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{{Short description|Human autoimmune disease}}{{cs1 config|name-list-style=vanc|display-authors=6}}{{redirect|SLE}}{{about|the most common type of lupus|the broader group of diseases|Lupus erythematosus|other uses}}{{Pp-semi-indef}}{{Update|part=Bit about new drug possibilities|date=December 2023}}{{More citations needed|date=March 2024}}

factoids

{{respellEM_pəsERReeTOH|səs}}arthritis>Painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, Lymphadenopathy, fatigue>feeling tired, red rash| complications = | onset = 15–45 years of age| duration = Long term| causes = Unclear| risks = | diagnosis = Based on symptoms and blood tests| differential = | prevention = | treatment = NSAIDs, corticosteroids, immunosuppressive drug>immunosuppressants, hydroxychloroquine, methotrexatePUBLISHER=LIPPINCOTT WILLIAMS & WILKINSPAGE=969URL=HTTPS://BOOKS.GOOGLE.COM/BOOKS?ID=4LEX_5VWY-4C&PG=PA969, 13 June 2016, | frequency = 2–7 per 10,000| deaths = }}Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body.WEB, Handout on Health: Systemic Lupus Erythematosus,weblink www.niams.nih.gov, 12 June 2016, February 2015, live,weblink" title="web.archive.org/web/20160617162703weblink">weblink 17 June 2016, Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.The cause of SLE is not clear. It is thought to involve a combination of genetics and environmental factors. Among identical twins, if one is affected there is a 24% chance the other one will also develop the disease. Female sex hormones, sunlight, smoking, vitamin D deficiency, and certain infections are also believed to increase a person's risk. The mechanism involves an immune response by autoantibodies against a person's own tissues. These are most commonly anti-nuclear antibodies and they result in inflammation. Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests. There are a number of other kinds of lupus erythematosus including discoid lupus erythematosus, neonatal lupus, and subacute cutaneous lupus erythematosus.There is no cure for SLE, but there are experimental and symptomatic treatments.WEB, 2022-09-15, Five lupus patients enter long-lasting remission after immunotherapy,weblink 2022-09-17, New Atlas, en-US, Treatments may include NSAIDs, corticosteroids, immunosuppressants, hydroxychloroquine, and methotrexate. Although corticosteroids are rapidly effective, long-term use results in side effects.JOURNAL, Davis LS, Reimold AM, Research and therapeutics-traditional and emerging therapies in systemic lupus erythematosus, Rheumatology, 56, suppl_1, i100–i113, April 2017, 28375452, 5850311, 10.1093/rheumatology/kew417, Alternative medicine has not been shown to affect the disease. Men have higher mortality.JOURNAL, Murphy G, Isenberg D, Effect of gender on clinical presentation in systemic lupus erythematosus, Rheumatology, 52, 12, 2108–2115, December 2013, 23641038, 10.1093/rheumatology/ket160, free, SLE significantly increases the risk of cardiovascular disease, with this being the most common cause of death. While women with lupus have higher risk pregnancies, most are successful.Rate of SLE varies between countries from 20 to 70 per 100,000. Women of childbearing age are affected about nine times more often than men.JOURNAL, Lisnevskaia L, Murphy G, Isenberg D, Systemic lupus erythematosus, The Lancet, 384, 9957, 1878–1888, November 2014, 24881804, 10.1016/s0140-6736(14)60128-8, 28905456, 10.1.1.1008.5428, While it most commonly begins between the ages of 15 and 45, a wide range of ages can be affected.JOURNAL, Danchenko N, Satia JA, Anthony MS, Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden, Lupus, 15, 5, 308–318, 2006, 16761508, 10.1191/0961203306lu2305xx, 6465663, Those of African, Caribbean, and Chinese descent are at higher risk than those of European descent. Rates of disease in the developing world are unclear.JOURNAL, Tiffin N, Adeyemo A, Okpechi I, A diverse array of genetic factors contribute to the pathogenesis of systemic lupus erythematosus, Orphanet Journal of Rare Diseases, 8, 2, January 2013, 23289717, 3551738, 10.1186/1750-1172-8-2, free, Lupus is Latin for "wolf": the disease was so-named in the 13th century as the rash was thought to appear like a wolf's bite.BOOK, Chabner DE, The Language of Medicine, 2013, Elsevier Health Sciences, 978-1-4557-2846-6, 610,weblink {{TOC limit}}

