Systemic lupus erythematosus 18427 226100129 2008-07-16T20:42:34Z Academic Challenger 30528 Reverted edits by [[Special:Contributions/71.119.20.144|71.119.20.144]] ([[User talk:71.119.20.144|talk]]) to last version by Cassie Puma {{Infobox_Disease |Name = Lupus erythematosus |Caption = |ICD10 = {{ICD10|L|93||l|80}}, {{ICD10|M|32||m|30}} |ICD9 = {{ICD9|710.0}} |DiseasesDB = 12782 |ICDO = |OMIM = 152700 |MedlinePlus = 000435 |eMedicineSubj = med |eMedicineTopic = 2228 |eMedicine_mult = {{eMedicine2|emerg|564}} |MeshID = D008180 }} '''Systemic lupus erythematosus''' ('''SLE''' or '''lupus''', {{pron-en|sɪˈstɛmɪk ˈluːpəs ˌɛrəˌθiməˈtoʊsəs}}) is a chronic [[Autoimmunity|autoimmune disease]] that can be fatal, though with recent medical advances, fatalities are becoming increasingly rare. As with other [[Autoimmunity|autoimmune diseases]], the [[immune system]] attacks the body’s cells and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but most often harms the [[heart]], [[joint]]s, [[skin]], [[lung]]s, [[blood vessel]]s, [[liver]], [[kidney]]s, and [[Nervous system#Vertebrates|nervous system]]. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions. Lupus can occur at any age, and is most common in women, particularly of non-European descent.<ref>{{cite web |url=http://www.lupus.org/education/stats.html#1 |title=LUPUS FOUNDATION OF AMERICA |accessdate=2007-07-04 |format= |work=}}</ref> Lupus is treatable [[Symptomatic treatment|symptomatically]], mainly with [[corticosteroid]]s and [[immunosuppression|immunosuppressants]], though there is currently no cure. Survival in patients with SLE in the United States, Canada, and Europe is approximately 95% at 5 years, 90% at 10 years, and 78% at 20 years.<ref>[http://www.accessmedicine.com/content.aspx?aID=2859070 Harrison's Internal Medicine, 17th ed. Chapter 313. Systemic Lupus Erythematosus.</ref> ==Classification== ''Lupus'' is a chronic [[Autoimmunity|autoimmune disease]]. Clinically, it can affect multiple organ systems, including the heart, skin, joints, kidneys, and nervous system. There are several types of lupus; generally, when the word "lupus" alone is used, it refers to '''systemic lupus erythematosus''' or '''SLE''', as discussed in this article. Other types include: * '''[[Drug-induced lupus erythematosus]]''', a drug-induced form of SLE; this type of lupus can occur equally in either sex. * '''[[Lupus nephritis]]''', an inflammation of the [[kidney]]s caused by SLE. * '''Discoid lupus erythematosus''', a skin disorder that causes a red, raised rash on the face and scalp. Discoid lupus occasionally (1–5%) develops into SLE.<ref>[http://www.skinsite.com/info_discoid_lupus_erythematosus.htm Discoid Lupus Erythematosus]</ref> * '''Subacute cutaneous lupus erythematosus''', which causes nonscarring skin [[lesions]] on patches of skin exposed to sunlight.<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}}</ref> * '''Neonatal lupus''', a rare disease affecting babies born to women with SLE, [[Sjögren's syndrome]], or sometimes no autoimmune disorder. It is theorized that maternal antibodies attack the fetus, causing skin rash; liver problems; low blood counts, which gradually fade; and heart block, leading to [[bradycardia]].<ref name=niams/> ==Signs and symptoms== SLE is one of several diseases known as "the great imitators"<ref>[http://healthcare.utah.edu/healthtools/articles/lupus.html Lupus: The Great Imitator]</ref> because its symptoms vary so widely, it often mimics or is mistaken for other illnesses and because the symptoms come and go unpredictably. Diagnosis can be elusive, with patients sometimes suffering unexplained symptoms and untreated SLE for years. Common initial and chronic complaints are [[fever]], [[malaise]], [[arthralgia|joint pains]], [[myalgia]]s, and [[Fatigue (medical)|fatigue]]. Because they are so often seen 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 (see below), however, they are considered suggestive.<ref name=mayo_lupussymptoms>{{cite web|title=Lupus: Symptoms - MayoClinic.com|url=http://www.mayoclinic.com/health/lupus/DS00115/DSECTION=symptoms|accessdate=2008-07-14}}</ref> ===Common symptoms explained=== ;Dermatological manifestations: As many as 30% of patients present with some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic [[malar rash]] (or ''butterfly rash'') associated with the disease. Patients may present with discoid lupus (thick, red scaly patches on the skin). [[Alopecia]]; mouth, nasal, and vaginal [[mouth ulcer|ulcers]]; and lesions on the skin are also possible manifestations. ;Musculoskeletal manifestations: Patients most often seek medical attention for [[joint pain]], with the small joints of the hand and wrist usually affected, although all joints are at risk. The Lupus Foundation of America estimates that more than 90 percent will experience joint and/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] Lupus Foundation of America</ref> Unlike [[rheumatoid arthritis]], lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of the hands and feet.