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systemic lupus erythematosus

See criteria for SLE. Etiology: 1) genetic factors 2) hormonal factors a) 90% of patients with SLE are women - onset of puberty greatly increases risk in women [7] b) in young adults, SLE is 10-13 times more common in females than in males - gain of function in TLR7 (X-linked) implicated in SLE [47] c) both males & females with SLE have increased hydroxylation estrone to 16-hydroxyestrone, a potent estrogen d) males with Klinefelter's syndrome are prone to develop SLE 3) environmental factors a) increased frequency of autoantibodies in laboratory workers who handle blood of patients with SLE b) pharmacologic agents can trigger SLE or SLE-like syndromes (see drug-induced lupus erythematosus) c) chronic sleep deprivation is associated with increased risk of SLE in women with stronger effects among women with body pain & depression [49] d) long-term exposure to air pollutants (PM2.5, PM10, NO2, & NOx) may increase risk of developing systemic lupus erythematosus (RR=1.1-1.3) [51] Epidemiology: 1) see etiology (hormonal factors) 2) prevalence is USA is 1/2000 3) females > males (> 10-fold) 4) 2-3 fold more common in non-whites Pathology: 1) autoantigen exposure thought to occur during apoptosi - expansion of T follicular helper & T peripheral helper cells produce high levels of the B-cell chemoattractant CXCL13 - aryl hydrocarbon receptor (AHR) is a potent negative regulator of CXCL13 production by human CD4+ T-cells - AHR coordinates with JUN to prevent CXCL13+ T-cell differentiation & promote IL-22+ T-helper cells (Th22) - IFN-alpha is a pathogenic driver of SLE - IFN-alpha opposes AHR & JUN to promote T-cell production of CXCL13 - CXCL13+ T-cells oppose TH22 cells with AHR, JUN & IFN-alpha as key regulators [50] 2) immune complex-mediated injury: a) glomerulonephritis: dsDNA:anti-dsDNA complex most common b) hypocomplementemia 3) cell-specific antibodies a) erythrocyte, leukocytes & platelets b) neurons c) endothelial cells 4) increase production of IFN-alpha & IFN-beta 5) end organ damage [7] Genetics: 1) gain of function in TLR7 (X-linked) implicated in SLE [47] 2) polymorphism of TLR5 is associated with resistance to SLE type 1 3) increased frequency of SLE & immunologic abnormalities in relatives of patients with SLE; especially high concordance in monozygotic twins 4) association of SLE with: a) complement C1, complement C2 & complement C4 deficiencies b) HLA-DR2 & DR3 c) deletion of C4A gene in Caucasians d) susceptibility linked to CTLA4, RASGRP1, TNFSF4, PDCD1 5) increased incidence of SLE in certain ethnic groups a) African Americans b) Puerto Ricans c) Asians d) Polynesians 6) other implicated genes: - SLC5A11, NAT2, CD180, TREX1, PTPN22 - BLK & C8orf13 (chromosome 8p23.1) ITGAM (CD11b) & ITGAX (CD11c) (chromosome 16p11.22) [21] Clinical manifestations: 1) disease generally develops gradually over weeks to months a) polyarthralgias, fever, rash (most comon) b) fatigue &/or weight loss is also common [7] c) Raynaud's phenomenon (1/3 of SLE patients) c) myalgia, arthralgia & fatigue alone insufficient for SLE workup [7] 2) fluctuating course with exacerbations & remissions 3) dermatologic manifestations - malar rash (butterfly rash) - erythema & edema over cheeks, chin & bridge of nose [7] - spares nasolabial folds - photosensitive rash [7] - discoid lupus - face, neck, scalp & external ears - central scarring with atrophy - subacute cutaneous SLE - upper torso - association with HLA DR3 & Ro antibody - non scarring - telangiectasias common - lupus panniculitis - squamous cell carcinoma may arise with cutaneous lesions of SLE - oral ulcers: often painful, generally painless [7] - alopecia - generally diffuse & non scarring - may be first sign of disease 4) arthritis/arthralgia a) 90% of SLE patients at some time during the disease b) large & small joint involvement [7] c) polyarticular & symmetric d) arthralgia more common than arthritis; minimal or no joint swelling [7] e) generally non-deforming, but when joint erosion does occur, it is usually secondary to tenosynovitis f) Jaccoud arthropathy (nonerosive) 1] reducible subluxation of digits 2] swan neck deformities 3] ulnar deviation g) spontaneous tendon rupture rare 1] patellar tendon 2] Achilles tendon 5) cardiac manifestations a) pericarditis 1] most common cardiac manifestation of SLE 2] rarely may progress to constrictive pericarditis b) coronary artery disease (CAD) - high incidence of CAD in SLE patients treated with glucocorticoids c) myocarditis, cardiomyopathy d) valvular disease with antiphospholipid antibody syndrome - mitral regurgitation, aortic regurgitation - non infectious endocarditis [7] 6) pulmonary manifestations a) pleurisy (50-80%), parenchymal lung involvement uncommon b) pleural effusion 1] small to moderate in size 2] bilateral in 50% c) dyspnea d) cough e) hemoptysis (15%) f) pulmonary alveolar hemorrhage (10%; mortality is >50%) g) pulmonary embolism (relatively common) h) diffuse pulmonary fibrosis (very uncommon) i) pneumonitis (rare) j) diaphragmatic dysfunction with basilar atelectasis (resistant to treatment) 7) neurologic manifestations: a) headache (common) b) neuropsychiatric manifestations: 1] psychosis 2] anxiety, mood disorder (common) 3] confusion (delirium), cognitive impairment (common) c) grand mal seizures (20% of SLE patients) d) cerebrovascular disease, stroke, hemiplegia e) aseptic meningitis, encephalitis [7] f) demyelinating disease, transverse myelitis g) movement disorder, chorea h) Guillain-Barre syndrome i) peripheral neuropathy 1] autonomic neuropathy 2] cranial neuropathy (13%) 3] plexopathy 4] mononeuropathy (11%) 5] mononeuritis multiplex (9%) 6] predilection for asymmetric & lower extremity involvement, especially peroneal & sural nerves [28] 8) muscle & neuromuscular - myalgias - myasthenia gravis [7] 9) renal manifestations a) occur in 50% of SLE patients - may occur in otherwise asymptomatic patients [7] b) glomerulonephritis c) pitting edema from proteinuria 10) antiphospholipid antibody syndrome a) arterial thrombosis b) venous thrombosis c) recurrent fetal loss d) livedo reticularis e) valvular heart disease 11) Sjogren's syndrome (keratoconjunctivitis sicca) 12) lymphadenopathy 13) splenomegaly 14) serositis [7] Diagnostic criteria: - see criteria for SLE Laboratory: 1) complete blood count (CBC) a) anemia: 1] microcytic or normocytic - normocytic anemia of chronic inflammation is common [7] 2] direct antiglobulin test (Coomb's) [DAT] may suggest hemolytic anemia - autoimmune hemolytic anemia in 10% correlates with SLE activity [7] 3] iron saturation, transferrin saturation - > 15%; pattern of anemia of chronic disease - < 9%; iron deficiency secondary to GI blood loss b) leukopenia & lymphopenia c) thrombocytopenia 1] may be secondary to antiplatelet antibodies 2] 1st manifestation of SLE may be immune thrombocytopenic purpura (ITP) 3] associated with antiphospholipid antibody syndrome 2) chemistry panel - renal function studies (routine monitoring indicated) [7] - serum creatinine, serum urea nitrogen - rising serum creatinine suggests lupus nephritis 3) urinalysis (routine monitoring indicated) [7] a) urine protein, urine protein/creatinine, 24 hour urine protein - urine protein > 500 mg/24 hours (proteinuria) - suggests active lupus nephritis b) hematuria c) urine microscopy: - erythrocyte casts, granular casts (active urine sediment) - suggests active lupus nephritis 4) erythrocyte sedimentation rate (ESR) C-reactive protein in serum [7] 5) autoantibodies (see autoantibodies in SLE) a) antinuclear antibodies (ANA) (> 95% ) (first test, screening) 1] not diagnostic of SLE, no correlation with SLE activity [7] 2] four patterns a] rim (dsDNA): correlates with renal disease b] speckled associated with Smith antigen c] homogeneous d] nucleolar: sometimes associated with scleroderma b) anti-double-stranded DNA (50-60%) - > 95% specificity for SLE, 60% sensitivity for SLE [7] - increases most closely correlated with disease activity [7,29] - correlated with renal disease (glomerulonephritis) - useful for following disease activity of SLE, especially renal disease [7,29] c) anti Sm antibody (30%) - 99% specificity for SLE, 30% sensitivity for SLE [7] - associated