Signs and symptoms

(File:Symptoms of SLE.png|thumb|Common symptoms of SLEWEB, Shiel Jr WC, Stöppler MC,weblink MedicineNet, Systemic Lupus (cont.),weblink" title="web.archive.org/web/20091220005309weblink">weblink 2009-12-20, 2009-01-30, )SLE is one of several diseases known as "the great imitator" because it often mimics or is mistaken for other illnesses.WEB,weblink Lupus, "The Great Imitator", University Health Care, 2009-02-03,weblink" title="web.archive.org/web/20090115100021weblink">weblink January 15, 2009, SLE is a classical item in differential diagnosis, because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people having unexplained symptoms of SLE for years before a definitive diagnosis is reached.WEB, Lupus facts and statistics {{!, Lupus Foundation of America |url=https://www.lupus.org/resources/lupus-facts-and-statistics |access-date=2023-11-02 |website=www.lupus.org |language=en}}Common initial and chronic complaints include fever, malaise, joint pains, muscle pains, and fatigue. Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive.WEB, Lupus: Symptoms â€” MayoClinic.com,weblink 2008-07-14, live,weblink" title="web.archive.org/web/20080714123532weblink">weblink 2008-07-14, While SLE can occur in both males and females, it is found far more often in women, and the symptoms associated with each sex are different. Females tend to have a greater number of relapses, a low white blood cell count, more arthritis, Raynaud syndrome, and psychiatric symptoms. Males tend to have more seizures, kidney disease, serositis (inflammation of tissues lining the lungs and heart), skin problems, and peripheral neuropathy.JOURNAL, Yacoub Wasef SZ, Gender differences in systemic lupus erythematosus, Gender Medicine, 1, 1, 12–17, August 2004, 16115579, 10.1016/S1550-8579(04)80006-8,

Skin

(File:Fox Plate XLV.jpg|thumb|Lupus patches on the cheek, ear, and scalp)File:Sequeira Plate 38.jpg|thumb|Widespread lupus patches across the face with an epitheliomaepitheliomaAs many as 70% of people with lupus have some skin symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (commonly known as the butterfly rash) associated with the disease.JOURNAL, Tebbe B, Orfanos CE, Epidemiology and socioeconomic impact of skin disease in lupus erythematosus, Lupus, 6, 2, 96–104, 1997, 9061657, 10.1177/096120339700600204, 25969434, This rash occurs in 30–60% of people with SLE.BOOK, Harris JP, Weisman MH, Head and neck manifestations of systemic disease, 2007, Informa Healthcare, New York, 978-1-4200-1756-4, 6,weblink Hair loss, mouth and nasal ulcers, and lesions on the skin are other possible manifestations.WEB, Gladman D, Overview of the clinical manifestations of systemic lupus erythematosus in adults,weblink UpToDate, 18 April 2017, 10 September 2015, subscription, live,weblink 19 April 2017,

Muscles and bones

The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. More than 90 percent of those affected will experience joint or muscle pain at some time during the course of their illness.Joint and Muscle Pain {{webarchive|url=https://web.archive.org/web/20071109161325weblink |date=2007-11-09 }} Lupus Foundation of America Unlike rheumatoid arthritis, lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of the hands and feet. People with SLE are at particular risk of developing osteoarticular tuberculosis.JOURNAL, Hodkinson B, Musenge E, Tikly M, Osteoarticular tuberculosis in patients with systemic lupus erythematosus, QJM, 102, 5, 321–328, May 2009, 19246552, 10.1093/qjmed/hcp015, free, A possible association between rheumatoid arthritis and SLE has been suggested,JOURNAL, Hemminki K, Li X, Sundquist J, Sundquist K, Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions, Arthritis and Rheumatism, 60, 3, 661–668, March 2009, 19248111, 10.1002/art.24328, free, and SLE may be associated with an increased risk of bone fractures in relatively young women.JOURNAL, Mendoza-Pinto C, García-Carrasco M, Sandoval-Cruz H, Muñoz-Guarneros M, Escárcega RO, Jiménez-Hernández M, Munguía-Realpozo P, Sandoval-Cruz M, Delezé-Hinojosa M, López-Colombo A, Cervera R, Risk factors of vertebral fractures in women with systemic lupus erythematosus, Clinical Rheumatology, 28, 5, 579–585, May 2009, 19224131, 10.1007/s10067-009-1105-3, 29786198,

Blood

Anemia is common in children with SLEJOURNAL, Lam SK, Quah TC, Anemia in systemic lupus erythematosus, The Journal of the Singapore Paediatric Society, 32, 3–4, 132–136, 1990, 2133750, and develops in about 50% of cases.JOURNAL, Giannouli S, Voulgarelis M, Ziakas PD, Tzioufas AG, Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment, Annals of the Rheumatic Diseases, 65, 2, 144–148, February 2006, 16079164, 1798007, 10.1136/ard.2005.041673, Low platelet count (thrombocytopenia) and low white blood cell count (leukopenia) may be due to the disease or a side effect of pharmacological treatment. People with SLE may have an association with antiphospholipid antibody syndromeJOURNAL, Syuto T, Shimizu A, Takeuchi Y, Tanaka S, Hasegawa M, Nagai Y, Tamura A, Ishikawa O, Association of antiphosphatidylserine/prothrombin antibodies with neuropsychiatric systemic lupus erythematosus, Clinical Rheumatology, 28, 7, 841–845, July 2009, 19224124, 10.1007/s10067-009-1123-1, 26215523, (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged partial thromboplastin time (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term "lupus anticoagulant-positive". Another autoantibody finding in SLE is the anti-cardiolipin antibody, which can cause a false positive test for syphilis.{{citation needed|date=September 2011}}