<ref name="lfa1"/> ;Hematological manifestations: [[Anemia]] and iron deficiency may develop in as many as half of patients. Low [[platelet]] and [[white blood cell]] counts may be due to the disease or a side effect of pharmacological treatment. Patients may have an association with [[Antiphospholipid syndrome|antiphospholipid antibody syndrome]] (a thrombotic disorder) wherein autoantibodies to phospholipids are present in the patient's serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT (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 lupus is the [[anticardiolipin antibody]], which can cause a false positive test for [[syphilis]]. ;Cardiac manifestations: Patients may present with inflammation of various parts of the [[heart]], such as [[pericarditis]], [[myocarditis]], and [[endocarditis]]. The endocarditis of SLE is characteristically noninfective ([[Libman-Sacks endocarditis]]) and involves either the [[mitral valve]] or the [[tricuspid valve]]. [[Atherosclerosis]] also tends to occur more often and advances more rapidly in SLE patients than in the general population.<ref>{{cite journal | author=Yu Asanuma, M.D., Ph.D., Annette Oeser, B.S., Ayumi K. Shintani, Ph.D., M.P.H., Elizabeth Turner, M.D., Nancy Olsen, M.D., Sergio Fazio, M.D., Ph.D., MacRae F. Linton, M.D., Paolo Raggi, M.D., and C. Michael Stein, M.D. | title=Premature coronary-artery atherosclerosis in systemic lupus erythematosus | journal=New England Journal of Medicine | volume=349 | issue=Dec. 18 | year=2003| pages=2407–2414 | doi = 10.1056/NEJMoa035611 | pmid = 14681506 [http://content.nejm.org/cgi/content/abstract/349/25/2407 Abstract] (full text requires registration) }}</ref><ref>{{cite journal | author=Bevra Hannahs Hahn, M.D. | title=Systemic lupus erythematosus and accelerated atherosclerosis | journal=New England Journal of Medicine | volume=349 | issue=Dec. 18 | year=2003 | pages=2379–2380 | url = http://content.nejm.org/cgi/content/full/349/25/2379 | pmid =14681501 [http://content.nejm.org/cgi/content/extract/349/25/2379 Extract] (full text requires registration) | doi=10.1056/NEJMp038168 }}</ref><ref> {{cite journal | author=Mary J. Roman, M.D., Beth-Ann Shanker, A.B., Adrienne Davis, A.B., Michael D. Lockshin, M.D., Lisa Sammaritano, M.D., Ronit Simantov, M.D., Mary K. Crow, M.D., Joseph E. Schwartz, Ph.D., Stephen A. Paget, M.D., Richard B. Devereux, M.D., and Jane E. Salmon, M.D. | title=Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus | journal=New England Journal of Medicine | volume=349 | issue=Dec. 18 | year=2003 | pages=2399–2406 | doi = 10.1056/NEJMoa035471 | pmid = 14681505 [http://content.nejm.org/cgi/content/abstract/349/25/2399 Abstract] (full text requires registration) }}</ref> ;Pulmonary manifestations: Lung and pleura inflammation can cause [[Pleurisy|pleuritis]], [[pleural effusion]], lupus pneumonitis, chronic diffuse interstitial lung disease, [[pulmonary hypertension]], [[Pulmonary embolism|pulmonary emboli]], [[pulmonary hemorrhage]] and shrinking lung syndrome. ;Hepatic involvement: See [[autoimmune hepatitis]]. ;Renal involvement: Painless [[hematuria]] or [[proteinuria]] may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with [[lupus nephritis]], leading to acute or end stage [[renal failure]]. Because of early recognition and management of SLE, end stage renal failure occurs in less than 5% of patients. :Histologically, a hallmark of SLE is membranous [[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 |format= |work=}}</ref> This finding is due to immune complex deposition along the [[glomerular basement membrane]], leading to a typical granular appearance in [[immunofluorescence]] testing. ;Neurological manifestations: About 10% of patients may present with [[seizure]]s or [[psychosis]]. One-third may test positive for abnormalities in the [[cerebrospinal fluid]]. ;T-cell abnormalities: Abnormalities in [[T cell]]-signaling are associated with SLE, including a deficiency in [[CD45]] [[phosphatase]] and increased expression of [[CD154|CD40 ligand]]. ;Other rarer manifestations: [[gastroenteritis|Lupus gastroenteritis]], [[pancreatitis|lupus pancreatitis]], [[cystitis|lupus cystitis]], [[autoimmune]] [[Otitis interna|inner ear disease]], [[parasympathetic|parasympathetic dysfunction]], [[vasculitis|retinal vasculitis]], and [[vasculitis|systemic vasculitis]]. Other abnormalities include: *Increased expression of [[FcεRI]]γ, which replaces the sometimes deficient TCR [[ζ]] chain *Increased and sustained calcium levels in [[T cell]]s *Moderate increase of [[inositol triphosphate]] *Reduction in [[Protein kinase C|PKC]] phosphorylation *Reduction in Ras-[[Mitogen-activated protein kinase|MAP kinase]] signaling *Deficiencies