View source for Medicine:Systemic lupus erythematosus

{{short description|Human autoimmune disease}}
{{pp-semi-indef}}
{{Infobox medical condition (new)
| name            = Systemic lupus erythematosus
| synonyms        = Lupus
| image           = Lupusfoto.jpg
| caption         = Young woman with the typical "butterfly rash" found in lupus
| field           = [[Medicine:Rheumatology|Rheumatology]]
| pronounce       = {{IPAc-en|audio=Systemic lupus erythematosus pronunciation.ogg|s|ɪ|ˈ|s|t|ɛ|m|ɪ|k|_|ˈ|l|uː|p|ə|s|_|ˌ|ɛr|ɪ|θ|iː|m|ə|ˈ|t|oʊ|s|ə|s}} {{respell|sih|STEM|ik|_|LOOP|əs|_|ERR|i|thee|mə|TOH|səs}}
| symptoms        = [[Medicine:Arthritis|Painful and swollen joints]], [[Medicine:Fever|fever]], [[Medicine:Chest pain|chest pain]], [[Medicine:Hair loss|hair loss]], mouth ulcers, swollen lymph nodes, feeling tired, red rash<ref name=NIH2015/>
| complications   = 
| onset           = 15–45 years of age<ref name=NIH2015/><ref name=Dan2006/>
| duration        = Long term<ref name=NIH2015/>
| causes          = Unclear<ref name=NIH2015/>
| risks           = 
| diagnosis       = Based on symptoms and blood tests<ref name=NIH2015/>
| differential    = 
| prevention      = 
| treatment       = 
| medication      = NSAIDs, [[Biology:Corticosteroid|corticosteroid]]s, [[Chemistry:Immunosuppressive drug|immunosuppressants]], [[Chemistry:Hydroxychloroquine|hydroxychloroquine]], [[Chemistry:Methotrexate|methotrexate]]<ref name=NIH2015/>
| prognosis       = 15 year survival ~80%<ref name=Cle2012/>
| frequency       = 2–7 per 10,000<ref name=Dan2006/>
| deaths          = 
}}
<!-- Definition and symptoms -->
'''Systemic lupus erythematosus''' ('''SLE'''), also known simply as '''lupus''', is an [[Medicine:Autoimmune disease|autoimmune disease]] in which the body's [[Biology:Immune system|immune system]] mistakenly attacks healthy tissue in many parts of the body.<ref name=NIH2015>{{cite web|title=Handout on Health: Systemic Lupus Erythematosus|url=http://www.niams.nih.gov/health_info/Lupus/default.asp|website=www.niams.nih.gov|accessdate=12 June 2016|date=February 2015|url-status=live|archiveurl=https://web.archive.org/web/20160617162703/http://www.niams.nih.gov/Health_Info/Lupus/default.asp|archivedate=17 June 2016}}</ref> Symptoms vary between people and may be mild to severe.<ref name=NIH2015/> Common symptoms include [[Medicine:Arthritis|painful and swollen joints]], [[Medicine:Fever|fever]], [[Medicine:Chest pain|chest pain]], [[Medicine:Hair loss|hair loss]], mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face.<ref name=NIH2015/> Often there are periods of illness, called flares, and periods of [[Medicine:Remission|remission]] during which there are few symptoms.<ref name=NIH2015/>

<!-- Cause and diagnosis -->
The cause of SLE is not clear.<ref name=NIH2015/> It is thought to involve genetics together with environmental factors.<ref name=Lancet2014/> Among [[Biology:Twin study|identical twins]], if one is affected there is a 24% chance the other one will be as well.<ref name=NIH2015/> [[Biology:Sex steroid|Female sex hormones]], sunlight, smoking, [[Medicine:Vitamin D deficiency|vitamin D deficiency]], and certain infections, are also believed to increase the risk.<ref name=Lancet2014/> The mechanism involves an immune response by [[Biology:Autoantibody|autoantibodies]] against a person's own tissues.<ref name=NIH2015/> These are most commonly [[Biology:Anti-nuclear antibody|anti-nuclear antibodies]] and they result in [[Medicine:Inflammation|inflammation]].<ref name=NIH2015/> Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests.<ref name=NIH2015/> There are a number of other kinds of [[Medicine:Lupus erythematosus|lupus erythematosus]] including [[Medicine:Discoid lupus erythematosus|discoid lupus erythematosus]], neonatal lupus, and subacute cutaneous lupus erythematosus.<ref name=NIH2015/>

<!-- Treatment and prognosis -->
There is no cure for SLE.<ref name=NIH2015/> Treatments may include NSAIDs, [[Biology:Corticosteroid|corticosteroid]]s, [[Chemistry:Immunosuppressive drug|immunosuppressants]], [[Chemistry:Hydroxychloroquine|hydroxychloroquine]], and [[Chemistry:Methotrexate|methotrexate]].<ref name=NIH2015/> Although corticosteroids are rapidly effective, long term use results in side effects.<ref>{{cite journal |last1=Davis |first1=Laurie S. |last2=Reimold |first2=Andreas M. |title=Research and therapeutics—traditional and emerging therapies in systemic lupus erythematosus |journal=Rheumatology |date=April 2017 |volume=56 |issue=suppl_1 |pages=i100–i113 |doi=10.1093/rheumatology/kew417|pmid=28375452 |pmc=5850311 }}</ref> [[Medicine:Alternative medicine|Alternative medicine]] has not been shown to affect the disease.<ref name=NIH2015/> Life expectancy is lower among people with SLE.<ref name=Murphy2013>{{cite journal|last1=Murphy|first1=G|last2=Isenberg|first2=D|title=Effect of gender on clinical presentation in systemic lupus erythematosus.|journal=Rheumatology (Oxford, England)|date=December 2013|volume=52|issue=12|pages=2108–15|pmid=23641038|doi=10.1093/rheumatology/ket160}}</ref> SLE significantly increases the risk of [[Medicine:Cardiovascular disease|cardiovascular disease]] with this being the most common cause of death.<ref name=Lancet2014/> With modern treatment about 80% of those affected survive more than 15 years.<ref name=Cle2012>{{cite book|title=The Cleveland Clinic Intensive Review of Internal Medicine|date=2012|publisher=Lippincott Williams & Wilkins|isbn=9781451153309|page=969|edition=5|url=https://books.google.com/books?id=4LeX_5Vwy-4C&pg=PA969|accessdate=13 June 2016}}</ref> Women with lupus have pregnancies that are higher risk but are mostly successful.<ref name=NIH2015/>

<!-- Epidemiology and history -->
Rate of SLE varies between countries from 20 to 70 per 100,000.<ref name=Dan2006/> Women of childbearing age are affected about nine times more often than men.<ref name=Lancet2014>{{cite journal|last1=Lisnevskaia|first1=L|last2=Murphy|first2=G|last3=Isenberg|first3=D|title=Systemic lupus erythematosus.|journal=Lancet|date=22 November 2014|volume=384|issue=9957|pages=1878–88|pmid=24881804|doi=10.1016/s0140-6736(14)60128-8|citeseerx=10.1.1.1008.5428}}</ref> While it most commonly begins between the ages of 15 and 45, a wide range of ages can be affected.<ref name=NIH2015/><ref name=Dan2006>{{cite journal|last1=Danchenko|first1=N.|last2=Satia|first2=J.A.|last3=Anthony|first3=M.S.|title=Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden|journal=Lupus|date=2006|volume=15|issue=5|pages=308–318|doi=10.1191/0961203306lu2305xx|pmid=16761508}}</ref> Those of African, Caribbean, and Chinese descent are at higher risk than [[Biography:White people|white people]].<ref name=Lancet2014/><ref name=Dan2006/> Rates of disease in the developing world are unclear.<ref name=Tif2013>{{cite journal|last1=Tiffin|first1=N|last2=Adeyemo|first2=A|last3=Okpechi|first3=I|title=A diverse array of genetic factors contribute to the pathogenesis of systemic lupus erythematosus.|journal=Orphanet Journal of Rare Diseases|date=7 January 2013|volume=8|pages=2|pmid=23289717|doi=10.1186/1750-1172-8-2|pmc=3551738}}</ref> 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.<ref name=Chab2013>{{cite book|last1=Chabner|first1=Davi-Ellen|title=The Language of Medicine|date=2013|publisher=Elsevier Health Sciences|isbn=978-1455728466|page=610|url=https://books.google.com/books?id=OUAD3KKPRwIC&pg=PA610}}</ref>

==Signs and symptoms==
[[File:Symptoms of SLE.png|thumb|Common symptoms of SLE<ref>[http://www.medicinenet.com/systemic_lupus/page2.htm#3whatcauses MedicineNet: Systemic Lupus (cont.)] {{webarchive|url=https://web.archive.org/web/20091220005309/http://www.medicinenet.com/systemic_lupus/page2.htm |date=2009-12-20 }} Last Editorial Review: 2009-01-30</ref>]]

SLE is one of several diseases known as "the great imitator" because it often mimics or is mistaken for other illnesses.<ref>{{cite web|url=http://healthcare.utah.edu/healthtools/articles/lupus.html |title=Lupus, "The Great Imitator" |publisher=University Health Care |accessdate=2009-02-03 |url-status=dead |archiveurl=https://web.archive.org/web/20090115100021/http://healthcare.utah.edu/healthtools/articles/lupus.html |archivedate=January 15, 2009 }}</ref> SLE is a classical item in [[Medicine:Differential diagnosis|differential diagnosis]],<ref name="rahman"/> 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.

Common initial and [[Medicine:Chronic condition|chronic]] complaints include [[Medicine:Fever|fever]], malaise, [[Medicine:Arthralgia|joint pains]], [[Medicine:Myalgia|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.<ref name=mayo_lupussymptoms>{{cite web|title=Lupus: Symptoms&nbsp;— MayoClinic.com|url=http://www.mayoclinic.com/health/lupus/DS00115/DSECTION=symptoms|accessdate=2008-07-14|url-status=live|archiveurl=https://web.archive.org/web/20080714123532/http://www.mayoclinic.com/health/lupus/DS00115/DSECTION%3Dsymptoms|archivedate=2008-07-14}}</ref>

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.<ref name = Murphy2013 /> Females tend to have a greater number of relapses, a [[Medicine:Leukopenia|low white blood cell count]], more [[Medicine:Arthritis|arthritis]], Raynaud's phenomenon, and [[Medicine:Mental disorder|psychiatric symptoms]]. Males tend to have more [[Medicine:Seizure|seizure]]s, [[Medicine:Kidney disease|kidney disease]], serositis (inflammation of tissues lining the lungs and heart), skin problems, and [[Medicine:Peripheral neuropathy|peripheral neuropathy]].<ref name=":3">{{Cite journal |pmid=16115579|doi=10.1016/S1550-8579(04)80006-8|title=Gender differences in systemic lupus erythematosus|journal=Gender Medicine|volume=1|issue=1|pages=12–17|year=2004|last1=Yacoub Wasef|first1=Sherif Z.}}</ref>

===Skin===
As 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 [[Medicine:Discoid lupus erythematosus|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 (or ''butterfly rash'') associated with the disease.<ref>{{cite journal |last1=Tebbe |first1=B |last2=Orfanos |first2=CE |title=Epidemiology and socioeconomic impact of skin disease in lupus erythematosus |journal=Lupus |date=1997 |volume=6 |issue=2 |doi=10.1177/096120339700600204 |pmid=9061657 |pages=96–104}}</ref> This rash occurs in 30 to 60% of people with SLE.<ref>{{cite book |editor1-first=Jeffrey P. |editor1-last=Harris |editor2-first=Michael H. |editor2-last=Weisman |title=Head and neck manifestations of systemic disease |date=2007 |publisher=Informa Healthcare |location=New York |isbn=9781420017564 |page=6 |url=https://books.google.com/books?id=31yUl-V90XoC&pg=PA6 }}</ref>

Hair loss, mouth and nasal ulcers, and lesions on the skin are other possible manifestations.<ref name="UpToDateSLE">{{cite web|last1=Gladman|first1=Dafna|title=Overview of the clinical manifestations of systemic lupus erythematosus in adults|url=https://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-systemic-lupus-erythematosus-in-adults|website=UpToDate|accessdate=18 April 2017|date=10 September 2015|url-access=subscription |url-status=live|archiveurl=https://web.archive.org/web/20170419003102/https://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-systemic-lupus-erythematosus-in-adults|archivedate=19 April 2017}}</ref>