Heart

SLE may cause pericarditis (inflammation of the outer lining surrounding the heart), myocarditis (inflammation of the heart muscle), or endocarditis (inflammation of the inner lining of the heart). The endocarditis of SLE is non-infectious, and is also called Libman–Sacks endocarditis. It involves either the mitral valve or the tricuspid valve. Atherosclerosis also occurs more often and advances more rapidly than in the general population.JOURNAL, Hahn BH, Systemic lupus erythematosus and accelerated atherosclerosis, The New England Journal of Medicine, 349, 25, 2379–2380, December 2003, 14681501, 10.1056/NEJMp038168, JOURNAL, Frieri M, Stampfl H, Systemic lupus erythematosus and atherosclerosis: Review of the literature, Autoimmunity Reviews, 15, 1, 16–21, January 2016, 26299985, 10.1016/j.autrev.2015.08.007, Steroids are sometimes prescribed as an anti-inflammatory treatment for lupus; however, they can increase one's risk for heart disease, high cholesterol, and atherosclerosis.WEB, Treating Lupus with Steroids,weblink Johns Hopkins Lupus Center, 1 December 2021,

Lungs

SLE can cause pleuritic pain as well as inflammation of the pleurae known as pleurisy, which can rarely give rise to shrinking lung syndrome involving a reduced lung volume.JOURNAL, Henderson LA, Loring SH, Gill RR, Liao KP, Ishizawar R, Kim S, Perlmutter-Goldenson R, Rothman D, Son MB, Stoll ML, Zemel LS, Sandborg C, Dellaripa PF, Nigrovic PA, Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies, The Journal of Rheumatology, 40, 3, 273–281, March 2013, 23378468, 4112073, 10.3899/jrheum.121048, JOURNAL, Calderaro DC, Ferreira GA, Presentation and prognosis of shrinking lung syndrome in systemic lupus erythematosus: report of four cases, Rheumatology International, 32, 5, 1391–1396, May 2012, 21431288, 10.1007/s00296-011-1863-5, 1955534, Other associated lung conditions include pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, and pulmonary hemorrhage.{{citation needed|date=September 2021}}

Kidneys

Painless passage of blood or protein in the urine may often be the only presenting sign of kidney involvement. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end-stage kidney failure. Because of early recognition and management of SLE with immunosuppressive drugs or corticosteroids,JOURNAL, Singh JA, Hossain A, Kotb A, Oliveira A, Mudano AS, Grossman J, Winthrop K, Wells GA, Treatments for Lupus Nephritis: A Systematic Review and Network Metaanalysis, The Journal of Rheumatology, 43, 10, 1801–1815, October 2016, 27585688, 10.3899/jrheum.160041, 19621372, free, end-stage renal failure occurs in less than 5%JOURNAL, Somers EC, Marder W, Cagnoli P, Lewis EE, DeGuire P, Gordon C, Helmick CG, Lu Wang (biostatistician), Wang L, Wing JJ, Dhar JP, Leisen J, Shaltis D, McCune WJ, Population-based incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program, Arthritis & Rheumatology, 66, 2, 369–378, February 2014, 24504809, 4198147, 10.1002/art.38238, 2027.42/102724, JOURNAL, Ward MM, Changes in the incidence of end-stage renal disease due to lupus nephritis, 1982-1995, Archives of Internal Medicine, 160, 20, 3136–3140, November 2000, 11074743, 10.1001/archinte.160.20.3136, free, of cases; except in the black population, where the risk is many times higher.The histological hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities.WEB,weblink General Pathology Images for Immunopathology, 2007-07-24,weblink" title="web.archive.org/web/20070510100001weblink">weblink 2007-05-10, This finding is due to immune complex deposition along the glomerular basement membrane, leading to a typical granular appearance in immunofluorescence testing.