in [[protein kinase]] A I activity ==Causes== ;Transmission: In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. SLE is triggered by environmental factors that are unknown (but probably include viruses) in people with certain combinations of genes in their immune system. "All the key components of the immune system are involved in the underlying mechanisms" of SLE, according to Rahman, and SLE is the prototypical autoimmune disease. The immune system must have a balance ([[homeostasis]]) between being sensitive enough to protect against infection, and being too sensitive and attacking the body's own proteins (autoimmunity). From an evolutionary perspective, according to Crow, the population must have enough genetic diversity to protect itself against a wide range of possible infection; some genetic combinations result in autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the [[apoptosis|destruction]] of cells and expose their DNA, [[histones]], and other proteins, particularly parts of the cell nucleus. Because of genetic variations in different components of the immune system, in some people the immune system attacks these nuclear-related proteins and produces antibodies against them. Ultimately, these antibody complexes damage blood vessels in critical areas of the body, such as the [[glomeruli]] of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links. <ref>{{cite journal |author=Anisur Rahman and David A. Isenberg |title=Review Article: Systemic Lupus Erythematosus |journal=N Engl J Med |volume=358 |issue=9 |pages=929–939 |year=2008 |date=February 28, 2008 |pmid=18305268 |url=http://content.nejm.org/cgi/content/full/358/9/929 |doi=10.1056/NEJMra071297}}</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 |year=2008 |date=February 28, 2008 |pmid=18204099 |url=http://content.nejm.org/cgi/content/full/358/9/956 |doi=10.1056/NEJMe0800096}}</ref><ref>{{cite journal |author=Geoffrey Hom, Robert R. Graham, Barmak Modrek, et al. |title=Association of Systemic Lupus Erythematosus with C8orf13–BLK and ITGAM–ITGAX |journal=N Engl J Med |volume=358 |issue=9 |pages=900–909 |year=2008 |date=February 28, 2008 |pmid=18204098 |url=http://content.nejm.org/cgi/content/full/358/9/900 |doi=10.1056/NEJMoa0707865}}</ref> SLE is a chronic [[inflammation|inflammatory]] disease believed to be a [[Hypersensitivity#Type 3 - immune complex|type III hypersensitivity]] response with potential [[Hypersensitivity#Type 2 - antibody-dependent|type II]] involvement.<ref>[http://pathmicro.med.sc.edu/ghaffar/hyper00.htm University of South Carolina School of Medicine lecture notes, Immunology, Hypersensitivity reactions. General discussion of hypersensitivity, not specific to SLE.]</ref> ;Genetics: The first mechanism may arise genetically. Research indicates that SLE may have a [[genetics|genetic]] link. Lupus does run in families, but no single "lupus gene" has yet been identified. Instead, multiple genes appear to influence a person's chance of developing lupus when triggered by environmental factors. The most important genes are located on [[Chromosome 6 (human)|chromosome 6]], where mutations may occur randomly (''de novo'') or may be inherited. Additionally, people with SLE have an altered RUNX-1 binding site, which may be either cause or contributor (or both) to the condition. Altered binding sites for RUNX-1 have also been found in people with [[psoriasis]] and [[rheumatoid arthritis]]. ;Environmental triggers: The second mechanism may be due to environmental factors. These factors may not only exacerbate existing lupus conditions but also trigger the initial onset. They include certain medications (such as some [[antidepressant]]s and [[antibiotic]]s), extreme stress, exposure to sunlight, hormones, and infections. Some researchers have sought to find a connection between certain infectious agents ([[virus]]es and [[bacteria]]), but no pathogen can be consistently linked to the disease. UV radiation has been shown to trigger the photosensitive lupus rash, but some evidence also suggests that UV light is capable of altering the structure of the DNA, leading to the creation of autoantibodies. Some researchers have found that women with [[silicone]] gel-filled [[breast implant]]s have produced antibodies to their own [[collagen]], but it is not known how often these antibodies occur in the general population, and there is no data that show that these antibodies cause [[connective tissue disease]]s such as lupus. ;Drug reactions: [[Drug-induced lupus erythematosus]] is a reversible condition that usually occurs in patients being treated for a long-term illness. Drug-induced lupus mimics systemic lupus. However, symptoms of drug-induced lupus generally disappear once a patient is taken off the medication that triggered the episode. There are about 400 medications currently in use that can cause this condition, though the most common drugs are [[procainamide]], [[hydralazine]], [[quinidine]] and [[Phenytoin]]. ;Non-SLE forms of lupus: Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of skin rash on the face, neck, or scalp. Often an [[antinuclear antibody]] (ANA) test for discoid patients is negative or a low-titer positive. About 1–5% of discoid lupus patients eventually develop SLE. <!