===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.<ref name="lfa1">[http://www.lupus.org/webmodules/webarticlesnet/templates/new_aboutaffects.aspx?articleid=99&zoneid=17 Joint and Muscle Pain] {{webarchive|url=https://web.archive.org/web/20071109161325/http://www.lupus.org/webmodules/webarticlesnet/templates/new_aboutaffects.aspx?articleid=99&zoneid=17 |date=2007-11-09 }} Lupus Foundation of America</ref> Unlike [[Medicine:Rheumatoid arthritis|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.<ref name="lfa1"/> People with SLE are at particular risk of developing osteoarticular [[Medicine:Tuberculosis|tuberculosis]].<ref name="pmid19246552">{{cite journal |vauthors=Hodkinson B, Musenge E, Tikly M |title=Osteoarticular tuberculosis in patients with systemic lupus erythematosus |journal=QJM |volume= 102|issue= 5|pages= 321–8|date=February 2009 |pmid=19246552 |doi=10.1093/qjmed/hcp015 }}</ref>

A possible association between [[Medicine:Rheumatoid arthritis|rheumatoid arthritis]] and SLE has been suggested,<ref name="pmid19248111">{{cite journal |vauthors=Hemminki K, Li X, Sundquist J, Sundquist K |title=Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions |journal=Arthritis Rheum. |volume=60 |issue=3 |pages=661–8 |date=February 2009 |pmid=19248111 |doi=10.1002/art.24328}}</ref> and SLE may be associated with an increased risk of [[Medicine:Bone fracture|bone fracture]]s in relatively young women.<ref name="pmid19224131">{{cite journal |vauthors=Mendoza-Pinto C, García-Carrasco M, Sandoval-Cruz H, etal |title=Risk factors of vertebral fractures in women with systemic lupus erythematosus |journal=Clin. Rheumatol. |volume= 28|issue= 5|pages= 579–85|date=February 2009 |pmid=19224131 |doi=10.1007/s10067-009-1105-3}}</ref>

===Blood===
[[Medicine:Anemia|Anemia]] is common in children with SLE<ref name="pmid2133750">{{cite journal|last=Lam|first=SK|author2=Quah, TC |title=Anemia in systemic lupus erythematosus.|journal=The Journal of the Singapore Paediatric Society|year=1990|volume=32|issue=3–4|pages=132–6|pmid=2133750}}</ref> and develops in about 50% of cases.<ref name="pmid16079164">{{cite journal|last=Giannouli|first=S|title=Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment|journal=Annals of the Rheumatic Diseases|date=1 February 2006|volume=65|issue=2|pages=144–148|doi=10.1136/ard.2005.041673|pmid=16079164|pmc=1798007}}</ref> [[Medicine:Thrombocytopenia|Low platelet count]] and [[Medicine:Leukopenia|white blood cell count]] may be due to the disease or a side effect of pharmacological treatment. People with SLE may have an association with [[Medicine:Antiphospholipid syndrome|antiphospholipid antibody syndrome]]<ref name="pmid19224124">{{cite journal |vauthors=Syuto T, Shimizu A, Takeuchi Y, etal |title=Association of antiphosphatidylserine/prothrombin antibodies with neuropsychiatric systemic lupus erythematosus |journal=Clin. Rheumatol. |volume= 28|issue= 7|pages= 841–5|date=February 2009 |pmid=19224124 |doi=10.1007/s10067-009-1123-1}}</ref> (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged [[Medicine:Partial thromboplastin time|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 [[Medicine:Syphilis|syphilis]].{{citation needed|date=September 2011}}

===Heart===
SLE may cause [[Medicine:Pericarditis|pericarditis]]—inflammation of the outer lining surrounding the heart, [[Medicine:Myocarditis|myocarditis]]—inflammation of the heart muscle, or [[Medicine:Endocarditis|endocarditis]]—inflammation of the inner lining of the heart. The endocarditis of SLE is non-infectious, and is also called ([[Medicine:Libman–Sacks endocarditis|Libman–Sacks endocarditis]]). It involves either the mitral valve or the tricuspid valve. [[Medicine:Atherosclerosis|Atherosclerosis]] also occurs more often and advances more rapidly than in the general population.<ref>{{cite journal | author=Bevra Hannahs Hahn, M.D. | title=Systemic lupus erythematosus and accelerated atherosclerosis | journal=N Engl J Med | volume=349 | date=December 2003 | pages=2379–80 | pmid=14681501 | doi=10.1056/NEJMp038168 | issue=25 }}</ref><ref>{{cite journal|last1=Frieri|first1=M|last2=Stampfl|first2=H|title=Systemic lupus erythematosus and atherosclerosis: Review of the literature.|journal=Autoimmunity Reviews|date=January 2016|volume=15|issue=1|pages=16–21|pmid=26299985|doi=10.1016/j.autrev.2015.08.007}}</ref>

===Lungs===
SLE can cause pleuritic pain as well as inflammation of the pleurae known as [[Medicine:Pleurisy|pleurisy]], which can rarely give rise to shrinking lung syndrome involving a reduced lung volume.<ref name="SLS">{{cite journal|last1=Henderson|first1=LA|last2=Loring|first2=SH|last3=Gill|first3=RR|last4=Liao|first4=KP|last5=Ishizawar|first5=R|last6=Kim|first6=S|last7=Perlmutter-Goldenson|first7=R|last8=Rothman|first8=D|last9=Son|first9=MB|last10=Stoll|first10=ML|last11=Zemel|first11=LS|last12=Sandborg|first12=C|last13=Dellaripa|first13=PF|last14=Nigrovic|first14=PA|title=Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.|journal=The Journal of Rheumatology|date=March 2013|volume=40|issue=3|pages=273–81|pmid=23378468|doi=10.3899/jrheum.121048|pmc=4112073}}</ref><ref name="Ferreira">{{cite journal|last1=Calderaro|first1=DC|last2=Ferreira|first2=GA|title=Presentation and prognosis of shrinking lung syndrome in systemic lupus erythematosus: report of four cases.|journal=Rheumatology International|date=May 2012|volume=32|issue=5|pages=1391–6|pmid=21431288|doi=10.1007/s00296-011-1863-5}}</ref> Other associated lung conditions include [[Medicine:Pneumonitis|pneumonitis]], chronic diffuse [[Medicine:Interstitial lung disease|interstitial lung disease]], [[Medicine:Pulmonary hypertension|pulmonary hypertension]], [[Medicine:Pulmonary embolism|pulmonary emboli]], and [[Medicine:Pulmonary hemorrhage|pulmonary hemorrhage]].

===Kidneys===
Painless passage of [[Medicine:Hematuria|blood]] or protein in the urine may often be the only presenting sign of kidney involvement. Acute or chronic renal impairment may develop with [[Medicine:Lupus nephritis|lupus nephritis]], leading to acute or end-stage [[Medicine:Kidney failure|kidney failure]]. Because of early recognition and management of SLE, end-stage renal failure occurs in less than 5%<ref name="pmid24504809">{{cite journal|vauthors=Somers EC, Marder W, Cagnoli P, Lewis EE, DeGuire P, Gordon C, etal | title=Population-based incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program. | journal=Arthritis Rheumatol | year= 2014 | volume= 66 | issue= 2 | pages= 369–78 | pmid=24504809 | doi=10.1002/art.38238 | pmc=4198147| url=https://deepblue.lib.umich.edu/bitstream/2027.42/106579/1/Somers_AandR%202014_MILES%20SLE%20inc%20prev.pdf | hdl=2027.42/102724 }}</ref><ref name="pmid11074743">{{cite journal| author=Ward MM| title=Changes in the incidence of end-stage renal disease due to lupus nephritis, 1982–1995. | journal=Arch Intern Med | year= 2000 | volume= 160 | issue= 20 | pages= 3136–40 | pmid=11074743 | doi=10.1001/archinte.160.20.3136}}</ref> of cases; except in the black population, where the risk is many times higher.

The histological hallmark of SLE is membranous [[Medicine:Glomerulonephritis|glomerulonephritis]] with "wire loop" abnormalities.<ref>{{cite web |url=http://erl.pathology.iupui.edu/C603/GENE607.HTM |title=General Pathology Images for Immunopathology |accessdate=2007-07-24 |url-status=dead |archiveurl=https://web.archive.org/web/20070510100001/http://erl.pathology.iupui.edu/C603/GENE607.HTM |archivedate=2007-05-10 }}</ref> This finding is due to immune complex deposition along the glomerular basement membrane, leading to a typical granular appearance in [[Biology:Immunofluorescence|immunofluorescence]] testing.

===Neuropsychiatric===
{{Further|Medicine:Neuropsychiatric systemic lupus erythematosus}}
[[Biology:Neuropsychiatry|Neuropsychiatric]] syndromes can result when SLE affects the [[Biology:Central nervous system|central]] or [[Biology:Peripheral nervous system|peripheral nervous system]]. The American College of Rheumatology defines 19 neuropsychiatric syndromes in systemic lupus erythematosus.<ref name="pmid10211873">{{cite journal |title=The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes |journal=Arthritis Rheum. |volume=42 |issue=4 |pages=599–608 |date=April 1999 |pmid=10211873 |doi=10.1002/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F }}</ref> The diagnosis of neuropsychiatric syndromes concurrent with SLE (now termed as NPSLE),<ref name="Kasama"/> 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.<ref>{{cite journal|vauthors=Neuwelt CM, Young RG|title=Managing neuropsychiatric lupus: Top 10 clinical pearls |journal=The Journal of Musculoskeletal Medicine |volume=26 |issue=4 |date=April 2, 2009 |url=http://jmm.consultantlive.com/display/article/1145622/1396901 |url-status=dead |archiveurl=https://web.archive.org/web/20090427042535/http://jmm.consultantlive.com/display/article/1145622/1396901 |archivedate=April 27, 2009 }}</ref>

A common [[Medicine:Neurological disorder|neurological disorder]] people with SLE have is [[Medicine:Headache|headache]],<ref name="pmid19235104">{{cite journal |vauthors=Honczarenko K, Budzianowska A, Ostanek L |title=Neurological syndromes in systemic lupus erythematosus and their association with antiphospholipid syndrome |journal=Neurol. Neurochir. Pol. |volume=42 |issue=6 |pages=513–7 |year=2008 |pmid=19235104 |url=http://www.neurology.termedia.pl/showarticle.php?id=11794 }}</ref> although the existence of a specific [[Medicine:Lupus headache|lupus headache]] and the optimal approach to headache in SLE cases remains controversial.<ref name="pmid12369649">{{cite journal |author=Omdal R |title=Some controversies of neuropsychiatric systemic lupus erythematosus |journal=Scand. J. Rheumatol. |volume=31 |issue=4 |pages=192–7 |year=2002 |pmid=12369649 |doi= 10.1080/030097402320318369}}</ref>
Other common neuropsychiatric manifestations of SLE include cognitive dysfunction, [[Medicine:Mood disorder|mood disorder]], cerebrovascular disease,<ref name="pmid19235104"/> seizures, [[Medicine:Polyneuropathy|polyneuropathy]],<ref name="pmid19235104"/> [[Medicine:Anxiety disorder|anxiety disorder]], [[Medicine:Psychosis|psychosis]], [[Medicine:Depression (mood)|depression]], and in some extreme cases, personality disorders.<ref>{{cite web |url=http://www.uklupus.co.uk/fact5.html |title=Lupus site (SLE) |accessdate=2009-11-06 |url-status=live |archiveurl=https://web.archive.org/web/20100329044737/http://www.uklupus.co.uk/fact5.html |archivedate=2010-03-29 }}</ref> [[Chemistry:Anabolic steroid|Steroid psychosis]] can also occur as a result of treating the disease.<ref name="Kasama">{{cite journal|last1=Kasama|first1=T|last2=Maeoka|first2=A|last3=Oguro|first3=N|title=Clinical Features of Neuropsychiatric Syndromes in Systemic Lupus Erythematosus and Other Connective Tissue Diseases.|journal=Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders| date=2016| volume=9| pages=1–8| pmid=26819561| doi=10.4137/CMAMD.S37477|pmc=4718090}}</ref> It can rarely present with [[Medicine:Intracranial hypertension syndrome|intracranial hypertension syndrome]], characterized by an elevated [[Medicine:Intracranial pressure|intracranial pressure]], papilledema, and [[Medicine:Headache|headache]] with occasional abducens [[Biology:Nerve|nerve]] [[Medicine:Paresis|paresis]], absence of a space-occupying lesion or ventricular enlargement, and normal [[Biology:Cerebrospinal fluid|cerebrospinal fluid]] chemical and hematological constituents.<ref name="pmid19224175">{{cite journal |vauthors=Xue Z, Wang X, Liu F, etal |title=Intracranial hypertension syndrome in systemic lupus erythematosus: Clinical analysis and review of the literature |journal=J. Huazhong Univ. Sci. Technol. Med. Sci. |volume=29 |issue=1 |pages=107–11 |date=February 2009 |pmid=19224175 |doi=10.1007/s11596-009-0123-3}}</ref>

More rare manifestations are [[Medicine:Delirium|acute confusional state]], [[Medicine:Guillain–Barré syndrome|Guillain–Barré syndrome]], aseptic meningitis, [[Medicine:Autonomic neuropathy|autonomic disorder]], [[Medicine:Demyelinating disease|demyelinating syndrome]], mononeuropathy (which might manifest as mononeuritis multiplex), [[Medicine:Movement disorder|movement disorder]] (more specifically, chorea), [[Medicine:Myasthenia gravis|myasthenia gravis]], myelopathy, cranial neuropathy and [[Medicine:Plexopathy|plexopathy]].