Neuropsychiatric

{{Further|Neuropsychiatric systemic lupus erythematosus}}Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system. The American College of Rheumatology defines 19 neuropsychiatric syndromes in systemic lupus erythematosus.JOURNAL, The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes, Arthritis and Rheumatism, 42, 4, 599–608, April 1999, 10211873, 10.1002/1529-0131(199904)42:43.0.CO;2-F, free, The diagnosis of neuropsychiatric syndromes concurrent with SLE (now termed as NPSLE), is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke.JOURNAL, Neuwelt CM, Young RG, Managing neuropsychiatric lupus: Top 10 clinical pearls, The Journal of Musculoskeletal Medicine, 26, 4, April 2, 2009,weblinkweblink" title="web.archive.org/web/20090427042535weblink">weblink April 27, 2009, A common neurological disorder people with SLE have is headache,JOURNAL, Honczarenko K, Budzianowska A, Ostanek L, Neurological syndromes in systemic lupus erythematosus and their association with antiphospholipid syndrome, Neurologia I Neurochirurgia Polska, 42, 6, 513–517, 2008, 19235104,weblink 2009-03-07, 2020-01-07,weblink" title="web.archive.org/web/20200107200250weblink">weblink although the existence of a specific lupus headache and the optimal approach to headache in SLE cases remains controversial.JOURNAL, Omdal R, Some controversies of neuropsychiatric systemic lupus erythematosus, Scandinavian Journal of Rheumatology, 31, 4, 192–197, 2002, 12369649, 10.1080/030097402320318369, 1057841, Other common neuropsychiatric manifestations of SLE include cognitive disorder, mood disorder, cerebrovascular disease, seizures, polyneuropathy, anxiety disorder, psychosis, depression, and in some extreme cases, personality disorders.WEB,weblink Lupus site (SLE), 2009-11-06, live,weblink" title="web.archive.org/web/20100329044737weblink">weblink 2010-03-29, Steroid psychosis can also occur as a result of treating the disease.JOURNAL, Kasama T, Maeoka A, Oguro N, Clinical Features of Neuropsychiatric Syndromes in Systemic Lupus Erythematosus and Other Connective Tissue Diseases, Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders, 9, 1–8, 2016, 26819561, 4718090, 10.4137/CMAMD.S37477, It can rarely present with intracranial hypertension syndrome, characterized by an elevated intracranial pressure, papilledema, and headache with occasional abducens nerve paresis, absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid chemical and hematological constituents.JOURNAL, Xue Z, Wang X, Liu F, Hu S, Zhu S, Zhang S, Bu B, Intracranial hypertension syndrome in systemic lupus erythematosus: clinical analysis and review of the literature, Journal of Huazhong University of Science and Technology Medical Sciences, 29, 1, 107–111, February 2009, 19224175, 10.1007/s11596-009-0123-3, 195682502, More rare manifestations are acute confusional state, Guillain–Barré syndrome, aseptic meningitis, autonomic disorder, demyelinating syndrome, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder (more specifically, chorea), myasthenia gravis, myelopathy, cranial neuropathy and plexopathy.{{citation needed|date=September 2021}}Neurological disorders contribute to a significant percentage of morbidity and mortality in people with lupus.JOURNAL, West SG, Lupus and the central nervous system, Current Opinion in Rheumatology, 8, 5, 408–414, September 1996, 8941443, 10.1097/00002281-199609000-00004, As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. One aspect of this disease is severe damage to the epithelial cells of the blood–brain barrier. In certain regions, depression affects up to 60% of women with SLE.JOURNAL, Zakeri Z, Shakiba M, Narouie B, Mladkova N, Ghasemi-Rad M, Khosravi A, Prevalence of depression and depressive symptoms in patients with systemic lupus erythematosus: Iranian experience, Rheumatology International, 32, 5, 1179–1187, May 2012, 21253731, 10.1007/s00296-010-1791-9, 19597373,

Eyes

Up to one-third of patients report that their eyes are affected. The most common diseases are dry eye syndrome and secondary Sjögren's syndrome, but episcleritis, scleritis, retinopathy (more often affecting both eyes than one), ischemic optic neuropathy, retinal detachment, and secondary angle-closure glaucoma may occur. In addition, the medications used to treat SLE can cause eye disease: long-term glucocorticoid use can cause cataracts and secondary open-angle glaucoma, and long-term hydroxychloroquine treatment can cause vortex keratopathy and maculopathy.JOURNAL, Dammacco R, Systemic lupus erythematosus and ocular involvement: an overview, Clinical and Experimental Medicine, 18, 2, 135–149, May 2018, 29243035, 10.1007/s10238-017-0479-9, 13757311,

Reproductive

{{Further|Lupus and pregnancy}}While most pregnancies have positive outcomes, there is a greater risk of adverse events occurring during pregnancy.JOURNAL, Clowse ME, Lupus activity in pregnancy, Rheumatic Disease Clinics of North America, 33, 2, 237–52, v, May 2007, 17499705, 2745966, 10.1016/j.rdc.2007.01.002, SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in people with SLE has been estimated to be 72%.JOURNAL, Smyth A, Oliveira GH, Lahr BD, Bailey KR, Norby SM, Garovic VD, A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis, Clinical Journal of the American Society of Nephrology, 5, 11, 2060–2068, November 2010, 20688887, 3001786, 10.2215/CJN.00240110, Pregnancy outcome appears to be worse in people with SLE whose disease flares up during pregnancy.JOURNAL, Cortés-Hernández J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M, Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies, Rheumatology, 41, 6, 643–650, June 2002, 12048290, 10.1093/rheumatology/41.6.643, free, Neonatal lupus is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus, and sometimes with systemic abnormalities such as heart block or enlargement of the liver and spleen.thefreedictionary.com > neonatal lupus Citing: Dorland's Medical Dictionary for Health Consumers. Copyright 2007 Neonatal lupus is usually benign and self-limited.Medications for treatment of SLE can carry severe risks for female and male reproduction. Cyclophosphamide (also known as Cytoxan), can lead to infertility by causing premature ovarian insufficiency (POI), the loss of normal function of one's ovaries prior to age forty.WEB, Lupus and women's reproductive health {{!, Lupus Foundation of America |url=https://www.lupus.org/resources/womens-health-and-reproductive-issues-with-lupus |website=Lupus Foundation of America |access-date=1 December 2021 |language=en}} Methotrexate can cause termination or deformity in fetuses and is a common abortifacient, and for men taking a high dose and planning to father, a discontinuation period of 6 months is recommended before insemination.WEB, Methotrexate - Maxtrex, Metoject. Side effects and dosage,weblink 2022-06-30, patient.info, en,