---Note that the discoid lupus on wikipedia refers to the canine variant only, and the human version redirects to this article---> ;Clearance deficiency: [[Image:Picture1 englisch.jpg|thumb|Clearance deficiency.]]The exact mechanisms for the development of systemic lupus erythematosus (SLE) are still unclear, since the pathogenesis is a multifactorial event. Beside discussed causations, impaired clearance of dying cells is a potential pathway for the development of this systemic [[autoimmune disease]]. This includes deficient phagocytic activity and scant serum components in addition to increased [[apoptosis]]. [[Monocytes]] isolated from [[whole blood]] of SLE patients show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBM), which are found in the [[germinal centre]]s of [[lymph nodes]], even show a definitely different morphology in patients with SLE; they are smaller or scarce and die earlier. Serum components like [[Complement system|complement]] factors, [[C-reactive protein|CRP]], and some [[glycoproteins]] are furthermore decisively important for an efficiently operating phagocytosis. In patients, these components are often missing, diminished, or inefficient. The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary [[necrosis]] of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential [[autoantigens]] as well as internal danger signals, inducing maturation of [[dendritic cells]] (DC), since they have lost their membranes' integrity. Increased appearance of apoptotic cells also simulates inefficient clearance. That leads to maturation of DC and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules. [[Autoimmunity]] possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and [[T cell]] tolerance for apoptotic cells is abrogated, and the [[lymphocytes]] get activated by these autoantigens; [[inflammation]] and the production of autoantibodies by [[plasma cells]] is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in patients with cutaneous lupus erythematosus (CLE).<ref>{{cite journal |author=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 |url=}}</ref> [[Image:Picture2 englisch.jpg|thumb|Germinal centres.]] '''Accumulation in germinal centres (GC)''' In healthy conditions, apoptotic lymphocytes are removed in germinal centres by specialised phagocytes, the tingible body macrophages (TBM); that’s why no free apoptotic and potential autoantigenic material can be seen. In some patients with SLE, [[accumulation]] of apoptotic [[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 [[bone marrow]]-derived DC, neither take it up nor present it via [[Major histocompatibility complex|MHC]] molecules. Autoreactive [[B cells]] can accidentally emerge during [[somatic hypermutation]] and migrate into the GC light zone. Autoreactive B cells, maturated coincidentally, normally don’t receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells, a chronic [[autoimmune disease]] may be the consequence. ==Pathophysiology== One manifestation of lupus is abnormalities in apoptosis, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning. ===Abnormalities in apoptosis=== *[[Apoptosis]] is increased in [[monocyte]]s and [[keratinocyte]]s; *[[Gene expression|Expression]] of [[FAS ligand|Fas]] by [[B cell]]s and [[T cell]]s is increased; *There are correlations between the apoptotic rates of lymphocytes and disease activity. Tingible body macrophages (TBMs) are large phagocytic cells in the [[germinal center]]s of secondary [[lymph node]]s; they express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after [[somatic hypermutation]]. In some patients with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. [[Dendritic 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 [[somatic hypermutation]].<ref>{{cite journal | author=Gaipl, U S; Kuhn, A; Sheriff, A; Munoz, L E; Franz, S; Voll, R E; Kalden, J R; Herrmann, M | title=Clearance of apoptotic cells in human SLE | journal=Current directions in autoimmunity | volume=9 | issue= | year=2006 | pages=173–87 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16394661&dopt=Abstract | pmid = : 1639466 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16394661&dopt=Abstract Abstract] (full text requires registration) }}</ref> ==Diagnosis== [[Image:Lupus band test.jpg|thumb|200px|right|Microphotograph of a [[histology|histological section]] of human skin prepared for direct [[immunofluorescence]] using an anti-IgG antibody. The skin is from a patient 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 [[Epidermis (skin)|epidermal]] cells (antinuclear antibodies are present).]] Some physicians make a diagnosis on the basis of the ACR classification criteria (see below). The criteria, however, were established mainly for use in scientific research (i.e., inclusion in [[randomized controlled trial]]s), and patients may have lupus but never meet the full criteria. [[Antinuclear antibody]] testing and anti-''extractable nuclear antigen'' ([[anti-ENA]]) form the mainstay of [[Serology|serologic]] testing for lupus. Antiphospholipid antibodies occur more often in SLE and can predispose for [[thrombosis]]. More specific are the [[LSm#History|anti-Smith]] and anti-dsDNA antibodies. Other tests routinely performed in suspected SLE are [[complement system]] levels (low levels suggest consumption by the immune system), [[electrolyte]]s and [[renal function]] (disturbed if the kidney is involved), [[Liver function test|liver enzyme]]s, and a [[complete blood count]]. Previously, the lupus erythematosus (LE) cell test was not commonly used for diagnosis because those LE cells are only found in 50–75% of SLE patients, and are also found in some patients 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>[http://www.nlm.nih.gov/medlineplus/ency/article/003635.htm NIM encyclopedic article on the LE cell test]</ref> ===Diagnostic criteria=== The American College of Rheumatology (ACR) established eleven criteria in 1982,<ref>[http://www.rheumatology.org/publications/classification/index.asp?aud=mem Rheumatology.org article on the classification of rheumatic diseases]</ref> which were revised in 1997<ref>[http://www.rheumatology.org/publications/classification/SLE/1982SLEupdate.asp?aud=mem Revision of Rheumatology.org's diagnostic criteria]</ref> as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individual patients and do not do well in that capacity. For inclusion in clinical trials, patients must meet the following three criteria to be classified as having SLE: (i) patient must present with four of the below eleven symptoms, (ii) either simultaneously or serially, (iii) during a ''given period of observation''. # '''S'''erositis: [[Pleurisy|Pleuritis]] (inflammation of the membrane around the lungs) or [[pericarditis]] (inflammation of the membrane around the heart); [[sensitivity (tests)|sensitivity]] = 56%; [[specificity (tests)|specificity]] = 86% (pleural is more sensitive; cardiac is more specific).<ref name="pmid3060613"/> # '''O'''ral ulcers (includes oral or nasopharyngeal ulcers). # [[Arthritis|'''A'''rthritis]]: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; [[sensitivity (tests)|sensitivity]] = 86%; [[specificity (tests)|specificity]] = 37%.<ref name="pmid3060613"/> # [[Photodermatitis|'''P'''hotosensitivity]] (exposure to ultraviolet light causes rash); [[sensitivity (tests)|sensitivity]] = 43%; [[specificity (tests)|specificity]] = 96%.<ref name="pmid3060613"/> # '''B'''lood—hematologic disorder—[[hemolytic anemia]] (low [[red blood cell]] count) or [[leukopenia]] (white blood cell count<4000/µl), [[lymphopenia]] (<1500/µl) or [[thrombocytopenia]] (<100000/µl) in the absence of offending drug; [[sensitivity (tests)|sensitivity]] = 59%; [[specificity (tests)|specificity]] = 89%.<ref name="pmid3060613"/> Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE. # '''R'''enal disorder: More than 0.5g per day [[Proteinuria|protein in urine]] or cellular [[Urinary casts|casts]] seen in urine under a microscope; [[sensitivity (tests)|sensitivity]] = 51%; [[specificity (tests)|specificity]] = 94%.<ref name="pmid3060613"/> # [[Antinuclear antibody|'''A'''ntinuclear antibody]] test positive; [[sensitivity (tests) |sensitivity]] = 99%; [[specificity (tests)|specificity]] = 49%.<ref name="pmid3060613"/> # '''I'''mmunologic disorder: Positive [[LSm#History|anti-Smith]], anti-ds DNA, [[Antiphospholipid syndrome|antiphospholipid antibody]], and/or false positive [[serology|serological]] test for [[syphilis]]; [[sensitivity (tests)|sensitivity]] = 85%; [[specificity (tests)|specificity]] = 93%.<ref name="pmid3060613"/> Presence of anti-ss DNA in 70% of patients (though also positive in patients with rheumatic disease and healthy persons<ref>[http://patients.uptodate.com/topic.asp?file=dx_rheum/18305 UpToDate Patient information article on DNA antibodies]</ref>). # '''N'''eurologic disorder: [[Seizure]]s or [[psychosis]]; [[sensitivity (tests)|sensitivity]] = 20%; [[specificity (tests)|specificity]] = 98%.<ref name="pmid3060613"/> # [[Malar rash|'''M'''alar rash]] (rash on cheeks); [[sensitivity (tests)|sensitivity]] = 57%; [[specificity (tests)|specificity]] = 96%.<ref name="pmid3060613"/> # '''D'''iscoid rash (red, scaly patches on skin that cause scarring); [[sensitivity (tests)|sensitivity]] = 18%; [[specificity (tests)|specificity]] = 99%.