with glomerulonephritis, CNS disease - antibody levels do not correlate with disease activity [7] d) anti-U1 ribonucleoprotein (anti-U1 RNP) (35%) - 35-46% sensitivity for SLE) [7] - associated with Raynaud's phenomenon, esophageal dysmotility, myositis - found in mixed connective tissue disease (MCTD) in high titer [7] e) anti-SSA (30%) associated with: - neonatal lupus, photosensitvity, discoid lupus, Sjogren syndrome f) anti-SSB (20%) associated with: - Sjogren syndrome, neonatal lupus (< anti-SSA) g) antiribosomal P protein (15%) - associated with psychosis, depression, & lupus hepatitis h) rheumatoid factor is often positive i) anti-histone antibody - associated with drug-induced lupus j) PCNA < 10% k) direct antiglobulin test: + anti-IgG & anti-C3d (warm autoimmune hemolytic anemia) l) other autoantibodies: - TRIM68, RAB11FIP5, THOC4, ANXA11, SSRP1, XRCC5, XRCC6 6) complement: C3, C4, CH50: - decreases associated with active disease (in absence of congenital complement deficiency), especially lupus nephritis 7) hypercoagulability studies a) PT/PTT: prolonged PTT, normal PT not corrected by addition of equal volume of normal plasma in mixing studies b) lupus anticoagulant: 1] antiphospholipid antibodies [40%] 2] associated hypercoagulability 3] 30% of SLE patients 8) hepatitis C virus serology with reflex hepatitis C virus RNA [8] 9) monitoring of disease activity & response to therapy [7] - CBC, ESR, anti-dsDNA in serum (see autoantibodies above) - complement C3 in serum, complement C4 in serum - urine protein/creatinine 10) genetic testing - PTPN22 gene mutation 11) see ARUP consult [13] Special laboratory: 1) pulmonary function testing: - generally shows restrictive pattern 2) renal biopsy for suspected lupus nephritis - begin high dose glucocorticoid prior to biopsy 3) thoracentesis (pleural effusion) a) exudative fluid b) C3, C4, CH50 levels low in 80% c) LE cells may be found d) glucose is normal or high 4) bronchosopy, bronchoalveolar lavage & bronchoscopic biopsy for diffuse alveolar hemorrhage due to suspected pulmonary infection [7] 5) electromyography & nerve conduction studies for patients with peripheral neuropathy [7] Radiology: 1) chest X-ray a) discoid atelectasis in lower 2/3 of lung fields b) pleural effusion (common, bilateral in 50%) c) patchy & irregular areas of interstitial pneumonitis (15-45%) d) infiltrates most commonly due to infectious processes in lupus patients receiving immunosuppressive therapy 2) bone density to screen for osteoporosis, osteopenia 3) joints without erosions [7] Differential diagnosis: 1) infection a) subacute bacterial endocarditis b) HIV (false positive ELISA for HIV may occur with SLE) c) hepatitis C virus (HCV) [8] 1] false positive ELISA for HCV (obtain PCR) 2] HCV may mimic SLE 2) malignancy: lymphoma 3) other connective tissue diseases a) mixed connective tissue disease b) rheumatoid arthritis (RA) c) vasculitis 4) rosacea: ANA positive patient with facial rash that involves the nasolabial folds [7] * also see criteria for SLE Complications: 1) infections are the most common cause of death a) lupus patients are particularly susceptible to infection with encapsulated organisms b) biomodal distribution of mortality 1] early, within the 1st year 2] late, complications of immunosuppressive therapy 2) lupus flares a) must distinguish from infection b) generally gradual in onset 3) cardiac complications a) premature coronary artery disease [7,15] - ischemic heart disease is the most cause of death in elderly with SLE [7] - high lupus inflammation & prednisone > 20 mg/day are risk factors [7] b) pericarditis (25-50%) c) myocarditis d) valvular heart disease 1] non-infective endocarditis (20-60%) 2] valvular regurgitation (<20%) [7] 4) stroke 5) increased risk of malignancies a) relative risk 1.15 b) lymphoma, lung cancer, hepatobiliary carcinoma [7] c) use of immunosuppressive agents contributes to risk [7] 6) osteonecrosis, especially when treated with glucocorticoids [7] - pain or limited range of motion of hip suggests osteonecrosis [7] 7) vertebral fracture [7,19] 8) pulmonary - diffuse alveolar hemorrhage (rare, but