deficiency?. Rheumatology (Oxford). Sep 2005;44(9):1101-7. [Medline].

  7. Sestak AL, Fürnrohr BG, Harley JB, Merrill JT, Namjou B. The genetics of systemic lupus erythematosus and implications for targeted therapy. Ann Rheum Dis. Mar 2011;70 Suppl 1:i37-43. [Medline].

  8. Bosch X. Systemic lupus erythematosus and the neutrophil. N Engl J Med. Aug 25 2011;365(8):758-60. [Medline].

  9. Sanchez E, Nadig A, Richardson BC, et al. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis. Oct 2011;70(10):1752-7. [Medline].

  10. 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. Nov 2009;18(13):1136-43. [Medline].

  11. Ritterhouse LL, Crowe SR, Niewold TB, et al. Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus. Ann Rheum Dis. Sep 2011;70(9):1569-74. [Medline]. [Full Text].

  12. Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus. 2006;15(5):308-18. [Medline].

  13. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. Jan 2008;58(1):15-25. [Medline].

  14. Uramoto KM, Michet CJ Jr, Thumboo J, Sunku J, O'Fallon WM, Gabriel SE. Trends in the incidence and mortality of systemic lupus erythematosus, 1950-1992. Arthritis Rheum. Jan 1999;42(1):46-50. [Medline].

  15. Balluz L, Philen R, Ortega L, Rosales C, Brock J, Barr D, et al. Investigation of systemic lupus erythematosus in Nogales, Arizona. Am J Epidemiol. Dec 1 2001;154(11):1029-36. [Medline].

  16. Symmons DP. Frequency of lupus in people of African origin. Lupus. Jun 1995;4(3):176-8. [Medline].

  17. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. Apr 2007;56(4):1251-62. [Medline].

  18. Manzi S. Epidemiology of systemic lupus erythematosus. Am J Manag Care. Oct 2001;7(16 Suppl):S474-9. [Medline].

  19. Klein-Gitelman M, Reiff A, Silverman ED. Systemic lupus erythematosus in childhood. Rheum Dis Clin North Am. Aug 2002;28(3):561-77, vi-vii. [Medline].

  20. 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). Nov 2004;83(6):348-59. [Medline].

  21. 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). Jun 2010;62(6):873-80. [Medline].

  22. Kasitanon N, Magder LS, Petri M. Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore). May 2006;85(3):147-56. [Medline].

  23. 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). Jan 2012;64(1):132-7. [Medline].

  24. Ruiz-Irastorza G, Khamashta MA, Castellino G, Hughes GR. Systemic lupus erythematosus. Lancet. Mar 31 2001;357(9261):1027-32. [Medline].

  25. Trager J, Ward MM. Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol. Sep 2001;13(5):345-51. [Medline].

  26. 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. Jul 1995;22(7):1265-70. [Medline].

  27. 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. Jul-Aug 1997;10(4):159-64. [Medline].

  28. 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. [Medline].

  29. Office of Minority Health & Health Disparities (OMHD). Eliminate Disparities in Lupus. Available at http://www.cdc.gov/omhd/amh/factsheets/lupus.htm. Accessed May 14, 2008.

  30. Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med. Feb 1976;60(2):221-5. [Medline].

  31. 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). May 1999;78(3):167-75. [Medline].

  32. 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. Mar 1 1997;145(5):408-15. [Medline].

  33. 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.

  34. Faurschou M, Mellemkjaer L, Starklint H, et al. High risk of ischemic heart disease in patients with lupus nephritis. J Rheumatol. Nov 2011;38(11):2400-5. [Medline].

  35. 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. Apr 2001;45(2):191-202. [Medline].

  36. DUBOIS EL, TUFFANELLI DL. CLINICAL MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS. COMPUTER ANALYSIS OF 520 CASES. JAMA. Oct 12 1964;190:104-11. [Medline].

  37. HARVEY AM, SHULMAN LE, TUMULTY PA, CONLEY CL, SCHOENRICH EH. Systemic lupus erythematosus: review of the literature and clinical analysis of 138 cases. Medicine (Baltimore). Dec 1954;33(4):291-437. [Medline].

  38. Edworthy SM. Clinical Manifestations of Systemic Lupus Erythematosus. In: Harris ED, et al, eds. Kelley's Textbook of Rheumatology. 7th ed. Philadelphia, Pa: WB Saunders; 2005:1201-24.

  39. Wallace D, Edmund D, eds. Dubois' Lupus Erythematosus. Philadelphia, Pa: Lippincott Williams & Wilkins.; 2006.

  40. Jennekens FG, Kater L. The central nervous system in systemic lupus erythematosus. Part 1. Clinical syndromes: a literature investigation. Rheumatology (Oxford). Jun 2002;41(6):605-18. [Medline].