Systemic

Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia or hypothyroidism, but also to pain, depression, poor sleep quality, poor physical fitness and lack of social support.JOURNAL, D'Cruz DP, Systemic lupus erythematosus, BMJ, 332, 7546, 890–894, April 2006, 16613963, 1440614, 10.1136/bmj.332.7546.890, JOURNAL, Jump RL, Robinson ME, Armstrong AE, Barnes EV, Kilbourn KM, Richards HB, Fatigue in systemic lupus erythematosus: contributions of disease activity, pain, depression, and perceived social support, The Journal of Rheumatology, 32, 9, 1699–1705, September 2005, 16142863,weblinkweblink" title="web.archive.org/web/20070816055540weblink">weblink 2007-08-16,

Causes

SLE is presumably caused by a genetic susceptibility coupled with an environmental trigger which results in defects in the immune system. One of the factors associated with SLE is vitamin D deficiency.JOURNAL, Schneider L, Dos Santos AS, Santos M, da Silva Chakr RM, Monticielo OA, Vitamin D and systemic lupus erythematosus: state of the art, Clinical Rheumatology, 33, 8, 1033–1038, August 2014, 24573738, 10.1007/s10067-014-2530-5, 28033436,

Genetics

SLE does run in families, but no single causal gene has been identified. Instead, multiple genes appear to influence a person's chance of developing lupus when triggered by environmental factors. HLA class I, class II, and class III genes are associated with SLE, but only classes I and II contribute independently to increased risk of SLE.JOURNAL, Martens HA, Nolte IM, van der Steege G, Schipper M, Kallenberg CG, Te Meerman GJ, Bijl M, An extensive screen of the HLA region reveals an independent association of HLA class I and class II with susceptibility for systemic lupus erythematosus, Scandinavian Journal of Rheumatology, 38, 4, 256–262, March 2009, 19255932, 10.1080/03009740802552469, 1514217, Other genes which contain risk variants for SLE are IRF5, PTPN22, STAT4,JOURNAL, Yang W, Ng P, Zhao M, Hirankarn N, Lau CS, Mok CC, Chan TM, Wong RW, Lee KW, Mok MY, Wong SN, Avihingsanon Y, Lee TL, Ho MH, Lee PP, Wong WH, Lau YL, Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese, Genes and Immunity, 10, 3, 219–226, April 2009, 19225526, 10.1038/gene.2009.1, 22026222, CDKN1A,JOURNAL, Kim K, Sung YK, Kang CP, Choi CB, Kang C, Bae SC, A regulatory SNP at position -899 in CDKN1A is associated with systemic lupus erythematosus and lupus nephritis, Genes and Immunity, 10, 5, 482–486, July 2009, 19262578, 10.1038/gene.2009.5, free, ITGAM, BLK, OX40L and BANK1.JOURNAL, Rhodes B, Vyse TJ, The genetics of SLE: an update in the light of genome-wide association studies, Rheumatology, 47, 11, 1603–1611, November 2008, 18611920, 10.1093/rheumatology/ken247, free, Some of the susceptibility genes may be population specific. Genetic studies of the rates of disease in families supports the genetic basis of this disease with a heritability of >66%.JOURNAL, Moser KL, Kelly JA, Lessard CJ, Harley JB, Recent insights into the genetic basis of systemic lupus erythematosus, Genes and Immunity, 10, 5, 373–379, July 2009, 19440199, 3144759, 10.1038/gene.2009.39, Identical (monozygotic) twins were found to share susceptibility to the disease at >35% rate compared to fraternal (dizygotic) twins and other full siblings who only showed a 2–5% concordance in shared inheritance.Since SLE is associated with many genetic regions, it is likely an oligogenic trait, meaning that there are several genes that control susceptibility to the disease.JOURNAL, Kelly JA, Moser KL, Harley JB, The genetics of systemic lupus erythematosus: putting the pieces together, Genes and Immunity, 3, Suppl 1, S71–S85, October 2002, 12215907, 10.1038/sj.gene.6363885, free, SLE is regarded as a prototype disease due to the significant overlap in its symptoms with other autoimmune diseases.JOURNAL, Prokunina L, Alarcon-Riquelme M, The genetic basis of systemic lupus erythematosus--knowledge of today and thoughts for tomorrow, Human Molecular Genetics, 13 Spec No 1, 90001, R143–R148, April 2004, 14764622, 10.1093/hmg/ddh076, free,

Drug reactions

Drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness. Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped. More than 38 medications can cause this condition, the most common of which are procainamide, isoniazid, hydralazine, quinidine, and phenytoin.WEB, Robert L. Rubin, Ph.D., Drug-Induced Lupus Erythematosus,weblinkweblink" title="web.archive.org/web/20061013065604weblink">weblink Lupus Foundation of America, 20 June 2018, 2006-10-13, (non-archive version no longer available),

Non-systemic forms of lupus

Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms. Approximately 5% of people with DLE progress to SLE.JOURNAL, Millard LG, Rowell NR, Abnormal laboratory test results and their relationship to prognosis in discoid lupus erythematosus. A long-term follow-up study of 92 patients, Archives of Dermatology, 115, 9, 1055–1058, September 1979, 314780, 10.1001/archderm.1979.04010090005011,