potentially fatal) [27] - acute lupus pneumonitis [7] 9) lupus anticoagulant - venous thromboembolism, arterial thromboembolism - miscarriage - livedo reticularis - cytopenias - valvular heart disease (see above) 10) complications of pregnancy [7] a) 2-5 fold risk for miscarriage, stillbirth & premature labor b) 8-fold risk for intrauterine growth retardation c) fetus of woman with anti-SSA/Ro Ab or anti-SSB/La Ab at risk for neonatal lupus syndrome (rash, congenital heart block) [7] 11) factors adversely affecting survival of SLE patients - infections, glomerulnephritis, myocarditis - low socioeconomic status, male gender, - age > 50 years at diagnosis [7] 12) warm autoimmune hemolytic anemia [7] 13) leukocytoclastic vasculitis (image) [46] 14) severe thrombocytopenia [45] 15) also see complications of lupus erythematosus Management: === pharmacologic agents === 1) non-steroidal anti-inflammatory agents (NSAIDs) a) indications: 1] arthritis [7] 2] serositis b) dosage: standard per NSAID 2) hydroxychloroquine sulfate (Plaquenil) 200-400 mg QD a) all patients with SLE (if tolerated) [7]; safe during pregnancy [7] b) benefit for rash, serositis, arthritis c) decreases frequency of disease flares d) benefit during the entire course of the disease including exacerbations & remissions [11] e) reduces mortality f) annual routine ophthalmology exam [7] 3) glucocorticoids a) indications: 1] arthritis uncontrolled by hydroxychloroquine or NSAIDs 2] serositis 3] hematologic complications 4] renal complications 5] CNS complications 6] safe in pregnancy b) prednisone: 1] arthritis or serositis - 10-20 mg/day for short period 2] hematologic, CNS or renal complications - 1 mg/kg/day c) taper to lowest effective dose d) initiate immunosuppressive agent simultaneously with glucocorticoid to achieve disease control & allow tapering of glucocorticoid 4) mycophenolate preferable to cylcophosphamide for SLE & lupus nephritis [7] 5) azathioprine for moderate to severe SLE [7] - well tolerated in pregnancy, inactivated by placenta [7] 6) cyclophosphamide (Cytoxan) a) indications: 1] hematologic complications 2] renal complications a] diffuse proliferative glomerulonephritis b] prevention of renal failure 3] CNS complications b) 0.5-1 gram/m2 body surface IV 1] q4-6 weeks for 6 months 2] then, quarterly for 2 years c) may be used in combination with prednisone 7) belimumab (Benlysta) add-on therapy for severe SLE in patients already on standard therapy [12] 8) rituximab for refractory SLE may reduce glucocorticoid use [35] 9) baricitinib may be of benefit [37] 10) CAR T-Cell immunotherapy reversed refractory SLE in 5 young people (4 women, 1 man) >= 8 months [48] === preventive medicine === 1) screen for & treat osteoporosis 2) calcium & vitamin D for all patients 3) bisphosphonate for patients with osteoporosis & osteopenia 4) minimize cardiovascular risk factors - atorvastatin 40 mg QD not effective [14] 5) avoid estogen-progestin oral contraceptives in patients with severe or unstable SLE, antiphospholipid antibody, or history of thrombosis [7] 6) contraception a) avoid estrogen-containing contraceptive in women with lupus anticoagulant due to risk of thrombosis [7] b) use barrier methods, IUD (progestin-containing IUD ok) 7) vaccination - influena virus vaccine - pneumococcal vacccine: PCV13 followed by PPSV23 1 year later - recombinant herpes virus vaccine (Shingrix) if > 50 years 8) vigilance for malignancy (see complications) === diet === 1) control of hypertension: a) low sodium diet b) weight loss 2) control of hyperlipidemia: a) weight loss b) low fat, low cholesterol diet === patient education === 1) avoid sunlight; use sunscreen SPF > 30, long-sleeved clothing, hat 2) immunization for influenza & pneumococcus 3) avoid pregnancy during active disease a) delay until lupus is inactive for 6 months b) 25-45% of lupus patients have exacerbation, usually 8 weeks after delivery 4) barrier contraception - low dose estrogen if oral contraception is necessary 5) regular medical follow-up Comparative biology: - Enterococcus gallinarum has a causative role in a mouse model of systemic lupus erythematosus [36]