Neurological disorders contribute to a significant percentage of morbidity and mortality in people with lupus.<ref name="West-1996">{{cite journal |author=West SG |title=Lupus and the central nervous system |journal=Curr Opin Rheumatol |volume=8 |issue=5 |pages=408–14 |date=September 1996 |pmid=8941443 |doi=10.1097/00002281-199609000-00004}}</ref> As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates.<ref name="pmid10211873"/> One aspect of this disease is severe damage to the epithelial cells of the [[Biology:Blood–brain barrier|blood–brain barrier]]. In certain regions, depression affects up to 60% of women with SLE.<ref>{{cite journal |vauthors=Zakeri Z, Shakiba M, Narouie B, Mladkova N, Ghasemi-Rad M, Khosravi A |title=Prevalence of depression and depressive symptoms in patients with systemic lupus erythematosus: Iranian experience |journal=Rheumatol Int |date=January 2011 |pmid=21253731 |doi=10.1007/s00296-010-1791-9 |volume=32 |issue=5 |pages=1179–87}}</ref>

=== Eyes ===
Eye involvement is seen in up to one-third of people. The most common diseases are [[Medicine:Dry eye syndrome|dry eye syndrome]] and secondary [[Medicine:Sjögren syndrome|Sjögren's syndrome]], but [[Medicine:Episcleritis|episcleritis]], [[Medicine:Scleritis|scleritis]], [[Medicine:Retinopathy|retinopathy]] (more often affecting both eyes than one), ischemic optic neuropathy, [[Medicine:Retinal detachment|retinal detachment]], and [[Medicine:Glaucoma|secondary angle-closure glaucoma]] may occur. In addition, the medications used to treat SLE can cause eye disease: long-term [[Chemistry:Glucocorticoid|glucocorticoid]] use can cause [[Medicine:Cataract|cataract]]s and secondary open-angle glaucoma, and long-term [[Chemistry:Hydroxychloroquine|hydroxychloroquine]] treatment can cause [[Medicine:Cornea verticillata|vortex keratopathy]] and [[Medicine:Maculopathy|maculopathy]].<ref>{{Cite journal|last=Dammacco|first=Rosanna|date=May 2018|title=Systemic lupus erythematosus and ocular involvement: an overview|journal=Clinical and Experimental Medicine|volume=18|issue=2|pages=135–149|doi=10.1007/s10238-017-0479-9|issn=1591-9528|pmid=29243035}}</ref>

===Reproductive===
While most pregnancies have positive outcomes there is a greater risk of adverse events occurring during pregnancy.<ref>{{cite journal |last1=Clowse |first1=ME |title=Lupus activity in pregnancy. |journal=Rheumatic Diseases Clinics of North America |date=May 2007 |volume=33 |issue=2 |pages=237–52, v |doi=10.1016/j.rdc.2007.01.002 |pmid=17499705|pmc=2745966 }}</ref> 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%.<ref>{{cite journal|last=Smyth|first=Andrew|author2=Guilherme H.M. Oliveira|author3=Brian D. Lahr|author4=Kent R. Bailey|author5=Suzanne M. Norby|author6=Vesna D. Garovic|title=A Systematic Review and Meta-Analysis of Pregnancy Outcomes in Patients with Systemic Lupus Erythematosus and Lupus Nephritis|journal=Clinical Journal of the American Society of Nephrology|date=November 2010|volume=5|issue=11|pages=2060–2068|doi=10.2215/CJN.00240110|url=http://cjasn.asnjournals.org/content/5/11/2060.abstract|pmid=20688887|pmc=3001786|url-status=live|archiveurl=https://web.archive.org/web/20160126141220/http://cjasn.asnjournals.org/content/5/11/2060.abstract|archivedate=2016-01-26}}</ref> Pregnancy outcome appears to be worse in people with SLE whose disease flares up during pregnancy.<ref>{{cite journal|last=Cortés‐Hernández|first=J.|first2=J.|last2=Ordi‐Ros|first3=F.|last3=Paredes|first4=M.|last4=Casellas|first5=F.|last5=Castillo|first6=M.|last6=Vilardell‐Tarres|title=Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies|journal=Rheumatology|date=December 2001|volume=41|issue=6|pages=643–650|doi=10.1093/rheumatology/41.6.643|pmid=12048290}}</ref>

Neonatal lupus is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling [[Medicine:Discoid lupus erythematosus|discoid lupus erythematosus]], and sometimes with systemic abnormalities such as [[Medicine:Heart block|heart block]] or [[Medicine:Hepatosplenomegaly|enlargement of the liver and spleen]].<ref name=Dorlands>[http://medical-dictionary.thefreedictionary.com/neonatal+lupus thefreedictionary.com &gt; neonatal lupus] Citing: Dorland's Medical Dictionary for Health Consumers. Copyright 2007</ref> Neonatal lupus is usually benign and self-limited.<ref name=Dorlands/>

===Systemic===
Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as [[Medicine:Anemia|anemia]] or [[Medicine:Hypothyroidism|hypothyroidism]], but also to [[Medicine:Pain|pain]], depression, poor [[Biology:Sleep|sleep]] quality, poor physical fitness and lack of [[Social:Social support|social support]].<ref name="pmid16613963">{{cite journal |author=D'Cruz DP |title=Systemic lupus erythematosus |journal=BMJ |volume=332 |issue=7546 |pages=890–4 |date=April 2006 |pmid=16613963 |pmc=1440614 |doi=10.1136/bmj.332.7546.890 }}</ref><ref name="pmid16142863">{{cite journal |vauthors=Jump RL, Robinson ME, Armstrong AE, Barnes EV, Kilbourn KM, Richards HB |title=Fatigue in systemic lupus erythematosus: contributions of disease activity, pain, depression, and perceived social support |journal=J. Rheumatol. |volume=32 |issue=9 |pages=1699–705 |date=September 2005 |pmid=16142863 |url=http://www.jrheum.com/subscribers/05/09/1699.html |url-status=dead |archiveurl=https://web.archive.org/web/20070816055540/http://www.jrheum.com/subscribers/05/09/1699.html |archivedate=2007-08-16 }}</ref>

==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 [[Medicine:Vitamin D deficiency|vitamin D deficiency]].<ref>{{cite journal|last1=Schneider|first1=L|last2=Dos Santos|first2=AS|last3=Santos|first3=M|last4=da Silva Chakr|first4=RM|last5=Monticielo|first5=OA|title=Vitamin D and systemic lupus erythematosus: state of the art.|journal=Clinical Rheumatology|date=August 2014|volume=33|issue=8|pages=1033–8|pmid=24573738|doi=10.1007/s10067-014-2530-5}}</ref>

===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. [[Biology:Human leukocyte antigen|HLA]] class I, class II, and class III genes are associated with SLE, but only classes I and II contribute independently to increased [[Risk|risk]] of SLE.<ref name="pmid19255932">{{cite journal |vauthors=Martens HA, Nolte IM, van der Steege G, etal |title=An extensive screen of the HLA region reveals an independent association of HLA class I and class II with susceptibility for systemic lupus erythematosus |journal=Scand. J. Rheumatol. |volume= 38|issue= 4|pages=256–62 |date=March 2009 |pmid=19255932 |doi=10.1080/03009740802552469 |url=https://semanticscholar.org/paper/252fe8c772d252d5e1d0d6c0c8d2b0f345d59124 }}</ref> Other genes which contain risk variants for SLE are ''[[Biology:IRF5|IRF5]]'', ''[[Biology:PTPN22|PTPN22]]'', ''[[Biology:STAT4|STAT4]]'',<ref name="pmid19225526">{{cite journal |vauthors=Yang W, Ng P, Zhao M, etal |title=Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese |journal=Genes Immun. |volume= 10|issue= 3|pages= 219–26|date=February 2009 |pmid=19225526 |doi=10.1038/gene.2009.1 }}</ref> ''CDKN1A'',<ref name="pmid19262578">{{cite journal |vauthors=Kim K, Sung YK, Kang CP, Choi CB, Kang C, Bae SC |title=A regulatory SNP at position -899 in CDKN1A is associated with systemic lupus erythematosus and lupus nephritis |journal=Genes Immun. |volume= 10|issue= 5|pages= 482–6|date=March 2009 |pmid=19262578 |doi=10.1038/gene.2009.5 }}</ref> ''ITGAM'', ''BLK'',<ref name="pmid19225526"/> ''TNFSF4'' and ''[[Biology:Bank1|BANK1]]''.<ref>{{cite journal |vauthors=Rhodes B, Vyse TJ |title=The genetics of SLE: an update in the light of genome-wide association studies |journal=Rheumatology (Oxford) |volume=47 |issue=11 |pages=1603–11 |date=November 2008 |pmid=18611920 |doi=10.1093/rheumatology/ken247}}</ref> Some of the susceptibility genes may be population specific.<ref name="pmid19225526"/> Genetic studies of the rates of disease in families supports the genetic basis of this disease with a [[Philosophy:Heritability|heritability]] of >66%.<ref name=":2">{{Cite journal|last=Moser|first=K. L.|last2=Kelly|first2=J. A.|last3=Lessard|first3=C. J.|last4=Harley|first4=J. B.|date=2009-07-01|title=Recent insights into the genetic basis of systemic lupus erythematosus|journal=Genes and Immunity|volume=10|issue=5|pages=373–379|doi=10.1038/gene.2009.39|issn=1476-5470|pmc=3144759|pmid=19440199}}</ref> 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% [[Biology:Concordance (genetics)|concordance]] in shared inheritance.<ref name=":2" />

Since SLE is associated with many genetic regions, it is likely an [[Biology:Oligogenic inheritance|oligogenic]] trait, meaning that there are several genes that control susceptibility to the disease.<ref name=":1">{{Cite journal|last=Kelly|first=J. A.|last2=Moser|first2=K. L.|last3=Harley|first3=J. B.|date=2002-10-01|title=The genetics of systemic lupus erythematosus: putting the pieces together|journal=Genes and Immunity|volume=3 Suppl 1|pages=S71–85|doi=10.1038/sj.gene.6363885|issn=1466-4879|pmid=12215907}}</ref>

SLE is regarded as a prototype disease due to the significant overlap in its symptoms with other autoimmune diseases.<ref name=":0">{{Cite journal|last=Prokunina|first=Ludmila|last2=Alarcon-Riquelme|first2=Marta|date=2004-04-01|title=The genetic basis of systemic lupus erythematosus—knowledge of today and thoughts for tomorrow|journal=Human Molecular Genetics|volume=13 Spec No 1|issue=90001|pages=R143–148|doi=10.1093/hmg/ddh076|issn=0964-6906|pmid=14764622}}</ref>

===Drug reactions===
[[Medicine:Drug-induced lupus erythematosus|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 [[Chemistry:Procainamide|procainamide]], [[Chemistry:Isoniazid|isoniazid]], [[Chemistry:Hydralazine|hydralazine]], [[Chemistry:Quinidine|quinidine]], and [[Chemistry:Phenytoin|phenytoin]].<ref>{{cite web |author1=Robert L. Rubin, Ph.D. |title=Drug-Induced Lupus Erythematosus |url=http://www.lupus.org/education/brochures/drug.html |archive-url=https://web.archive.org/web/20061013065604/http://www.lupus.org/education/brochures/drug.html |url-status=dead |website=Lupus Foundation of America |publisher=Lupus Foundation of America |accessdate=20 June 2018 |archivedate=2006-10-13 |location=(non-archive version no longer available)}}</ref><ref name="rahman"/>