Pathophysiology

SLE is triggered by environmental factors that are unknown. In SLE, the body's immune system produces antibodies against self-protein, particularly against proteins in the cell nucleus. These antibody attacks are the immediate cause of SLE.JOURNAL, Rahman A, Isenberg DA, Systemic lupus erythematosus, The New England Journal of Medicine, 358, 9, 929–939, February 2008, 18305268, 10.1056/NEJMra071297, 10.1.1.1008.5428, JOURNAL, Crow MK, Collaboration, genetic associations, and lupus erythematosus, The New England Journal of Medicine, 358, 9, 956–961, February 2008, 18204099, 10.1056/NEJMe0800096, JOURNAL, Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, Lee AT, Chung SA, Ferreira RC, Pant PV, Ballinger DG, Kosoy R, Demirci FY, Kamboh MI, Kao AH, Tian C, Gunnarsson I, Bengtsson AA, Rantapää-Dahlqvist S, Petri M, Manzi S, Seldin MF, Rönnblom L, Syvänen AC, Criswell LA, Gregersen PK, Behrens TW, Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX, The New England Journal of Medicine, 358, 9, 900–909, February 2008, 18204098, 10.1056/NEJMoa0707865, 18987547, free, SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement.WEB,weblink University of South Carolina School of Medicine lecture notes, Immunology, Hypersensitivity reactions. General discussion of hypersensitivity, not specific to SLE, Pathmicro.med.sc.edu, 2010-07-07, 2011-08-06, live,weblink" title="web.archive.org/web/20110803082424weblink">weblink 2011-08-03, Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anti-cardiolipin antibodies, or a consequence of therapy.JOURNAL, Scheinfeld NS, DiCostanzo DD, Cohen SR, Reticulate and stellate acral pigmentation associated with systemic lupus erythematosus and high titers of circulating anticardiolipin antibodies: a possible association with acral microlivedo, Journal of Drugs in Dermatology, 2, 6, 674–676, December 2003, 14711150, People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased CD27+/IgD—are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BLyS), also known as B-cell activating factor (BAFF), interleukin 6, interleukin 17, interleukin 18, type I interferons, and tumor necrosis factor α (TNFα) are involved in the inflammatory process and are potential therapeutic targets.JOURNAL, Kanta H, Mohan C, Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral amplification by innate immunity and end-organ inflammation, Genes and Immunity, 10, 5, 390–396, July 2009, 19262576, 10.1038/gene.2009.6, 12936040, SLE is associated with low C3 levels in the complement system.WEB,weblink Complement C3 (Blood)—Health Encyclopedia—University of Rochester Medical Center, www.urmc.rochester.edu, live,weblink 2016-09-24,

Cell death signaling

• Apoptosis is increased in monocytes and keratinocytes
• Expression of Fas by B cells and T cells is increased
• There are correlations between the apoptotic rates of lymphocytes and disease activity.
• Necrosis is increased in T lymphocytes.

Tingible body macrophages (TBMs) â€“ large phagocytic cells in the germinal centers of secondary lymph nodes â€“ express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation. In some people with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells that may have randomly acquired self-protein specificity through somatic hypermutation.BOOK, Gaipl US, Kuhn A, Sheriff A, Munoz LE, Franz S, Voll RE, Kalden JR, Herrmann M, Elkon KB, Apoptosis and Its Relevance to Autoimmunity, Clearance of apoptotic cells in human SLE, Current Directions in Autoimmunity, 9, 173–187, 2006, 16394661, 978-3-8055-8036-6, Karger, 10.1159/000090781, Necrosis, a pro-inflammatory form of cell death, is increased in T lymphocytes, due to mitochondrial dysfunction, oxidative stress, and depletion of ATP.JOURNAL, Gergely P, Grossman C, Niland B, Puskas F, Neupane H, Allam F, Banki K, Phillips PE, Perl A, Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus, Arthritis and Rheumatism, 46, 1, 175–190, January 2002, 11817589, 4020417, 10.1002/1529-0131(200201)46:13.0.CO;2-H,