Interactions

disease interactions

Related

autoantibodies in systemic lupus erythmatosus (SLE) complications of lupus erythematosus diagnostic criteria for systemic lupus erythematosus (SLE) LE cell lupus anticoagulant

Specific

cutaneous lupus erythematosus drug-induced lupus erythematosus lupus erythematosus in pregnancy lupus nephritis lupus pneumonitis neonatal lupus erythematosus systemic lupus erythematosus in the elderly

General

autoimmune disease connective tissue disease; soft tissue disease

References

  1. Stedman's Medical Dictionary 24th ed, Williams & Wilkins, Baltimore, 1982
  2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39.
  3. OMIM #134638.0001
  4. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 790-792
  5. Boumpas DT et al Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med 122:940-50, 1995 PMID: 7755231
  6. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 609-610, 787-88
  7. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  8. Journal Watch 21(3):24, 2001 Ramos-Casals et al Hepatitis C virus infection mimicking systemic lupus erythematosus: study of hepatitis C virus infection in a series of 134 Spanish patients with systemic lupus erythematosus. Arthritis Rheum 43:2801, 2000 PMID: 11145039
  9. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307
  10. Prescriber's Letter 14(12): 2007 Hydroxychloroquine (Plaquenil) and Systemic Lupus Erythrometosus Detail-Document#: 231201 (subscription needed) http://www.prescribersletter.com
  11. Ruiz-Irastorza G et al Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: A systematic review. Ann Rheum Dis 2009 Jun 4; [e-pub ahead of print]. PMID: 19103632 http://dx.doi.org/10.1136/ard.2008.101766
  12. Prescriber's Letter 18(5): 2011 Management of Systemic Lupus Erythematosus Detail-Document#: 270512 (subscription needed) http://www.prescribersletter.com
  13. ARUP Consult: Systemic Lupus Erythematosus - SLE The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/systemic-lupus-erythematosus
  14. Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS. Lupus Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis. 2011 May;70(5):760-5 PMID: 21177297
  15. Goldberg RJ, Urowitz MB, Ibanez D, Nikpour M, Gladman DD. Risk factors for development of coronary artery disease in women with systemic lupus erythematosus. J Rheumatol. 2009 Nov;36(11):2454-61. PMID: 19833754
  16. Bernatsky S, Ramsey-Goldman R, Clarke AE. Malignancy in systemic lupus erythematosus: what have we learned? Best Pract Res Clin Rheumatol. 2009 Aug;23(4):539-47 PMID: 19591783
  17. D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96. PMID: 17307106
  18. Culwell KR, Curtis KM, del Carmen Cravioto M. Safety of contraceptive method use among women with systemic lupus erythematosus: a systematic review. Obstet Gynecol. 2009 Aug;114(2 Pt 1):341-53 PMID: 19622996
  19. Mendoza-Pinto C et al Risk factors of vertebral fractures in women with systemic lupus erythematosus. Clin Rheumatol. 2009 May;28(5):579-85 PMID: 19224131
  20. Gronhagen CM, Gunnarsson I, Svenungsson E, Nyberg F. Cutaneous manifestations and serological findings in 260 patients with systemic lupus erythematosus. Lupus. 2010 Sep;19(10):1187-94. PMID: 20501526
  21. Hom G, Graham RR, Modrek B et al Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med. 2008 Feb 28;358(9):900-9 PMID: 18204098
  22. Ippolito A, Petri M. An update on mortality in systemic lupus erythematosus. Clin Exp Rheumatol. 2008 Sep-Oct;26(5 Suppl 51):S72-9. PMID: 1902614
  23. Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010 Feb;39(4):257-68 PMID: 19136143
  24. Shinjo SK, Bonfa E, Wojdyla D, Borba EF et al Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort. Arthritis Rheum. 2010 Mar;62(3):855-62 PMID: 20131238