===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.<ref>{{cite journal | author = Millard LG | year = 1979 | title = Abnormal Laboratory Test Results and Their Relationship to Prognosis in Discoid Lupus Erythematosus. A Long-term Follow-up Study of 92 Patients | url = | journal = Archives of Dermatology | volume = 115 | issue = 9| pages = 1055–058 | doi=10.1001/archderm.1979.04010090005011}}</ref>

==Pathophysiology==
SLE is triggered by environmental factors that are unknown. In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. These antibody attacks are the immediate cause of SLE.<ref name="rahman">{{cite journal|author1=Anisur Rahman|author2=David A. Isenberg|title=Review Article: Systemic Lupus Erythematosus|journal=N Engl J Med|volume=358|issue=9|pages=929–939|date=February 28, 2008|pmid=18305268|doi=10.1056/NEJMra071297|citeseerx=10.1.1.1008.5428}}</ref><ref>{{cite journal|author=Mary K. Crow|title=Collaboration, Genetic Associations, and Lupus Erythematosus|journal=N Engl J Med|volume=358|issue=9|pages=956–961|date=February 28, 2008|pmid=18204099|doi=10.1056/NEJMe0800096}}</ref><ref>{{cite journal|author1=Geoffrey Hom|author2=Robert R. Graham|author3=Barmak Modrek|title=Association of Systemic Lupus Erythematosus with C8orf13–BLK and ITGAM–ITGAX|journal=N Engl J Med|volume=358|issue=9|pages=900–9|date=February 28, 2008|pmid=18204098|doi=10.1056/NEJMoa0707865|display-authors=0|url=https://semanticscholar.org/paper/4decf9b11b26aeedf87ad0206f6d63a632e9002c}}</ref>

SLE is a chronic [[Medicine:Inflammation|inflammatory]] disease believed to be a type III hypersensitivity response with potential type II involvement.<ref>{{cite web |url=http://pathmicro.med.sc.edu/ghaffar/hyper00.htm |title=University of South Carolina School of Medicine lecture notes, Immunology, Hypersensitivity reactions. General discussion of hypersensitivity, not specific to SLE |publisher=Pathmicro.med.sc.edu |date=2010-07-07 |accessdate=2011-08-06 |url-status=live |archiveurl=https://web.archive.org/web/20110803082424/http://pathmicro.med.sc.edu/ghaffar/hyper00.htm |archivedate=2011-08-03 }}</ref> Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high [[Biology:Titer|titer]]s of anti-cardiolipin antibodies, or a consequence of therapy.<ref>{{cite journal | pmid = 14711150 | volume=2 | issue=6 |date=December 2003 | pages=674–6 |vauthors=Scheinfeld NS, DiCostanzo DD, Cohen SR | title = Reticulate and stellate acral pigmentation associated with systemic lupus erythematosus and high titers of circulating anticardiolipin antibodies: a possible association with acral microlivedo | journal = Journal of Drugs in Dermatology}}</ref>

People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased [[Biology:CD27|CD27]]+/[[Biology:Immunoglobulin D|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), interleukin 6, interleukin 17, interleukin 18, type I interferons, and [[Biology:Tumor necrosis factor alpha|tumor necrosis factor α]] (TNFα) are involved in the inflammatory process and are potential therapeutic targets.<ref name=Lancet2014/><ref name="cruzlancet"/><ref name="pmid19262576">{{cite journal |vauthors=Kanta H, Mohan C |title=Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral amplification by innate immunity and end-organ inflammation |journal=Genes Immun. |volume= 10|issue= 5|pages= 390–6|date=March 2009 |pmid=19262576 |doi=10.1038/gene.2009.6}}</ref>

In the [[Biology:Complement system|complement system]] low C3 levels are associated with systemic lupus erythematosus<ref>{{cite web|url=https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=complement_c3_blood|title=Complement C3 (Blood)—Health Encyclopedia—University of Rochester Medical Center|website=www.urmc.rochester.edu|url-status=live|archiveurl=https://web.archive.org/web/20160924171124/https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=complement_c3_blood|archivedate=2016-09-24}}</ref>

===Cell death signaling===
*Apoptosis is increased in [[Biology:Monocyte|monocyte]]s and [[Biology:Keratinocyte|keratinocyte]]s
*[[Biology:Gene expression|Expression]] of Fas by [[Biology:B cell|B cell]]s and [[Biology:T cell|T cell]]s is increased
*There are correlations between the apoptotic rates of lymphocytes and disease activity.
*Necrosis is increased in T lymphocytes.

[[Biology:Tingible body macrophage|Tingible body macrophage]]s (TBMs)&nbsp;– large [[Biology:Phagocyte|phagocytic cells]] in the germinal centers of secondary [[Biology:Lymph node|lymph node]]s&nbsp;– express [[Biology:CD68|CD68]] protein. These cells normally engulf B cells that have undergone apoptosis after [[Biology:Somatic hypermutation|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. [[Biology:Dendritic cell|Dendritic cell]]s 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-specificity through [[Biology:Somatic hypermutation|somatic hypermutation]].<ref>{{cite book |vauthors=Gaipl US, Kuhn A, Sheriff A, et al |title=Clearance of apoptotic cells in human SLE |journal=Curr. Dir. Autoimmun. |volume=9 |pages=173–87 |year=2006 |pmid=16394661 |doi=10.1159/000090781 |series=Current Directions in Autoimmunity |isbn=978-3-8055-8036-6 }}</ref> Necrosis, a pro-inflammatory form of cell death, is increased in T lymphocytes, due to mitochondrial dysfunction, oxidative stress, and depletion of ATP.<ref>{{cite journal |title=Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus.|author1=Gergely P Jr |author2=Grossman C |author3=Niland B |author4=Puskas F |author5=Neupane H |author6=Allam F |author7=Banki K |author8=Phillips PE |author9=Perl A. |pmid=11817589 |doi=10.1002/1529-0131(200201)46:1<175::AID-ART10015>3.0.CO;2-H |volume=46 |issue=1 |pmc=4020417 |date=January 2002 |journal=Arthritis Rheum. |pages=175–90}}</ref>

===Clearance deficiency===
[[File:Picture1 englisch.jpg|thumb|Clearance deficiency]] 
Impaired clearance of dying cells is a potential pathway for the development of this systemic [[Medicine:Autoimmune disease|autoimmune disease]]. This includes deficient phagocytic activity and scant serum components in addition to increased [[Biology:Apoptosis|apoptosis]].

<!--The Lancet uses the terms “eat-me” and “find-me” to describe the mechanisms of apoptotic cells. Please do not change this unless you are a medical scientist who understands it better and knows how to explain it better than the authors of this review article.-->
SLE is associated with defects in [[Biology:Apoptosis|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 development of antinuclear antibodies.<ref name=Lancet2014/>

Monocytes isolated from [[Medicine:Whole blood|whole blood]] of people with SLE show reduced expression of [[Biology:CD44|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 [[Biology:Complement system|complement]] factors, [[Chemistry:C-reactive protein|CRP]], and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient.

Recent research has found an association between certain people with lupus (especially those with [[Medicine:Lupus nephritis|lupus nephritis]]) and an impairment in degrading [[Biology:Neutrophil extracellular traps|neutrophil extracellular traps]] (NETs). These were due to [[Biology:Deoxyribonuclease I|DNAse1]] inhibiting factors, or NET protecting factors in people's serum, rather than abnormalities in the DNAse1 itself.<ref>{{cite journal |vauthors=Hakkim A, Fürnrohr BG, Amann K, etal |title=Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=107 |issue=21 |pages=9813–8 |date=May 2010 |pmid=20439745 |pmc=2906830 |doi=10.1073/pnas.0909927107 |bibcode=2010PNAS..107.9813H }}</ref> DNAse1 mutations in lupus have so far only been found in some Japanese cohorts.<ref>{{cite journal |vauthors=Yasutomo K, Horiuchi T, Kagami S, etal |title=Mutation of DNASE1 in people with systemic lupus erythematosus |journal=Nat. Genet. |volume=28 |issue= 4 |pages= 313–4 |year= 2001 |pmid= 11479590 |doi= 10.1038/91070 }}</ref>

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 [[Biology:Necrosis|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 maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules.
[[Medicine:Autoimmunity|Autoimmunity]] possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and [[Biology:T cell|T cell]] tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; [[Medicine:Inflammation|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).<ref>{{cite journal |vauthors=Gaipl US, Munoz LE, Grossmayer G, et al |title=Clearance deficiency and systemic lupus erythematosus (SLE) |journal=J. Autoimmun. |volume=28 |issue=2–3 |pages=114–21 |year=2007 |pmid=17368845 |doi=10.1016/j.jaut.2007.02.005 }}</ref>

===Germinal centers===
[[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 lack of TBM and many uningested apoptotic cells decorating the surfaces of spindle-shaped cell, 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, buildup of apoptotic [[Physics:Debris|debris]] can be observed in GC because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to [[Biology:Bone marrow|bone marrow]]-derived DC, neither take it up nor present it via [[Biology:Major histocompatibility complex|MHC]] molecules.

Autoreactive B cells can accidentally emerge during [[Biology:Somatic hypermutation|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 [[Medicine:Autoimmune disease|autoimmune disease]] may be the consequence.

===Anti-nRNP autoimmunity===
Anti-nRNP autoantibodies to nRNP A and nRNP C initially targeted restricted, [[Chemistry:Proline|proline]]-rich [[Biology:Sequence motif|motifs]]. Antibody binding subsequently spread to other epitopes. The similarity and [[Biology:Cross-reactivity|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.<ref name="pmid19248110">{{cite journal |vauthors=Poole BD, Schneider RI, Guthridge JM, etal |title=Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus |journal=Arthritis Rheum. |volume=60 |issue=3 |pages=848–859 |date=February 2009 |pmid=19248110 |doi=10.1002/art.24306 |pmc=2653589}}</ref>

===Others===
Elevated expression of [[Biology:HMGB1|HMGB1]] was found in the sera of people and mice with systemic lupus erythematosus, high mobility group box 1 ([[Biology:HMGB1|HMGB1]]) is a [[Biology:Cell nucleus|nuclear]] [[Biology:Protein|protein]] participating in [[Biology:Chromatin|chromatin]] architecture and transcriptional regulation. Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic [[Medicine:Inflammation|inflammatory]] and autoimmune diseases due to its inflammatory and immune stimulating properties.<ref name="pmid19247800">{{cite journal |vauthors=Pan HF, Wu GC, Li WP, Li XP, Ye DQ |title=High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus |journal=Mol. Biol. Rep. |volume= 37|issue= 3|pages= 1191–5|date=February 2009 |pmid=19247800 |doi=10.1007/s11033-009-9485-7 }}</ref>