  41. Jennekens FG, Kater L. The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic mechanisms of clinical syndromes: a literature investigation. Rheumatology (Oxford). Jun 2002;41(6):619-30. [Medline].

  42. 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. Dec 2010;69(12):2074-82. [Medline].

  43. Varaprasad IR, Agrawal S, Prabu VN, Rajasekhar L, Kanikannan MA, Narsimulu G. Posterior reversible encephalopathy syndrome in systemic lupus erythematosus. J Rheumatol. Aug 2011;38(8):1607-11. [Medline].

  44. 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. Oct 2010;37(10):2032-8. [Medline].

  45. 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. Mar 16 2009;9:11. [Medline]. [Full Text].

  46. 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). Nov 2008;87(6):311-8. [Medline].

  47. Fessler BJ. Infectious diseases in systemic lupus erythematosus: risk factors, management and prophylaxis. Best Pract Res Clin Rheumatol. Apr 2002;16(2):281-91. [Medline].

  48. Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus in children and adults. Neurol Clin. Feb 2010;28(1):61-73. [Medline]. [Full Text].

  49. Lin YC, Wang AG, Yen MY. Systemic lupus erythematosus-associated optic neuritis: clinical experience and literature review. Acta Ophthalmol. Mar 2009;87(2):204-10. [Medline].

  50. Williams EL, Gadola S, Edwards CJ. Anti-TNF-induced lupus. Rheumatology (Oxford). Jul 2009;48(7):716-20. [Medline].

  51. Tierney, et al. Current Medical Diagnosis and Treatment. 2001:841-844.

  52. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. Nov 1982;25(11):1271-7. [Medline].

  53. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. Sep 1997;40(9):1725. [Medline].

  54. Elkon KB. Systemic lupus erythematosus: autoantibodies in SLE. In: Klippel JH, Dieppe PA, eds. Rheumatology. 2nd ed. St. Louis, Mo: Mosby; 1998.

  55. Hanly JG, Urowitz MB, Su L, et al. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis. Oct 2011;70(10):1726-32. [Medline].

  56. Czeizel A. A case-control analysis of the teratogenic effects of co-trimoxazole. Reprod Toxicol. 1990;4(4):305-13. [Medline].

  57. 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:[Medline].

  58. 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. Jan 2011;38(1):60-3. [Medline].

  59. Yazdany J, Panopalis P, Gillis JZ, Schmajuk G, MacLean CH, Wofsy D, et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum. Mar 15 2009;61(3):370-7. [Medline]. [Full Text].

  60. Hahn BH. Management of Systemic Lupus Erythematosus. In: Harris ED, et al, eds. Kelley's Textbook of Rheumatology. 7th ed. Philadelphia, Pa: WB Saunders; 2005:1225-47.

  61. 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. Nov 2011;38(11):2382-9. [Medline].

  62. 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. Feb 26 2011;377(9767):721-31. [Medline].

  63. Hill E. Belimumab Earns FDA Approval for Lupus. Medscape News [serial online]. March 15, 2011;Accessed August 11, 2011. Available at http://www.medscape.com/viewarticle/738729.

  64. 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. Apr 15 2009;61(4):482-7. [Medline].

  65. 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. Jan 2010;62(1):222-33. [Medline].

  66. 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. Sep 2007;66(9):1168-72. [Medline]. [Full Text].

  67. Yazdany J, Panopalis P, Gillis JZ, Schmajuk G, MacLean CH, Wofsy D, et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum. Mar 15 2009;61(3):370-7. [Medline]. [Full Text].

  68. 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. Dec 15 2005;353(24):2550-8. [Medline].

  69. 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). Jul 2010;62(7):993-1001. [Medline]. [Full Text].

  70. Schmajuk G, Schneeweiss S, Katz JN, et al. Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal. Arthritis Rheum. Aug 15 2007;57(6):928-34. [Medline].

  71. Wajed J, Ahmad Y, Durrington PN, Bruce IN. Prevention of cardiovascular disease in systemic lupus erythematosus--proposed guidelines for risk factor management. Rheumatology (Oxford). Jan 2004;43(1):7-12. [Medline].

  72. 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. Sep 2010;62(9):2767-75. [Medline]. [Full Text].

  73. 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. Mar 2011;70(3):414-22. [Medline].

  74. Elkayam O, Amir S, Mendelson E, Schwaber M, Grotto I, Wollman J, et al. Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among patients with rheumatic diseases. Arthritis Care Res (Hoboken). Jul 2011;63(7):1062-7. [Medline].