Clearance deficiency

(File:Picture1 englisch.jpg|thumb|Clearance deficiency)Impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes deficient phagocytic activity, impaired lysosomal degradation, and scant serum components in addition to increased apoptosis.{{Citation needed|date=March 2024}}SLE is associated with defects in apoptotic clearance, and the damaging effects caused by apoptotic debris. Early apoptotic cells express "eat-me" signals, of cell-surface proteins such as phosphatidylserine, that prompt immune cells to engulf them. Apoptotic cells also express find-me signals to attract macrophages and dendritic cells. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to the development of antinuclear antibodies.Monocytes isolated from whole blood of people with SLE show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the germinal centres of lymph nodes, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement factors, CRP, and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient.{{Citation needed|date=March 2024}}Macrophages during SLE fail to mature their lysosomes and as a result have impaired degradation of internalized apoptotic debris, which results in chronic activation of Toll-like receptors and permeabilization of the phagolysosomal membrane, allowing activation of cytosolic sensors. In addition, intact apoptotic debris recycles back to the cell membrane and accumulate on the surface of the cell.JOURNAL, Monteith AJ, Kang S, Scott E, Hillman K, Rajfur Z, Jacobson K, Costello MJ, Vilen BJ, Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus, Proceedings of the National Academy of Sciences of the United States of America, 113, 15, E2142–E2151, April 2016, 27035940, 4839468, 10.1073/pnas.1513943113, 2016PNAS..113E2142M, free, JOURNAL, Kang S, Rogers JL, Monteith AJ, Jiang C, Schmitz J, Clarke SH, Tarrant TK, Truong YK, Diaz M, Fedoriw Y, Vilen BJ, Apoptotic Debris Accumulates on Hematopoietic Cells and Promotes Disease in Murine and Human Systemic Lupus Erythematosus, Journal of Immunology, 196, 10, 4030–4039, May 2016, 27059595, 4868781, 10.4049/jimmunol.1500418, Recent research has found an association between certain people with lupus (especially those with lupus nephritis) and an impairment in degrading neutrophil extracellular traps (NETs). These were due to DNAse1 inhibiting factors, or NET protecting factors in people's serum, rather than abnormalities in the DNAse1 itself.JOURNAL, Hakkim A, Fürnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, Herrmann M, Voll RE, Zychlinsky A, Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis, Proceedings of the National Academy of Sciences of the United States of America, 107, 21, 9813–9818, May 2010, 20439745, 2906830, 10.1073/pnas.0909927107, free, 2010PNAS..107.9813H, DNAse1 mutations in lupus have so far only been found in some Japanese cohorts.JOURNAL, Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y, Mutation of DNASE1 in people with systemic lupus erythematosus, Nature Genetics, 28, 4, 313–314, August 2001, 11479590, 10.1038/91070, 21277651, The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens, as well as internal danger signals, inducing maturation of dendritic cells (DCs) since they have lost their membranes' integrity. Increased appearance of apoptotic cells also stimulates inefficient clearance. That leads to the maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules.JOURNAL, Gaipl US, Munoz LE, Grossmayer G, Lauber K, Franz S, Sarter K, Voll RE, Winkler T, Kuhn A, Kalden J, Kern P, Herrmann M, Clearance deficiency and systemic lupus erythematosus (SLE), Journal of Autoimmunity, 28, 2–3, 114–121, 2007, 17368845, 10.1016/j.jaut.2007.02.005, Autoimmunity possibly results from the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE).

Germinal centers

{{Unreferenced section|date=March 2024}}(File:Picture2 englisch.jpg|thumb|upright=1.4|Germinal centres in a person with SLE and controls (schematic). Red: CD68 in tingible body macrophages; black: TUNEL positive apoptotic cells. 1) Healthy donors with florid germinal centres show giant tingible body macrophages (TBM) containing ingested apoptotic cells and no uningested apoptotic cells outside the TBM. 2) People with follicular lymphoma show small tingible body macrophages (TBM) containing few ingested apoptotic cells however, there are no uningested apoptotic cells outside the TBM. 3) Some with SLE (1) show a lack of TBM and many uningested apoptotic cells decorating the surfaces of spindle-shaped cells, presumably follicular dendritic cells (SLE 1). 4) Some people with SLE show TBM containing few ingested apoptotic cells and many uningested apoptotic cells outside the TBM (SLE 2). However, about 50% of people with SLE show rather normal germinal centre.)In healthy conditions, apoptotic lymphocytes are removed in germinal centers (GC) by specialized phagocytes, the tingible body macrophages (TBM), which is why no free apoptotic and potential autoantigenic material can be seen. In some people with SLE, a buildup of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. Close to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow-derived DC, neither take it up nor present it via MHC molecules.Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into the germinal center light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC.This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells, a chronic autoimmune disease may be the consequence.

Anti-nRNP autoimmunity

Anti-nRNP autoantibodies to nRNP A and nRNP C initially targeted restricted, proline-rich motifs. Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.JOURNAL, Poole BD, Schneider RI, Guthridge JM, Velte CA, Reichlin M, Harley JB, James JA, Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus, Arthritis and Rheumatism, 60, 3, 848–859, March 2009, 19248110, 2653589, 10.1002/art.24306,

Others

Elevated expression of HMGB1 was found in the sera of people and mice with systemic lupus erythematosus, high mobility group box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its inflammatory and immune stimulating properties.JOURNAL, Pan HF, Wu GC, Li WP, Li XP, Ye DQ, High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus, Molecular Biology Reports, 37, 3, 1191–1195, March 2010, 19247800, 10.1007/s11033-009-9485-7, 7214396,

Diagnosis

File:Lupus band test.jpg|thumb|Micrograph of a section of human skin prepared for direct immunofluorescence using an anti-IgG antibody. The skin is from a person with systemic lupus erythematosus and shows IgG deposits at two different places. The first is a bandlike deposit along the epidermal basement membrane ("lupus band test" is positive); the second is within the nuclei of the epidermal cells (antinuclear antibodies are present).]]