==Diagnosis==
[[Image:Vacuolar interface dermatitis - high mag.jpg|thumb|[[Micrograph|Micrograph]] showing vacuolar interface dermatitis, as may be seen in SLE. H&E stain.]]
[[File:Lupus band test.jpg|thumb|Micrograph of a [[Biology:Histology|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===
[[Biology:Antinuclear antibody|Antinuclear antibody]] (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of [[Biology:Serology|serologic]] testing for SLE. If ANA is negative the disease can be ruled out.<ref>{{cite journal |last1=Aringer |first1=M |last2=Costenbader |first2=K |last3=Daikh |first3=D |last4=Brinks |first4=R |last5=Mosca |first5=M |last6=Ramsey-Goldman |first6=R |last7=Smolen |first7=JS |last8=Wofsy |first8=D |last9=Boumpas |first9=DT |last10=Kamen |first10=DL |last11=Jayne |first11=D |last12=Cervera |first12=R |last13=Costedoat-Chalumeau |first13=N |last14=Diamond |first14=B |last15=Gladman |first15=DD |last16=Hahn |first16=B |last17=Hiepe |first17=F |last18=Jacobsen |first18=S |last19=Khanna |first19=D |last20=Lerstrøm |first20=K |last21=Massarotti |first21=E |last22=McCune |first22=J |last23=Ruiz-Irastorza |first23=G |last24=Sanchez-Guerrero |first24=J |last25=Schneider |first25=M |last26=Urowitz |first26=M |last27=Bertsias |first27=G |last28=Hoyer |first28=BF |last29=Leuchten |first29=N |last30=Tani |first30=C |last31=Tedeschi |first31=SK |last32=Touma |first32=Z |last33=Schmajuk |first33=G |last34=Anic |first34=B |last35=Assan |first35=F |last36=Chan |first36=TM |last37=Clarke |first37=AE |last38=Crow |first38=MK |last39=Czirják |first39=L |last40=Doria |first40=A |last41=Graninger |first41=W |last42=Halda-Kiss |first42=B |last43=Hasni |first43=S |last44=Izmirly |first44=PM |last45=Jung |first45=M |last46=Kumánovics |first46=G |last47=Mariette |first47=X |last48=Padjen |first48=I |last49=Pego-Reigosa |first49=JM |last50=Romero-Diaz |first50=J |last51=Rúa-Figueroa Fernández |first51=Í |last52=Seror |first52=R |last53=Stummvoll |first53=GH |last54=Tanaka |first54=Y |last55=Tektonidou |first55=MG |last56=Vasconcelos |first56=C |last57=Vital |first57=EM |last58=Wallace |first58=DJ |last59=Yavuz |first59=S |last60=Meroni |first60=PL |last61=Fritzler |first61=MJ |last62=Naden |first62=R |last63=Dörner |first63=T |last64=Johnson |first64=SR |title=2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. |journal=Arthritis & Rheumatology |date=September 2019 |volume=71 |issue=9 |pages=1400–1412 |doi=10.1002/art.40930 |pmid=31385462|pmc=6827566 }}</ref>

Several techniques are used to detect ANAs. The most widely used is indirect [[Biology:Immunofluorescence|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 the people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called lupus band test) is an evidence of systemic lupus erythematosus.<ref>Ther Clin Risk Manag. 2011; 7: 27–32. The lupus band test in systemic lupus erythematosus patients. Adam Reich, Katarzyna Marcinow, and Rafal Bialynicki-Birula</ref>

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 [[Biology:LSm|anti-Smith]] and anti-double stranded [[Biology:DNA|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.<ref name="rahman"/> The anti-dsDNA antibody [[Biology:Titer|titer]]s also tend to reflect disease activity, although not in all cases.<ref name="rahman"/> Other ANA that may occur in people with SLE are [[Biology:U1 spliceosomal RNA|anti-U1 RNP]] (which also appears in systemic sclerosis and [[Medicine:Mixed connective tissue disease|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.<ref name="pmid14671725">{{cite journal |vauthors=Buyon JP, Clancy RM |title=Maternal autoantibodies and congenital heart block: mediators, markers, and therapeutic approach |journal=Semin. Arthritis Rheum. |volume=33 |issue=3 |pages=140–54 |date=December 2003 |pmid=14671725 |doi= 10.1016/j.semarthrit.2003.09.002}}</ref>

Other tests routinely performed in suspected SLE are [[Biology:Complement system|complement system]] levels (low levels suggest consumption by the immune system), [[Physics:Electrolyte|electrolyte]]s and kidney function (disturbed if the kidney is involved), liver enzymes, and [[Medicine:Complete blood count|complete blood count]].

The [[Medicine:Lupus erythematosus|lupus erythematosus]] (LE) cell test was commonly used for diagnosis, but it is no longer used because the [[Biology:LE cell|LE cell]]s 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.<ref>[https://www.nlm.nih.gov/medlineplus/ency/article/003635.htm NIM encyclopedic article on the LE cell test] {{webarchive |url=https://web.archive.org/web/20061006161855/https://www.nlm.nih.gov/medlineplus/ency/article/003635.htm |date=October 6, 2006 }}</ref>

===Diagnostic criteria===
Some physicians make a diagnosis on the basis of the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in [[Randomized controlled trial|randomized controlled trial]]s which require higher confidence levels, so many people with SLE may not pass the full criteria.

====Criteria====
The American College of Rheumatology (ACR) established eleven criteria in 1982,<ref>{{cite web |url=http://www.rheumatology.org/publications/classification/index.asp?aud=mem |title=Article on the classification of rheumatic diseases |publisher=Rheumatology.org |date=2011-06-08 |accessdate=2011-08-06 |url-status=live |archiveurl=https://web.archive.org/web/20110718192030/http://www.rheumatology.org/publications/classification/index.asp?aud=mem |archivedate=2011-07-18 }}</ref> which were revised in 1997<ref>{{cite web |url=http://www.rheumatology.org/publications/classification/SLE/1982SLEupdate.asp?aud=mem |title=Revision of Rheumatology.org's diagnostic criteria |publisher=Rheumatology.org |date=2011-06-08 |accessdate=2011-08-06 |url-status=live |archiveurl=https://web.archive.org/web/20110718192053/http://www.rheumatology.org/publications/classification/SLE/1982SLEupdate.asp?aud=mem |archivedate=2011-07-18 }}</ref> 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.

# Malar rash (rash on cheeks); [[Sensitivity and specificity|sensitivity]] = 57%; [[Sensitivity and specificity|specificity]] = 96%.<ref name="pmid3060613"/>
# Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%.<ref name="pmid3060613"/>
# Serositis: [[Medicine:Pleurisy|Pleurisy]] (inflammation of the membrane around the lungs) or [[Medicine:Pericarditis|pericarditis]] (inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific).<ref name="pmid3060613"/>
# Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%; specificity = 96%.<ref name="pmid3060613"/>
# [[Medicine:Arthritis|Arthritis]]: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%.<ref name="pmid3060613"/>
# Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%.<ref name="pmid3060613"/>
# Blood—hematologic disorder—hemolytic anemia (low [[Biology:Red blood cell|red blood cell]] count), [[Medicine:Leukopenia|leukopenia]] (white blood cell count<4000/µl), lymphopenia (<1500/µl), or [[Medicine:Thrombocytopenia|low platelet count]] (<100000/µl) in the absence of offending drug; sensitivity = 59%; specificity = 89%.<ref name="pmid3060613"/> Hypocomplementemia is also seen, due to either consumption of C3<ref name="pmid6600582">{{cite journal|last=Weinstein|first=A|author2=Bordwell, B |author3=Stone, B |author4=Tibbetts, C |author5= Rothfield, NF |title=Antibodies to native DNA and serum complement (C3) levels. Application to diagnosis and classification of systemic lupus erythematosus.|journal=The American Journal of Medicine|date=February 1983|volume=74|issue=2|pages=206–16|pmid=6600582|doi=10.1016/0002-9343(83)90613-7}}</ref> and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE.
# Renal disorder: More than 0.5&nbsp;g per day protein in urine or cellular casts seen in urine under a microscope; sensitivity = 51%; specificity = 94%.<ref name="pmid3060613"/>
# [[Biology:Antinuclear antibody|Antinuclear antibody]] test positive; sensitivity = 99%; specificity = 49%.<ref name="pmid3060613"/>
# Immunologic disorder: Positive [[Biology:LSm#History|anti-Smith]], anti-ds DNA, [[Medicine:Antiphospholipid syndrome|antiphospholipid antibody]], or false positive [[Biology:Serology|serological]] test for [[Medicine:Syphilis|syphilis]]; sensitivity = 85%; specificity = 93%.<ref name="pmid3060613"/> Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons).<ref>{{cite web |url=http://patients.uptodate.com/topic.asp?file=dx_rheum/18305 |title=UpToDate Patient information article on DNA antibodies |publisher=Patients.uptodate.com |accessdate=2011-08-06 |url-status=live |archiveurl=https://web.archive.org/web/20071011145146/http://patients.uptodate.com/topic.asp?file=dx_rheum%2F18305 |archivedate=2007-10-11 }}</ref>
# Neurologic disorder: [[Medicine:Seizure|Seizure]]s or [[Medicine:Psychosis|psychosis]]; sensitivity = 20%; specificity = 98%.<ref name="pmid3060613"/>

Other than the ACR criteria, people with lupus may also have:<ref name="Common Symptoms of Lupus : lupus.org">{{cite web|title=Common Symptoms of Lupus|url=http://www.lupus.org/webmodules/webarticlesnet/templates/new_learndiagnosing.aspx?articleid=2241&zoneid=524|publisher=Lupus Foundation of America|accessdate=7 June 2013|url-status=dead|archiveurl=https://web.archive.org/web/20130419103517/http://www.lupus.org/webmodules/webarticlesnet/templates/new_learndiagnosing.aspx?articleid=2241&zoneid=524|archivedate=2013-04-19}}</ref>
* fever (over 100&nbsp;°F/ 37.7&nbsp;°C)
* extreme fatigue
* hair loss
* fingers turning white or blue when cold (Raynaud's phenomenon)

====Criteria for individual diagnosis====
Some people, especially those with [[Medicine:Antiphospholipid syndrome|antiphospholipid syndrome]], may have SLE without four of the above criteria, and also SLE may present with features other than those listed in the criteria.<ref name="pmid12892393">{{cite journal |vauthors=Asherson RA, Cervera R, de Groot PG, etal |title=Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines |journal=Lupus |volume=12 |issue=7 |pages=530–4 |year=2003 |pmid=12892393 |url=http://openurl.ingenta.com/content/nlm?genre=article&issn=0961-2033&volume=12&issue=7&spage=530&aulast=Asherson |doi=10.1191/0961203303lu394oa}}</ref><ref name="pmid15608315">{{cite journal |vauthors=Sangle S, D'Cruz DP, Hughes GR |title=Livedo reticularis and pregnancy morbidity in patients negative for antiphospholipid antibodies |journal=Ann. Rheum. Dis. |volume=64 |issue=1 |pages=147–8 |year=2005 |pmid=15608315 |doi=10.1136/ard.2004.020743 |pmc=1755191}}</ref><ref name="pmid14644846">{{cite journal |vauthors=Hughes GR, Khamashta MA |title=Seronegative antiphospholipid syndrome |journal=Ann. Rheum. Dis. |volume=62 |issue=12 |page=1127 |year=2003 |pmid=14644846| doi = 10.1136/ard.2003.006163 |pmc=1754381}}</ref>

[[Recursive partitioning]] has been used to identify more parsimonious criteria.<ref name="pmid3060613">{{cite journal |vauthors=Edworthy SM, Zatarain E, McShane DJ, Bloch DA |title=Analysis of the 1982 ARA lupus criteria data set by recursive partitioning methodology: new insights into the relative merit of individual criteria |journal=J. Rheumatol. |volume=15 |issue=10 |pages=1493–8 |year=1988 |pmid=3060613 |doi=}}</ref> This analysis presented two diagnostic classification trees:

# Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash. It has sensitivity = 92% and specificity = 92%.
# Full classification tree: Uses 6 criteria. It has sensitivity = 97% and specificity = 95%.

Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital "alternative" criteria in 1998.<ref name="pmid9631744">{{cite journal |author=Hughes GR |title=Is it lupus? The St. Thomas' Hospital "alternative" criteria |journal=Clin. Exp. Rheumatol. |volume=16 |issue=3 |pages=250–2 |year=1998 |pmid=9631744 |doi= }}</ref>

==Treatment==
The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.

Treatment can include [[Biology:Corticosteroid|corticosteroid]]s and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require intermittent cytotoxic drugs. These drugs include [[Chemistry:Cyclophosphamide|cyclophosphamide]] and mycophenolate. Cyclophosphamide increases the risk of developing infections, pancreas problems, high blood sugar, and high blood pressure.<ref>{{Cite journal|last=Fernandes Moça Trevisani|first=Virginia|last2=Castro|first2=Aldemar A|last3=Ferreira Neves Neto|first3=João|last4=Atallah|first4=Álvaro N|date=2013-02-28|title=Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus|journal=Cochrane Database of Systematic Reviews|issue=2|pages=CD002265|doi=10.1002/14651858.cd002265.pub3|pmid=23450535|pmc=6823222|issn=1465-1858}}</ref>

[[Chemistry:Hydroxychloroquine|Hydroxychloroquine]] was approved by the [[Organization:Food and Drug Administration|FDA]] for lupus in 1955.<ref name=Vasudevan/> Some drugs approved for other diseases are used for SLE 'off-label'. In November 2010, an FDA advisory panel recommended approving [[Chemistry:Belimumab|belimumab]] (Benlysta) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.<ref name="Benlysta">{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm246489.htm |title=FDA approves first new lupus drug in 56 years |accessdate=6 May 2011 |url-status=live |archiveurl=https://web.archive.org/web/20110503191041/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm246489.htm |archivedate=3 May 2011 }}</ref><ref name="Vincent FB, Morand EF and Mackay F 2012 293–303">{{cite journal|url=http://www.nature.com/icb/journal/vaop/ncurrent/abs/icb2011111a.html |vauthors=Vincent FB, Morand EF, Mackay F |title=BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus |journal=Immunology and Cell Biology |year=2012 |doi=10.1038/icb.2011.111 |accessdate=10 January 2012|volume=90|issue=3|pages=293–303|pmid=22231653}}</ref>

===Medications===
Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, [[Chemistry:Nonsteroidal anti-inflammatory drug|nonsteroidal anti-inflammatory drug]]s and [[Medicine:Malaria|antimalarials]] may be used. Medications such as [[Chemistry:Prednisone|prednisone]], [[Chemistry:Mycophenolic acid|mycophenolic acid]] and [[Chemistry:Tacrolimus|tacrolimus]] have been used in the past.