<ref name="pmid3060613"/> A useful mnemonic for these 11 criteria is ''SOAP BRAIN MD'': '''S'''erositis (8), '''O'''ral ulcers (4), '''A'''rthritis (5), '''P'''hotosensitivity (3), '''B'''lood Changes (9), '''R'''enal involvement (proteinuria or casts) (6), '''A'''NA (10), '''I'''mmunological changes (11), '''N'''eurological signs (seizures, frank psychosis) (7), '''M'''alar Rash (1), '''D'''iscoid Rash (2). Some patients, especially those with [[antiphospholipid syndrome]], may have SLE without four criteria, and SLE is associated with manifestations other than those listed in the criteria.<ref name="pmid12892393">{{cite journal |author=Asherson RA, Cervera R, de Groot PG, ''et al'' |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| doi = 10.1191/0961203303lu394oa <!--Retrieved from CrossRef by DOI bot-->}}</ref><ref name="pmid15608315">{{cite journal |author=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}}</ref><ref name="pmid14644846">{{cite journal |author=Hughes GR, Khamashta MA |title=Seronegative antiphospholipid syndrome |journal=Ann. Rheum. Dis. |volume=62 |issue=12 |pages=1127 |year=2003 |pmid=14644846| doi = 10.1136/ard.2003.006163 <!--Retrieved from CrossRef by DOI bot-->}}</ref> ====Alternative criteria==== [[Recursive partitioning]] has been used to identify more parsimonious criteria.<ref name="pmid3060613">{{cite journal |author=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: 1. Simplest classification tree: LSE is diagnosed if the patient has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or [[malar rash]]. * [[sensitivity (tests)|sensitivity]] = 92% * [[specificity (tests)|specificity]] = 92% 2. Full classification tree: Uses 6 criteria. * [[sensitivity (tests)|sensitivity]] = 97% * [[specificity (tests)|specificity]] = 95% Other alternative criteria have been suggested.<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== As lupus erythematosus is a chronic disease with no known cure, treatment is restricted to dealing with the [[Symptomatic treatment|symptoms]]. Essentially, this involves preventing flares and reducing their severity and duration when they occur. There are several means of preventing and dealing with flares, including drugs, alternative medicine, and lifestyle changes. ===Drug therapy=== Due to the variety of symptoms and organ system involvement with lupus patients, the severity of the SLE in a particular patient must be assessed in order to successfully treat SLE. Mild or remittent disease can sometimes be safely left untreated. If required, [[nonsteroidal anti-inflammatory drug]]s and [[malaria|antimalarials]] may be used. [[Disease-modifying antirheumatic drug]]s (DMARDs) are used preventively to reduce the incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with [[corticosteroids]]. DMARDs commonly in use are antimalarials and [[immunosuppressants]] (e.g., [[methotrexate]] and [[azathioprine]]). [[Hydroxychloroquine]] (trade name Plaquenil) is an FDA-approved antimalarial used for constitutional, cutaneous, and articular manifestations, while [[cyclophosphamide]] (trade names Cytoxan and Neosar) is used for severe [[glomerulonephritis]] or other organ-damaging complications. In 2005, [[mycophenolic acid]] (trade name CellCept) became accepted for treatment of lupus nephritis. In more severe cases, medications that modulate the immune system (primarily corticosteroids and [[immunosuppressive drug|immunosuppressants]]) are used to control the disease and prevent recurrence of symptoms (known as flares). Patients who require steroids frequently may develop [[obesity]], [[diabetes mellitus]], [[diabetes]], and [[osteoporosis]]. Depending on the dosage, corticosteroids can cause other side effects, such as a puffy face, an unusually large appetite, and difficulty sleeping. Those side effects can subside if and when the large initial dosage is reduced, but long-term use of even low doses can cause elevated [[blood pressure]] and [[cataracts]]. Due to these side effects, steroids are avoided if possible. Since a large percentage of lupus patients suffer from varying amounts of [[chronic pain]], stronger prescription [[analgesics]] may be used if over-the-counter drugs (mainly nonsteroidal anti-inflammatory drugs) do not provide effective relief. Moderate pain in lupus patients is typically treated with mild prescription opiates such as [[dextropropoxyphene]] (trade name Darvocet) and [[co-codamol]] (trade name Tylenol #3). Moderate to severe chronic pain is treated with stronger opioids, such as [[hydrocodone]] (trade names Lorcet, Lortab, Norco, Vicodin, Vicoprofen) or longer-acting continuous-release [[opioids]], such as [[oxycodone]] (trade name OxyContin), [[MS Contin]], or [[Methadone]]. The [[Fentanyl]] Duragesic Transdermal patch is also a widely used treatment option for the chronic pain of lupus complications because of its long-acting timed release and ease of use. When opioids are used for