  75. Bramham K, Hunt BJ, Bewley S, et al. Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J Rheumatol. Sep 2011;38(9):1906-13. [Medline].

  76. 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). Jul 2011;63(7):1068-72. [Medline].

  77. Silverman E, Jaeggi E. Non-cardiac manifestations of neonatal lupus erythematosus. Scand J Immunol. Sep 2010;72(3):223-5. [Medline].

  78. Hornberger LK, Al Rajaa N. Spectrum of cardiac involvement in neonatal lupus. Scand J Immunol. Sep 2010;72(3):189-97. [Medline].

  79. 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. Sep 26 1992;340(8822):741-5. [Medline].

  80. 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. Jan 2010;69(1):61-4. [Medline].

  81. 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. Nov 24 2005;353(21):2219-28. [Medline].

  82. Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. May 2009;20(5):1103-12. [Medline]. [Full Text].

  83. Isenberg D, Appel GB, Contreras G, et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford). Jan 2010;49(1):128-40. [Medline]. [Full Text].

  84. 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. Dec 2010;69(12):2083-9. [Medline]. [Full Text].

  85. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken). Jun 2010;62(6):775-84. [Medline].

  86. Griffiths B, Emery P, Ryan V, Isenberg D, Akil M, Thompson R, et al. The BILAG multi-centre open randomized controlled trial comparing ciclosporin vs azathioprine in patients with severe SLE. Rheumatology (Oxford). Apr 2010;49(4):723-32. [Medline].

 
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In systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity.
The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.
Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.
This axial, T2-weighted brain MRI demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with long-standing systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. Distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to distribution.
Table 1. Drugs Associated With Lupus Erythematosus
Definite Association
ChlorpromazineMethyldopa
HydralazineProcainamide
IsoniazidQuinidine
Possible Association
Beta-blockersMethimazole
CaptoprilNitrofurantoin
CarbamazepinePenicillamine
CimetidinePhenytoin
EthosuximidePropylthiouracil
HydrazinesSulfasalazine
LevodopaSulfonamides
LithiumTrimethadione
Unlikely Association
AllopurinolPenicillin
ChlorthalidonePhenylbutazone
Gold



salts



Reserpine
GriseofulvinStreptomycin
MethysergideTetracyclines
Oral contraceptives
*Data from Tierney et al.[51]
Table 1. American College of Rheumatology Diagnostic Criteria
CriterionDefinition
1. Malar rashFixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds
2. Discoid rashErythematous raised patches with adherent keratotic scaling and follicular plugging (Atrophic scarring may occur in older lesions)
3. PhotosensitivitySkin rash as a result of unusual reaction to sunlight, by patient history or physician observation
4. Oral ulcersOral or nasopharyngeal ulceration, usually painless, observed by a physician
5. ArthritisNonerosive arthritis involving ≥2 peripheral joints, characterized by tenderness, swelling, or effusion
6. Serositis(A) Pleuritis: Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion



or



(B) Pericarditis: Documented by ECG or rub or evidence of pericardial effusion
7. Renal disorder(A) Persistent proteinuria >0.5 g/d or >3+ if quantitation not performed



or



(B) Cellular casts: May be red blood cell, hemoglobin, granular, tubular, or mixed
8. Neurologic disorder(A) Seizures: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)



or



(B) Psychosis: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)
9. Hematologic disorder(A) Hemolytic anemia: With reticulocytosis



or



(B) Leukopenia: < 4000/mm3 total on ≥2 occasions



or



(C) Lymphopenia: < 1500/mm3 on ≥2 occasions



or



(D) Thrombocytopenia: < 100,000/mm3 in the absence of offending drugs
10. Immunologic disorder(A) Anti-DNA: Antibody to native DNA in abnormal titer



or



(B) Anti-Sm: Presence of antibody to Sm nuclear antigen



or



(C) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption tests
11. Antinuclear antibodyAn abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome
SLE can be diagnosed if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation.
Table 2. International Society of Nephrology 2003 Revised Classification of SLE Nephritis[57]
ClassClassificationFeatures
Class IMinimal mesangialNormal light microscopy findings; abnormal electron microscopy findings
Class IIMesangial proliferativeHypercellular on light microscopy
Class IIIFocal proliferative< 50% of glomeruli involved
Class IVDiffuse proliferative>50% of glomeruli involved; classified segmental or global; treated aggressively
Class VMembranousPredominantly nephrotic disease
Class VIAdvanced sclerosingChronic lesions and sclerosis
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