====Disease-modifying antirheumatic drugs====
Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce the incidence of flares, the progress of the disease, and the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as [[Chemistry:Hydroxychloroquine|hydroxychloroquine]] and immunosuppressants (e.g. [[Chemistry:Methotrexate|methotrexate]] and [[Chemistry:Azathioprine|azathioprine]]). Hydroxychloroquine is an FDA-approved antimalarial used for constitutional, cutaneous, and articular manifestations. Hydroxychloroquine has relatively few side effects, and there is evidence that it improves survival among people who have SLE.<ref name="Vasudevan">{{cite journal |vauthors=Vasudevan AR, Ginzler EM |title=Established and novel treatments for lupus |journal=The Journal of Musculoskeletal Medicine |volume=26 |issue=8 |date=August 4, 2009 |url=http://www.musculoskeletalnetwork.com/lupus/article/1145622/1434518 }}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref>
[[Chemistry:Cyclophosphamide|Cyclophosphamide]] is used for severe [[Medicine:Glomerulonephritis|glomerulonephritis]] or other organ-damaging complications. [[Chemistry:Mycophenolic acid|Mycophenolic acid]] is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women.<ref>{{cite journal|title=FDA Alert: Mycophenolate Mofetil (marketed as CellCept) and Mycophenolic Acid (marketed as Myfortic)|date=May 16, 2008|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124776.htm|url-status=live|archiveurl=https://web.archive.org/web/20100803153442/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124776.htm|archivedate=August 3, 2010}}</ref>

====Immunosuppressive drugs====
In more severe cases, medications that modulate the immune system (primarily corticosteroids and [[Chemistry:Immunosuppressive drug|immunosuppressants]]) are used to control the disease and prevent recurrence of symptoms (known as flares). Depending on the dosage, people who require steroids may develop [[Medicine:Cushing's syndrome|Cushing's syndrome]], symptoms of which may include obesity, puffy round face, [[Medicine:Diabetes mellitus|diabetes mellitus]], increased appetite, difficulty sleeping and [[Medicine:Osteoporosis|osteoporosis]]. These may subside if and when the large initial dosage is reduced, but long-term use of even low doses can cause elevated [[Physics:Blood pressure|blood pressure]] and cataracts.

Numerous new immunosuppressive drugs are being actively tested for SLE. Rather than suppressing the immune system nonspecifically, as corticosteroids do, they target the responses of individual [types of] immune cells. Some of these drugs are already FDA-approved for treatment of [[Medicine:Rheumatoid arthritis|rheumatoid arthritis]], however due to high-toxicity, its use is limited.<ref name=Vasudevan/><ref>{{Cite journal|last=Suarez-Almazor|first=Maria E|last2=Belseck|first2=Elaine|last3=Shea|first3=Beverley|last4=Tugwell|first4=Peter|last5=Wells|first5=George A|date=2000-10-23|title=Cyclophosphamide for treating rheumatoid arthritis|journal=Cochrane Database of Systematic Reviews|doi=10.1002/14651858.cd001157|issn=1465-1858}}</ref>

====Analgesia====
Since a large percentage of people with SLE have varying amounts of [[Medicine:Chronic pain|chronic pain]], stronger prescription analgesics (painkillers) may be used if over-the-counter drugs (mainly [[Chemistry:Nonsteroidal anti-inflammatory drug|nonsteroidal anti-inflammatory drug]]s) do not provide effective relief. Potent NSAIDs such as indomethacin and [[Chemistry:Diclofenac|diclofenac]] are relatively contraindicated for people with SLE because they increase the risk of kidney failure and heart failure.<ref name=Vasudevan/>

Pain is typically treated with opioids, varying in potency based on the severity of symptoms. When opioids are used for prolonged periods, drug tolerance, chemical dependency, and addiction may occur. Opiate addiction is not typically a concern since the condition is not likely to ever completely disappear. Thus, lifelong treatment with opioids is fairly common for chronic pain symptoms, accompanied by periodic titration that is typical of any long-term opioid regimen.

====Intravenous immunoglobulins (IVIGs)====
Intravenous immunoglobulins may be used to control SLE with organ involvement, or [[Medicine:Vasculitis|vasculitis]]. It is believed that they reduce [[Biology:Antibody|antibody]] production or promote the clearance of [[Biology:Immune complex|immune complex]]es from the body, even though their [[Chemistry:Mechanism of action|mechanism of action]] is not well understood.<ref>{{cite web |url=http://www.niams.nih.gov/Health_Info/Lupus/default.asp |title=Handout on Health: Systemic Lupus Erythematosus, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, U.S. Department of Health and Human Services |accessdate=2010-10-13 |url-status=live |archiveurl=https://web.archive.org/web/20101204095742/http://www.niams.nih.gov/Health_Info/Lupus/default.asp |archivedate=2010-12-04 }}</ref> Unlike immunosuppressives and corticosteroids, IVIGs do not suppress the [[Biology:Immune system|immune system]], so there is less risk of serious [[Medicine:Infection|infection]]s with these drugs.<ref>{{cite web |url=http://theodora.com/lupus_central_station/intravenous_immunoglobulins_ivigs.html |title=Intravenous Immunoglobulins (IVIGs) in Lupus Central Station, sourced from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, U.S. Department of Health and Human Services |accessdate=2010-10-13 |url-status=live |archiveurl=https://web.archive.org/web/20111020213817/http://theodora.com/lupus_central_station/intravenous_immunoglobulins_ivigs.html |archivedate=2011-10-20 }}</ref>

===Lifestyle changes===
Avoiding sunlight in SLE is critical, since sunlight is known to exacerbate skin manifestations of the disease. Avoiding activities which induce fatigue is also important, since those with SLE fatigue easily and it can be debilitating. These two problems can lead to people becoming housebound for long periods of time. Drugs unrelated to SLE should be prescribed only when known not to exacerbate the disease. Occupational exposure to [[Chemistry:Silica|silica]], [[Biology:Pesticide|pesticide]]s, and [[Chemistry:Mercury (element)|mercury]] can also worsen the disease.<ref name="cruzlancet">{{cite journal |vauthors=D'Cruz DP, Khamashta MA, Hughes GR | title = Systemic lupus erythematosus | journal = Lancet | volume = 369 | issue = 9561 | pages = 587–96 |date=February 2007 | pmid = 17307106 | doi = 10.1016/S0140-6736(07)60279-7 | citeseerx = 10.1.1.1008.5428 }}</ref>

===Kidney transplantation===
Kidney transplants are the treatment of choice for end-stage kidney disease, which is one of the complications of [[Medicine:Lupus nephritis|lupus nephritis]], but the recurrence of the full disease is common in up to 30% of people.<ref name="pmid19247694">{{cite journal |vauthors=Cochat P, Fargue S, Mestrallet G, etal |title=Disease recurrence in paediatric renal transplantation |journal=Pediatr. Nephrol. |volume= 24|issue= 11|pages= 2097–108|date=February 2009 |pmid=19247694 |doi=10.1007/s00467-009-1137-6 |pmc=2753770}}</ref>

===Antiphospholipid syndrome===

Approximately 20% of people with SLE have clinically significant levels of antiphospholipid antibodies, which are associated with [[Medicine:Antiphospholipid syndrome|antiphospholipid syndrome]].<ref>{{cite journal | last1=Ünlü | first1=O | last2=Zuily | first2=S | last3=Erkan | first3=D | title=The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus | journal=European Journal of Rheumatology | volume=3 | issue=2 | pages=75–84 | year=2016 | pmid=27708976 | pmc=5042235 | doi=10.5152/eurjrheum.2015.0085 }}</ref> Antiphospholipid syndrome is also related to the onset of neural lupus symptoms in the brain. In this form of the disease the cause is very different from lupus: thromboses (blood clots or "sticky blood") form in blood vessels, which prove to be fatal if they move within the blood stream.<ref name="pmid12892393"/> If the thromboses migrate to the brain, they can potentially cause a [[Medicine:Stroke|stroke]] by blocking the blood supply to the brain.

If this disorder is suspected in people, brain scans are usually required for early detection. These scans can show localized areas of the brain where blood supply has not been adequate. The treatment plan for these people requires anticoagulation. Often, low-dose [[Chemistry:Aspirin|aspirin]] is prescribed for this purpose, although for cases involving thrombosis anticoagulants such as [[Chemistry:Warfarin|warfarin]] are used.<ref>{{cite journal |vauthors=Danchenko N, Satia JA, Anthony MS |title=Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden |journal=Lupus |volume=15 |issue=5 |pages=308–18 |year=2006 |pmid=16761508 |url=http://openurl.ingenta.com/content/nlm?genre=article&issn=0961-2033&volume=15&issue=5&spage=308&aulast=Danchenko |doi=10.1191/0961203306lu2305xx}}</ref>

===Management of pregnancy===
While most infants born to mothers who have SLE are healthy, pregnant mothers with SLE should remain under medical care until delivery. Neonatal lupus is rare, but identification of mothers at highest risk for complications allows for prompt treatment before or after birth. In addition, SLE can flare up during pregnancy, and proper treatment can maintain the health of the mother longer. Women pregnant and known to have anti-Ro (SSA) or anti-La antibodies (SSB) often have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.<ref name=niams>{{cite web |url=http://www.niams.nih.gov/Health_Info/Lupus/default.asp |title=Handout on Health: Systemic Lupus Erythematosus |accessdate=2007-11-23 |date=August 2003 |work=The National Institute of Arthritis and Musculoskeletal and Skin Diseases |publisher=National Institutes of Health |url-status=live |archiveurl=https://web.archive.org/web/20071018040714/http://www.niams.nih.gov/Health_Info/Lupus/default.asp |archivedate=2007-10-18 }}</ref>

Contraception and other reliable forms of pregnancy prevention is routinely advised for women with SLE, since getting pregnant during active disease was found to be harmful. [[Medicine:Lupus nephritis|Lupus nephritis]] was the most common manifestation.