prolonged periods, drug tolerance, chemical dependency, and (rarely) addiction may occur. Opiate addiction is not typically a concern for lupus patients, since the condition is not likely to ever completely disappear. Thus, lifelong treatment with opioids is fairly common in lupus patients who exhibit chronic pain symptoms, accompanied by periodic [[titration]] that is typical of any long-term opioid regimen. ===Lifestyle changes=== Other measures, such as avoiding sunlight or covering up with sun-protective clothing, can also be effective in preventing photosensitivity problems. Weight loss is also recommended in overweight and obese patients to alleviate some of the effects of the disease, especially where joint involvement is significant. ==Prevention== Lupus is not understood well enough to be prevented, but when the disease develops, quality of life can be improved through flare prevention. The warning signs of an impending flare include increased fatigue, pain, rash, fever, abdominal discomfort, headache, and dizziness. Early recognition of warning signs and good communication with a doctor can help individuals with lupus remain active, experience less pain, and reduce medical visits.<ref name=niams/> ===Complications during pregnancy=== While most infants born to mothers with lupus are healthy, pregnant mothers with SLE should remain under a doctor's 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 during pregnancy, and proper treatment can maintain the health of the mother longer. Women pregnant and known to have the antibodies for anti-Ro (SSA) or anti-La (SSB) should have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.<ref name=niams/> ===Prognosis=== In the 1950s, most patients diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% of patients now survive for more than ten years, and many can live relatively asymptomatically. The most common cause of death is [[infectious disease|infection]] due to [[immunosuppression]] as a result of medications used to manage the disease. Prognosis is normally worse for men and children than for women; fortunately, if symptoms are present after age 60, the disease tends to run a more benign course. The ANA is the most sensitive screening test, while [[LSm#History|anti-Sm (anti-Smith)]] is the most specific. The ds-DNA (double-stranded [[DNA]]) antibody is also fairly specific and often fluctuates with disease activity; the ds-DNA titer is therefore sometimes useful to diagnose or monitor acute flares or response to treatment.<ref>[EARLY STEROIDS MAY PREVENT RELAPSES IN LUPUS, P Jarman (Published in Journal Watch (General) [[July 18]], [[1995]])</ref> ==Epidemiology== Previously believed to be a rare disease, lupus has seen an increase in awareness and education since the 1960s. This has helped many more patients get an accurate diagnosis, making it possible to estimate the number of people with lupus with some certainty. In the United States alone, it is estimated that between 270,000 and 1.5 million people have lupus, making it more common than [[cystic fibrosis]] or [[cerebral palsy]]. The disease affects both females and males, though young women are diagnosed nine times more often than men. SLE occurs with much greater severity among African-American women, who suffer more severe symptoms as well as a higher mortality rate.<ref>[http://nmanet.org/images/uploads/Great_Imitator.pdf#search=%22lupus%20great%20imitator%22 Lupus and African-American women]</ref> Worldwide, a conservative estimate states that over 5 million people have lupus. Although SLE can occur in anyone, at any age, it is most common in women of childbearing age. It affects 1 in 4000 people in the United States, again with women becoming afflicted far more often than men. The disease appears to be more prevalent in women of African, Asian, Hispanic, and Native American origin, but this may be due to socioeconomic factors. People with relatives who suffer from SLE, [[rheumatoid arthritis]], or [[thrombotic thrombocytopenic purpura]] are at a slightly higher risk than the general population. ==History== Medical historians have theorized that people with [[porphyria]] (a disease that shares many symptoms with lupus) 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). The history of lupus erythematosus can be divided into three periods: classical, neoclassical, and modern. The classical period began when the disease was first recognized in the [[Middle Ages]] and saw the description of the dermatological manifestation of the disorder. The term ''lupus'' is attributed to [[12th-century]] [[physician]] [[Rogerius (physician)|Rogerius]], who used it to describe the classic malar rash. The neoclassical period was heralded by [[Móric Kaposi]]'s recognition in 1872 of the systemic manifestations of the disease. The modern period began in 1948 with the discovery of the LE cell (the ''lupus erythematosus'' cell—a misnomer, as it occurs with other diseases as well) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment. Useful medication for the disease was first found in 1894, when [[quinine]] was first reported as an effective therapy. Four years later, the use of [[Salicylic acid|salicylate]]s in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment to patients until the middle of the twentieth century, when Hench discovered the efficacy of [[corticosteroid]]s in the treatment of SLE. In modern times, the disease has received a degree of notoriety due to it becoming the subject of a running joke on the popular television series [[House, M.D.]]