Laboratory tests

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. ANA testing for lupus is highly sensitive, with the vast majority of individuals with Lupus testing positive; but the test is not specific, as a positive result may or may not be indicative of Lupus.JOURNAL, Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL, Jayne D, Cervera R, Costedoat-Chalumeau N, Diamond B, Gladman DD, Hahn B, Hiepe F, Jacobsen S, Khanna D, Lerstrøm K, Massarotti E, McCune J, Ruiz-Irastorza G, Sanchez-Guerrero J, Schneider M, Urowitz M, Bertsias G, Hoyer BF, Leuchten N, Tani C, Tedeschi SK, Touma Z, Schmajuk G, Anic B, Assan F, Chan TM, Clarke AE, Crow MK, Czirják L, Doria A, Graninger W, Halda-Kiss B, Hasni S, Izmirly PM, Jung M, Kumánovics G, Mariette X, Padjen I, Pego-Reigosa JM, Romero-Diaz J, Rúa-Figueroa Fernández Í, Seror R, Stummvoll GH, Tanaka Y, Tektonidou MG, Vasconcelos C, Vital EM, Wallace DJ, Yavuz S, Meroni PL, Fritzler MJ, Naden R, Dörner T, Johnson SR, 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus, Arthritis & Rheumatology, 71, 9, 1400–1412, September 2019, 31385462, 6827566, 10.1002/art.40930, Several techniques are used to detect ANAs. The most widely used is indirect immunofluorescence (IF). The pattern of fluorescence suggests the type of antibody present in the people's serum. Direct immunofluorescence can detect deposits of immunoglobulins and complement proteins in people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called lupus band test) is evidence of systemic lupus erythematosus.JOURNAL, Reich A, Marcinow K, Bialynicki-Birula R, The lupus band test in systemic lupus erythematosus patients, Therapeutics and Clinical Risk Management, 7, 27–32, January 2011, 21339940, 3039011, 10.2147/TCRM.S10145, free, ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE.Laboratory tests can also help distinguish between closely related connective tissue diseases. A multianalyte panel (MAP) of autoantibodies, including ANA, anti-dsDNA, and anti-Smith in combination with the measurement of cell-bound complement activation products (CB-CAPs) with an integrated algorithm has demonstrated 80% diagnostic sensitivity and 86% specificity in differentiating diagnosed SLE from other autoimmune connective tissue diseases.JOURNAL, Putterman C, Furie R, Ramsey-Goldman R, Askanase A, Buyon J, Kalunian K, Chatham WW, Massarotti E, Kirou K, Jordan N, Blanco I, Weinstein A, Chitkara P, Manzi S, Ahearn J, O'Malley T, Conklin J, Ibarra C, Barken D, Dervieux T, Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements, Lupus Science & Medicine, 1, 1, e000056, 2014, 25396070, 4225732, 10.1136/lupus-2014-000056, The MAP approach has been further studied in over 40,000 patients tested with either the MAP or traditional ANA testing strategy (tANA), demonstrating patients who test MAP positive are at up to 6-fold increased odds of receiving a new SLE diagnosis and up to 3-fold increased odds of starting a new SLE medication regimen as compared to patients testing positive with the tANA approach.JOURNAL, O'Malley T, Xie F, Su Y, Clinton C, Zack DJ, Haechung C, Grabner M, Curtis JR, Complement activation products vs standard ANA testing: Treatment outcomes, diagnosis, and economic impact (CAPSTONE) in systemic lupus erythematosus, Journal of Managed Care & Specialty Pharmacy, 28, 9, 1021–1032, September 2022, 35775579, 10.18553/jmcp.2022.22039, 250175290, The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in people with SLE are anti-U1 RNP (which also appears in systemic sclerosis and mixed connective tissue disease), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.JOURNAL, Buyon JP, Clancy RM, Maternal autoantibodies and congenital heart block: mediators, markers, and therapeutic approach, Seminars in Arthritis and Rheumatism, 33, 3, 140–154, December 2003, 14671725, 10.1016/j.semarthrit.2003.09.002, Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and kidney function (disturbed if the kidney is involved), liver enzymes, and complete blood count.{{Citation needed|date=March 2024}}The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cells are only found in 50–75% of SLE cases and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.WEB,weblinkweblink LE cell test, Medline Plus, U.S. National Library of Medicine, October 6, 2006,

Diagnostic criteria

Some physicians make a diagnosis based on the American College of Rheumatology (ACR) classification criteria. However, these criteria were primarily established for use in scientific research, including selection for randomized controlled trials, which require higher confidence levels. As a result, many people with SLE may not meet the full ACR criteria.{{Citation needed|date=March 2024}}

Criteria

The American College of Rheumatology (ACR) established eleven criteria in 1982,WEB,weblink Article on the classification of rheumatic diseases, Rheumatology.org, 2011-06-08, 2011-08-06, live,weblink" title="web.archive.org/web/20110718192030weblink">weblink 2011-07-18, which were revised in 1997WEB,weblink Revision of Rheumatology.org's diagnostic criteria, Rheumatology.org, 2011-06-08, 2011-08-06, live,weblink" title="web.archive.org/web/20110718192053weblink">weblink 2011-07-18, as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. For the purpose of identifying people for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions.

1. Malar rash (rash on cheeks); sensitivity = 57%; specificity = 96%.
2. Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%.
3. Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific).
4. Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%; specificity = 96%.
5. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%.
6. Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%.
7. Blood—hematologic disorder—hemolytic anemia (low red blood cell count), leukopenia (white blood cell count