==Prognosis==
No cure is available for SLE but there are many treatments for the disease.<ref name=NIH2015/>

In the 1950s, most people diagnosed with SLE lived fewer than five years. Today, over 90% now survive for more than ten years, and many live relatively symptom-free. 80–90% can expect to live a normal lifespan.<ref name="Prognosis and a Hopeful Future">{{cite web|title=Prognosis and a Hopeful Future|url=http://www.lupus.org/webmodules/webarticlesnet/templates/new_learnunderstanding.aspx?articleid=2238&zoneid=523|work=Lupus Foundation of America website|accessdate=14 December 2010|url-status=dead|archiveurl=https://web.archive.org/web/20110320042014/http://www.lupus.org/webmodules/webarticlesnet/templates/new_learnunderstanding.aspx?articleid=2238&zoneid=523|archivedate=20 March 2011}}</ref> Mortality rates are however elevated compared to people without SLE.<ref>{{cite journal |last1=Singh |first1=RR |last2=Yen |first2=EY |title=SLE mortality remains disproportionately high, despite improvements over the last decade. |journal=Lupus |date=September 2018 |volume=27 |issue=10 |pages=1577–1581 |doi=10.1177/0961203318786436 |pmid=30016928|pmc=6082727 }}</ref>

Prognosis is typically worse for men and children than for women; however, if symptoms are present after age 60, the disease tends to run a more benign course. Early mortality, within 5 years, is due to organ failure or overwhelming infections, both of which can be altered by early diagnosis and treatment. The mortality risk is fivefold when compared to the normal population in the late stages, which can be attributed to cardiovascular disease from accelerated atherosclerosis, the leading cause of death for people with SLE.<ref name=Vasudevan/> To reduce the potential for cardiovascular issues, high blood pressure and high cholesterol should be prevented or treated aggressively. Steroids should be used at the lowest dose for the shortest possible period, and other drugs that can reduce symptoms should be used whenever possible.<ref name=Vasudevan/>

==Epidemiology==
The global rates of SLE are approximately 20–70 per 100,000 people. In females, the rate is highest between 45 and 64 years of age. The lowest overall rate exists in Iceland and Japan. The highest rates exist in the US and France. However, there is not sufficient evidence to conclude why SLE is less common in some countries compared to others; it could be the environmental variability in these countries. For example, different countries receive different levels of sunlight, and exposure to UV rays affects dermatological symptoms of SLE. Certain studies hypothesize that a genetic connection exists between race and lupus which affects disease prevalence. If this is true, the racial composition of countries affects disease, and will cause the incidence in a country to change as the racial makeup changes. In order to understand if this is true, countries with largely homogenous and racially stable populations should be studied to better understand incidence.<ref name=Dan2006/> Rates of disease in the developing world are unclear.<ref name=Tif2013/>

The rate of SLE varies between countries, ethnicity, and sex, and changes over time.<ref name=Epi2006>{{cite journal |vauthors=Danchenko N, Satia JA, Anthony MS |title=Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden |journal=Lupus |volume=15 |issue=5 |pages=308–18 |year=2006 |pmid=16761508 |doi= 10.1191/0961203306lu2305xx|url=http://openurl.ingenta.com/content/nlm?genre=article&issn=0961-2033&volume=15&issue=5&spage=308&aulast=Danchenko}}</ref> In the United States, one estimate of the [[Prevalence|rate]] of SLE is 53 per 100,000;<ref name=Epi2006/> another estimate places the total affected population at 322,000 to over 1 million (98 to over 305 per 100,000).<ref name=CDC/> In Northern Europe the rate is about 40 per 100,000 people.<ref name=Rahman2008>{{cite journal |vauthors=Rahman A, Isenberg DA |title=Systemic lupus erythematosus |journal=N. Engl. J. Med. |volume=358 |issue=9 |pages=929–39 |date=February 2008 |pmid=18305268 |doi=10.1056/NEJMra071297 |citeseerx=10.1.1.1008.5428 }}</ref> SLE occurs more frequently and with greater severity among those of non-European descent.<ref name=CDC>{{cite web |url=https://www.cdc.gov/omhd/AMH/factsheets/lupus.htm |title=OMHD&#124;AMH&#124;Factsheets&#124;Lupus |url-status=dead |archiveurl=https://web.archive.org/web/20090111033453/http://www.cdc.gov/omhd/AMH/factsheets/lupus.htm |archivedate=2009-01-11 |access-date=2017-09-15 |df= }}</ref> That rate has been found to be as high as 159 per 100,000 among those of Afro-Caribbean descent.<ref name=Epi2006/> Childhood-onset systemic lupus erythematosus generally presents between the ages of 3 and 15 and is four times more common in girls.<ref>{{cite journal|last1=Borgia|first1=RE|last2=Silverman|first2=ED|title=Childhood-onset systemic lupus erythematosus: an update.|journal=Current Opinion in Rheumatology|date=September 2015|volume=27|issue=5|pages=483–92|pmid=26200474|doi=10.1097/bor.0000000000000208}}</ref>

While the onset and persistence of SLE can show disparities between genders, socioeconomic status also plays a major role. Women with SLE and of lower socioeconomic status have been shown to have higher depression scores, higher body mass index, and more restricted access to medical care than women of higher socioeconomic statuses with the illness. People with SLE had more self-reported anxiety and depression scores if they were from a lower socioeconomic status.<ref>{{cite journal | author = Sule S, Petri M | year = 2006 | title = Socioeconomic Status in Systemic Lupus Erythematosus | url = | journal = Lupus | volume = 15 | issue = 11| pages = 720–23 | doi=10.1177/0961203306070008| pmid = 17153841 }}</ref>

===Ethnicity===
There are assertions that race affects the rate of SLE. However, a 2010 review of studies which correlate race and SLE identified several sources of systematic and methodological error, indicating that the connection between race and SLE may be spurious.<ref name=Pons-Estel>{{cite journal|last1=Pons-Estel|first1=Guillermo J|last2=Alarcon|first2=Graciela S|last3=Scofield|first3=Lacie|last4=Cooper|first4=Glinda S|title=Understanding the Epidemiology and Progression of Systemic Lupus Erythematosus|journal=Seminars in Arthritis and Rheumatism|date=February 2010|volume=39|issue=4|pages=257–68|doi=10.1016/j.semarthrit.2008.10.007|pmid=19136143|pmc=2813992}}</ref> For example, studies show that social support is a modulating factor which buffers against SLE-related damage and maintains physiological functionality.<ref name=Pons-Estel/> Studies have not been conducted to determine whether people of different racial backgrounds receive differing levels of social support.<ref name=Pons-Estel/> If there is a difference, this could act as a confounding variable in studies correlating race and SLE. Another caveat to note when examining studies about SLE is that symptoms are often self-reported. This process introduces additional sources of methodological error. Studies have shown that self-reported data is affected by more than just the patients experience with the disease- social support, the level of helplessness, and abnormal illness-related behaviors also factor into a self-assessment. Additionally, other factors like the degree of social support that a person receives, socioeconomic status, health insurance, and access to care can contribute to an individual's disease progression.<ref name=Pons-Estel/><ref>{{cite journal|last1=Ow|first1=M.Y.|last2=Ho|first2=P.C.|last3=Thumboo|first3=J.|last4=Wee|first4=H.L.|title=Factors associated with health services utilization in patients with systemic lupus erythematosus: a systematic review|journal=Clinical and Experimental Rheumatology|date=Nov–Dec 2010|volume=28|issue=6|pages=892–904|pmid=21122271}}</ref> Racial differences in lupus progression have not been found in studies that control for the socioeconomic status [SES] of participants.<ref name=Pons-Estel/><ref name="ReferenceA">{{cite journal|last1=Yelin|first1=Edward|last2=Yazdany|first2=Jinoos|last3=Tonner|first3=Chris|last4=Criswell|first4=Lindsey A|last5=Katz|first5=Patricia|last6=Schamjuk|first6=Gabriela|title=Interactions between patients, providers, and health systems and technical quality of care|journal=Arthritis Care & Research|date=2014|doi=10.1002/acr.22427|pmid=25132660|volume=67|issue=3|pages=417–424|pmc=4320034}}</ref> Studies that control for the SES of its participants have found that non-white people have more abrupt disease onset compared to white people and that their disease progresses more quickly. Non-white patients often report more hematological, serosal, neurological, and renal symptoms. However, the severity of symptoms and mortality are both similar in white and non-white patients. Studies that report different rates of disease progression in late-stage SLE are most likely reflecting differences in socioeconomic status and the corresponding access to care.<ref name=Pons-Estel/> The people who receive medical care have often accrued less disease-related damage and are less likely to be below the poverty line.<ref name="ReferenceA"/> Additional studies have found that education, marital status, occupation, and income create a social context which contributes to disease progression.<ref name=Pons-Estel/>

===Sex===
SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of about 9 to 1.<ref name= Murphy2013 /><ref name=Epi2006/> The X chromosome carries immunological related genes, which can mutate and contribute to the onset of SLE. The Y chromosome has no identified mutations associated with autoimmune disease.<ref name=Tsokos>{{cite journal |author=Tsokos GC |title=Systemic lupus erythematosus |journal=N. Engl. J. Med. |volume=365 |issue=22 |pages=2110–21 |date=December 2011 |pmid=22129255 |doi=10.1056/NEJMra1100359|citeseerx=10.1.1.1008.5428 }}</ref>

Hormonal mechanisms could explain the increased incidence of SLE in females. The onset of SLE could be attributed to the elevated [[Biology:Hydroxylation|hydroxylation]] of [[Biology:Estrogen|estrogen]] and the abnormally decreased levels of [[Biology:Androgen|androgen]]s in females. In addition, differences in [[Biology:Gonadotropin-releasing hormone|GnRH]] signalling have also shown to contribute to the onset of SLE. While females are more likely to relapse than males, the intensity of these relapses is the same for both sexes.<ref name=":3" />

In addition to hormonal mechanisms, specific genetic influences found on the X chromosome may also contribute to the development of SLE. Studies indicate that the X chromosome can determine the levels of sex hormones. A study has shown an association between [[Medicine:Klinefelter syndrome|Klinefelter syndrome]] and SLE. XXY males with SLE have an abnormal X–Y translocation resulting in the partial triplication of the [[Biology:Pseudoautosomal region|PAR1]] gene region.<ref>{{cite journal | vauthors = Zandman-Goddard G, Peeva E, Shoenfeld Y | year = 2007 | title = Gender and Autoimmunity | journal = Autoimmunity Reviews | volume = 6 | issue = 6| pages = 366–72 | doi=10.1016/j.autrev.2006.10.001| pmid = 17537382 }}</ref>

=== Changing rate of disease ===
The rate of SLE in the United States increased from 1.0 in 1955 to 7.6 in 1974. Whether the increase is due to better diagnosis or to increasing frequency of the disease is unknown.<ref name=Epi2006/>

== History ==
[[Image:Lupus erythematosus, Atlas der Hautkrankheiten.jpg|thumb|A historical drawing of lupus erythematosus as it was once considered as a non-fatal disfiguring skin disease.<ref name="Justiz Vaillant Varacallo 2019 p. ">{{cite | last=Justiz Vaillant | first=AA | last2=Varacallo | first2=M | title=Lupus Erythematosus | chapter=article-24526 | publisher=StatPearls Publishing | publication-place=Treasure Island (FL) | year=2019 | pmid=30571026 | url=http://www.ncbi.nlm.nih.gov/books/NBK535405/ | access-date=2019-12-21 | page=}}</ref>]]
The history of SLE can be divided into three periods: classical, neoclassical, and modern. In each period, research and documentation advanced the understanding and diagnosis of SLE, leading to its classification as an autoimmune disease in 1851, and to the various diagnostic options and treatments now available to people with SLE. The advances made by medical science in the diagnosis and treatment of SLE have dramatically improved the life expectancy of a person diagnosed with SLE.<ref name="Lupus Fdn history">{{cite web|last1=Lupus Foundation of America|url=http://www.lupus.org/answers/entry/what-is-the-history-of-lupus|title=What is the history of lupus?|accessdate=11 October 2014|url-status=live|archiveurl=https://web.archive.org/web/20141104073119/http://www.lupus.org/answers/entry/what-is-the-history-of-lupus|archivedate=4 November 2014}}</ref>

===Etymology===
There are several explanations ventured for the term lupus erythematosus. Lupus is [[Social:Latin|Latin]] for "wolf",<ref>{{cite web|title=Definition in Dictionary.com|url=http://dictionary.reference.com/browse/lupus|publisher=Dictionary.reference.com|accessdate=2012-10-24|url-status=live|archiveurl=https://web.archive.org/web/20121026063456/http://dictionary.reference.com/browse/lupus|archivedate=2012-10-26}}</ref><ref name=Chab2013/> and "erythro" is derived from {{lang|grc|ερυθρός}}, Greek for "red." All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.
# In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face. More likely is that it is derived from the similarity in distribution to lupus vulgaris or chronic facial tuberculosis where the lesions are ragged and punched out and are said to resemble the bite of a wolf.
# Another account claims that the term "lupus" did not come from Latin directly, but from the term for a French style of mask that women reportedly wore to conceal the rash on their faces. The mask is called a "loup," French for "wolf."{{citation needed|date=September 2017}}

=== Classical period ===
The classical period began when the disease was first recognized in the Middle Ages. The term lupus is attributed to 12th-century Italian physician Rogerius Frugard, who used it to describe ulcerating sores on the legs of people.<ref name=Thomas>{{cite book|last1=Thomas, Jr.|first1=Donald E.|title=The Lupus Encyclopedia: A Comprehensive Guide for Patients and Families|date=2014|publisher=Johns Hopkins University Press|location=Baltimore, Maryland|isbn=978-1-4214-0984-9|page=4}}</ref> No formal treatment for the disease existed and the resources available to physicians to help people were limited.<ref>{{cite book|last1=Thomas, Jr.|first1=Donald E.|title=The Lupus Encyclopedia: A Comprehensive Guide for Patients and Families|date=2014|publisher=Johns Hopkins University Press|location=Baltimore, Maryland|isbn=978-1-4214-0984-9|page=463}}</ref>