. In each episode when a patient with an undiagnosable condition is presented, Lupus is routinely suggested as a possible early diagnosis, despite the fact that it seldom is the answer. ===Origins of "lupus erythematosus"=== {{Unreferencedsection|date=May 2008}} There are several explanations ventured for the term '''lupus erythematosus'''. Lupus is [[Latin]] for wolf, and "erythro" is derived from ερυθρός{{Polytonic|}}, Greek for "red." <!---anyone know what matosus means?---> 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. # In other accounts, doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches. # Another account claims that the term "lupus" did not come from Latin at all, 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." # Another common explanation for the term is that the disease's course involves repeated attacks like those of a voracious predator, leaving behind the red blotches. ==Notable patients== * [[Louisa May Alcott]], American author. * [[Inday Ba]] (also known as N'Deaye Ba), a Swedish-born actress who died from complications of lupus at age 32. * [[Donald Byrne]], American [[chess]] player who died from complications of lupus in 1976. * [[J Dilla]] (also known as Jay Dee), a hip-hop producer and beatmaker who died of the disease in 2006. * Caroline Dorough-Cochran, sister of [[Howie Dorough|Howie D.]] of the [[Backstreet Boys]], who founded the Dorough Lupus Foundation in her memory. * [[Hugh Gaitskell]], British politician. * [[Sophie Howard]], British glamour model. * [[Michael Jackson]], pop superstar, diagnosed with the disease in 1984. * [[Charles Kuralt]], former anchor of ''[[CBS Sunday Morning]]'', died of the disease in 1997. * [[Ferdinand Marcos]], former Philippine president, who died from complications of lupus in 1989. * [[Mary Elizabeth McDonough]], American actress. * [[Flannery O'Connor]], American fiction writer who died of the disease in 1964. * [[Elaine Paige]], British actress and singer. * [[Tim Raines]], former major league baseball player, primarily with the [[Montreal Expos]] and [[Chicago White Sox]]. * [[Mercedes Scelba-Shorte]], ''[[America's Next Top Model]]'' Season Two runner-up and model. * [[Seal (musician)|Seal]], singer (discoid lupus of the face, leading to scarring) * [[LSm#History|Stephanie Smith]], artist who died of SLE complications in 1969 at the age of 22. The anti-Smith (or anti-Sm) antigen was discovered in her and is the basis of a SLE diagnostic test. * [[Ray Walston]], character actor. <!---Please do not add references to House M.D. or other 'within media' references to the Lupus page—the references add very little merit to an already long article. Thanks! ---> ==See also== * [[Abzyme]] * [[Alliance for Lupus Research]] * [[Antinuclear antibody]] * [[Canine discoid lupus erythematosus]] in dogs * [[Lupus Canada]] * [[Lupus Foundation of America]] ==References== {{Reflist|2}} ==External links== *{{DMOZ|Health/Conditions_and_Diseases/Musculoskeletal_Disorders/Connective_Tissue/Lupus}} *[http://www.lupusresearch.org/home.html Alliance for Lupus Research] *[http://www.lupusuk.org.uk The Lupus UK Site] *[http://www.lupus.org/webmodules/webarticlesnet/templates/new_healthpatient.aspx?articleid=133&zoneid=27/Patient Resources for Lupus] {{Diseases of the skin and subcutaneous tissue}} {{Diseases of the musculoskeletal system and connective tissue}} [[Category:Arthritis]] [[Category:Diseases involving the fasciae]] [[Category:Rheumatology]] [[Category:Nephrology]] [[Category:Autoimmune diseases]] [[Category:Diseases]] [[bg:Лупус]] [[ca:Lupus eritematós sistèmic]] [[da:Systemisk Lupus Erythematosus]] [[de:Lupus erythematodes]] [[el:Συστηματικός ερυθηματώδης λύκος]] [[es:Lupus eritematoso sistémico]] [[fa:لوپوس منتشر]] [[fr:Lupus érythémateux disséminé]] [[id:Lupus eritematosus sistemik]] [[it:Lupus eritematoso sistemico]] [[he:זאבת]] [[la:Lupus erythematodes]] [[ms:Lupus eritematosus sistemik]] [[nl:Lupus erythematodes]] [[ja:全身性エリテマトーデス]] [[pl:Toczeń rumieniowaty układowy]] [[pt:Lupus eritematoso sistêmico]] [[ru:Системная красная волчанка]] [[simple:Lupus erythematosus]] [[fi:SLE]] [[sv:Systemisk lupus erythematosus]] [[th:โรคลูปัส]] [[tr:Sistemik lupus eritematozus]] [[zh:紅斑性狼瘡]]