=== Neoclassical period ===

The neoclassical period began in 1851 when the skin disease which is now known as [[Medicine:Discoid lupus erythematosus|discoid lupus]] was documented by the French physician, Pierre Cazenave. Cazenave termed the illness lupus and added the word erythematosus to distinguish this disease from other illnesses that affected the skin except they were infectious.<ref name=Phillips>{{cite book|last1=Phillips|first1=Robert H.|title=Coping with Lupus: A Practical Guide to Alleviating the Challenges of Systemic Lupus Erythematosus|date=2012|publisher=The Penguin Group|location=New York, NY|isbn=978-1-58333-445-4|pages=[https://archive.org/details/isbn_9781583334454/page/11 11–12]|edition=4th|url=https://archive.org/details/isbn_9781583334454/page/11}}</ref> Cazenave observed the disease in several people and made very detailed notes to assist others in its diagnosis. He was one of the first to document that lupus affected adults from adolescence into the early thirties and that the facial rash is its most distinguishing feature.<ref name=Talbott>{{cite book|last1=Talbott|first1=John H.|editor1-last=Dubois|editor1-first=Edmund L.|title=Lupus Erythematosus: A review of the current status of Discoid and Systemic Lupus Erythematosus|date=1966|publisher=McGraw Hill|location=New York|chapter=Historical Background of Discoid and Systemic Lupus Erythematosus|pages=1–9}}</ref>
 
Research and documentation of the disease continued in the neoclassical period with the work of Ferdinand von Hebra and his son-in-law, Moritz Kaposi. They documented the physical effects of lupus as well as some insights into the possibility that the disease caused internal trauma. Von Hebra observed that lupus symptoms could last many years and that the disease could go "dormant" after years of aggressive activity and then re-appear with symptoms following the same general pattern. These observations led Hebra to term lupus a chronic disease in 1872.<ref>{{cite book|last1=Hebra|first1=Ferdinand|editor1-last=Fagge|editor1-first=C. Hilton|title=Diseases of the skin including the Exanthemata|url=https://archive.org/details/in.ernet.dli.2015.63788|date=1866|publisher=The New Sydenham Society|location=London, England|pages=114–116|edition=Vol. 1}}</ref>

Kaposi observed that lupus assumed two forms: the skin lesions (now known as discoid lupus) and a more aggravated form that affected not only the skin but also caused fever, arthritis, and other systemic disorders in people.<ref>{{cite book|last1=Blau|first1=Sheldon Paul|last2=Schultz|first2=Dodi|title=Lupus:The body against itself|date=1984|publisher=Doubleday & Company Inc.|location=New York|page=6|edition=2nd}}</ref> The latter also presented a rash confined to the face, appearing on the cheeks and across the bridge of the nose; he called this the "butterfly rash". Kaposi also observed those patients who developed the "butterfly rash" (or malar rash) often were afflicted with another disease such as tuberculosis, anemia, or chlorisis which often caused death.<ref name=Talbott /> Kaposi was one of the first people to recognize what is now termed systemic lupus erythematosus in his documentation of the remitting and relapsing nature of the disease and the relationship of skin and systemic manifestations during disease activity.<ref name=Rostein>{{cite journal|last1=Rostein|first1=J.|editor1-last=Kargar|editor1-first=S.|title=Immunosuppresion Systemic Lupus Erythematosus|journal=Rheumatology: An Annual Review|date=1974|volume=5|issue=5 volumes 1967–1974|pages=52–53}}</ref>

The 19th century's research into lupus continued with the work of Sir William Osler who, in 1895, published the first of his three papers about the internal complications of erythema exudativum multiforme. Not all the patient cases in his paper had SLE but Osler's work expanded the knowledge of systemic diseases and documented extensive and critical visceral complications for several diseases including lupus.<ref name=Talbott /> Noting that many people with lupus had a disease that not only affected the skin but many other organs in the body as well, Osler added the word "systemic" to the term lupus erythematosus to distinguish this type of disease from discoid lupus erythematosus.<ref>{{cite book|last1=Carr|first1=Ronald I.|title=Lupus Erythematosus: A Handbook for Physicians, Patients, and their Families|date=1986|publisher=Lupus Foundation of America Inc.|edition=2nd|page=3}}</ref> Osler's second paper noted that reoccurrence is a special feature of the disease and that attacks can be sustained for months or even years. Further study of the disease led to a third paper, published in 1903, documenting afflictions such as arthritis, pneumonia, the inability to form coherent ideas, delirium, and central nervous system damage as all affecting patients diagnosed with SLE.<ref name=Talbott />

=== Modern period ===
The modern period, beginning in 1920, saw major developments in research into the cause and treatment of discoid and systemic lupus. Research conducted in the 1920s and 1930s led to the first detailed pathologic descriptions of lupus and demonstrated how the disease affected the kidney, heart, and lung tissue.<ref name=Wallace>{{cite book|last1=Wallace|first1=Daniel J.|title=The Lupus Book|url=https://archive.org/details/lupusbook00wall|url-access=registration|date=1995|publisher=Oxford University Press|location=New York|page=[https://archive.org/details/lupusbook00wall/page/8 8]}}</ref> A major breakthrough was made in 1948 with the discovery of the LE cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well). Discovered by a team of researchers at the Mayo Clinic, they discovered that the white blood cells contained the nucleus of another cell that was pushing against the white's cell proper nucleus.<ref name=Carr>{{cite book|last1=Carr|first1=Robert I.|title=Lupus Erythematosus: A Handbook for Physicians, Patients and Their Families|date=1986|publisher=Lupus Foundation of America Inc.|edition=2nd|page=15}}</ref> Noting that the invading nucleus was coated with antibody that allowed it to be ingested by a phagocytic or scavenger cell, they named the antibody that causes one cell to ingest another the LE factor and the two nuclei cell result in the LE cell.<ref name=Lahita>{{cite book|last1=Lahita|first2=Robert H.|last2=Phillips|first1=Robert G.|title=Lupus Q&A: Everything you need to know|date=2004|publisher=Penguin Group (USA)|location=New York, NY|isbn=978-1-58333-196-5|pages=[https://archive.org/details/lupusqaeverythin00lah_l84/page/65 65–66]|edition=2nd|url=https://archive.org/details/lupusqaeverythin00lah_l84/page/65}}</ref> The LE cell, it was determined, was a part of an [[Biology:Anti-nuclear antibody|anti-nuclear antibody]] (ANA) reaction; the body produces antibodies against its own tissue. This discovery led to one of the first definitive tests for lupus since LE cells are found in approximately 60% of all people diagnosed with lupus.<ref>{{cite book|last1=Phillips|first1=Robert H.|title=Coping with Lupus: A Practical Guide to Alleviating the Challenges of Systemic Lupus Erythematosus|date=2012|publisher=The Penguin Group|location=New York, NY|isbn=978-1-58333-445-4|page=[https://archive.org/details/isbn_9781583334454/page/24 24]|edition=4th|url=https://archive.org/details/isbn_9781583334454/page/24}}</ref> The LE cell test is rarely performed as a definitive lupus test today as LE cells do not always occur in people with SLE and can occur in individuals with other autoimmune diseases. Their presence can be helpful in establishing a diagnosis but no longer indicates a definitive SLE diagnosis.

The discovery of the LE cell led to further research and this resulted in more definitive tests for lupus. Building on the knowledge that those with SLE had auto-antibodies that would attach themselves to the nuclei of normal cells, causing the immune system to send white blood cells to fight off these "invaders", a test was developed to look for the anti-nuclear antibody (ANA) rather than the LE cell specifically. This ANA test was easier to perform and led not only to a definitive diagnosis of lupus but also many other related diseases. This discovery led to the understanding of what are now known as autoimmune diseases.<ref>{{cite book|last1=Thomas, Jr.|first1=Donald E.|title=The Lupus Encyclopedia: A Comprehensive Guide for Patients and Families|date=2014|publisher=Johns Hopkins University Press|location=Baltimore, USA|isbn=978-1-4214-0984-9|page=26}}</ref>

To ensure that the person has lupus and not another autoimmune disease, the American College of Rheumatology (ACR) established a list of clinical and immunologic criteria that, in any combination, point to SLE. The criteria include symptoms that the person can identify (e.g. pain) and things that a physician can detect in a physical examination and through laboratory test results. The list was originally compiled in 1971, initially revised in 1982, and further revised and improved in 2009.<ref>{{cite book|last1=Thomas, Jr.|first1=Donald E.|title=The Lupus Encyclopedia: A Comprehensive Guide for Patients and Families|date=2014|publisher=Johns Hopkins University Press|location=Baltimore, USA|isbn=978-1-4214-0984-9|pages=17–21}}</ref>

Medical historians have theorized that people with [[Medicine:Porphyria|porphyria]] (a disease that shares many symptoms with SLE) generated folklore stories of vampires and werewolves, due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red stained teeth in severe recessive forms of porphyria (or combinations of the disorder, known as dual, homozygous, or compound heterozygous porphyrias).<ref name="historyof">{{cite journal |author=Hochberg MC |title=The history of lupus erythematosus |journal=Md Med J |volume=40 |issue=10 |pages=871–3 |date=October 1991 |pmid=1943516 }}</ref>

Useful medication for the disease was first found in 1894, when [[Chemistry:Quinine|quinine]] was first reported as an effective therapy. Four years later, the use of [[Chemistry:Salicylic acid|salicylate]]s in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment until the middle of the twentieth century, when Hench discovered the efficacy of [[Biology:Corticosteroid|corticosteroid]]s in the treatment of SLE.<ref name="historyof"/>

==Research==
A study called BLISS-76 tested the drug [[Chemistry:Belimumab|belimumab]], a fully human [[Biology:Monoclonal antibody|monoclonal]] anti-[[Biology:B-cell activating factor|BAFF]] (or anti-BLyS) antibody.<ref name="Vincent FB, Morand EF and Mackay F 2012 293–303"/> BAFF stimulates and extends the life of B lymphocytes, which produce antibodies against foreign and self cells.<ref>{{cite journal|last1=Jordan|first1=Natasha|last2=D’Cruz|first2=David P|title=Belimumab for the treatment of systemic lupus erythematosus|journal=Expert Review of Clinical Immunology|date=29 December 2014|volume=11|issue=2|pages=195–204|doi=10.1586/1744666X.2015.996550|pmid=25543845}}</ref> It was approved by the FDA in March 2011.<ref name=Benlysta/> Genetically engineered immune cells are also being studied in animal models of the disease as of 2019.<ref>{{cite web |last1=Couzin-FrankelMar. 6 |first1=Jennifer |title=Genetically engineered immune cells wipe out lupus in mice |url=https://www.sciencemag.org/news/2019/03/genetically-engineered-immune-cells-wipe-out-lupus-mice |website=Science {{!}} AAAS |accessdate=8 May 2019 |language=en |date=6 March 2019}}</ref>

==See also==
* [[Medicine:Canine discoid lupus erythematosus|Canine discoid lupus erythematosus]] in dogs

==References==
{{Reflist}}

==External links==
{{Medical condition classification and resources
  |ICD10          = {{ICD10|M|32||m|30}}
  |ICD9           = {{ICD9|710.0}}
  |DiseasesDB     = 12782
  |OMIM           = 152700
  |MedlinePlus    = 000435
  |eMedicineSubj  = med
  |eMedicineTopic = 2228
  |eMedicine_mult = {{eMedicine2|emerg|564}}
  |MeshID         = D008180
}}

*{{curlie|Health/Conditions_and_Diseases/Musculoskeletal_Disorders/Connective_Tissue/Lupus}}
*[https://www.niams.nih.gov/health-topics/lupus Systemic Lupus Erythematosus] at National Institute of Arthritis and Musculoskeletal and Skin Diseases
{{Systemic connective tissue disorders}}
{{Lupus nephritis}}

{{DEFAULTSORT:Systemic Lupus Erythematosus}}
[[Category:Autoimmune diseases]]
[[Category:Disorders causing seizures]]

{{Sourceattribution|Systemic lupus erythematosus|1}}