  25. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011 Dec 1;365(22):2110-21 PMID: 22129255
  26. Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol. 2011 Oct 18;7(12):718-29. PMID: 22009248
  27. Martinez-Martinez MU, Abud-Mendoza C. Predictors of mortality in diffuse alveolar haemorrhage associated with systemic lupus erythematosus. Lupus. 2011 May;20(6):568-74 PMID: 21558137
  28. Florica B, Aghdassi E, Su J et al Peripheral neuropathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum. 2011 Oct;41(2):203-11 PMID: 21641018
  29. Andrejevic S, Jeremic I, Sefik-Bukilica M et al Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity. Clin Rheumatol. 2013 Nov;32(11):1619-26 PMID: 23857662
  30. Barber C, Gold WL, Fortin PR Infections in the lupus patient: perspectives on prevention. Curr Opin Rheumatol. 2011 Jul;23(4):358-65 PMID: 21532484
  31. Elkon KB, Wiedeman A. Type I IFN system in the development and manifestations of SLE. Curr Opin Rheumatol. 2012 Sep;24(5):499-505 PMID: 22832823
  32. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725. PMID: 9324032
  33. Wu H, Birmingham DJ, Rovin B D-dimer level and the risk for thrombosis in systemic lupus erythematosus. Clin J Am Soc Nephrol. 2008 Nov;3(6):1628-36 PMID: 18945994
  34. Schoenfeld SR, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum. 2013 Aug;43(1):77-95 PMID: 23422269
  35. Walsh N. A Role for Rituximab in Lupus? Half of refractory patients responded in 6 months. MedPage Today. March 08, 2018 https://www.medpagetoday.com/rheumatology/lupus/71618 - McCarthy EM, Sutton E, Nesbit S et al Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: Results from the British Isles lupus assessment group biologics register. Rheumatology (Oxford). 2018 Mar 1;57(3):470-479. PMID: 29216396
  36. Rosenbaum JT, Silverman GT The Microbiome and Systemic Lupus Erythematosus. N Engl J Med 2018; 378:2236-2237. June 7, 2018 PMID: 29874543 https://www.nejm.org/doi/full/10.1056/NEJMcibr1804368
  37. Walsh N EULAR: Baricitinib Shows Promise in SLE. Significant clinical benefits with JAK inhibition in active lupus. MedPage Today. June 14, 2018 https://www.medpagetoday.com/meetingcoverage/eular/73500 - Wallace D, et al Baricitinib in systemic lupus erythematosus: results from a phase 2, randomized, double-blind, placebo-controlled study. European Congress of Rheumatology (EULAR) 2018; abstract OP0019
  38. Mittoo S, Fell CD. Pulmonary manifestations of systemic lupus erythematosus. Semin Respir Crit Care Med. 2014 Apr;35(2):249-54. Review. PMID: 24668539
  39. Vivero F, Gonzalez-Echavarri C, Ruiz-Estevez B et al Prevalence and predictors of valvular heart disease in patients with systemic lupus erythematosus. Autoimmun Rev. 2016 Dec;15(12):1134-1140. Review. PMID: 27639157
  40. Pisetsky DS. Anti-DNA antibodies--quintessential biomarkers of SLE. Nat Rev Rheumatol. 2016 Feb;12(2):102-10. Review. PMID: 26581343
  41. Popescu A, Kao AH. Neuropsychiatric systemic lupus erythematosus. Curr Neuropharmacol. 2011 Sep;9(3):449-57. PMID: 22379459 Free PMC Article
  42. Garcia A, De Sanctis JB. A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus. Curr Pharm Des. 2016;22(41):6306-6312. Review. PMID: 27587201
  43. Gontero RP, Bedoya ME, Benavente E, Roverano SG, Paira SO. Osteonecrosis in systemic lupus erythematosus. Reumatol Clin. 2015 May-Jun;11(3):151-5. PMID: 25441491 Free Article
  44. NEJM Knowledge+ Question of the Week. April 23, 2019 https://knowledgeplus.nejm.org/question-of-week/713/ - Conti F, Rezai S, Valesini G. Vaccination and autoimmune rheumatic diseases. Autoimmun Rev 2008 Aug 14; 8:124 PMID: 18700175
  45. Newman K, Owlia MB, El-Hemaidi I, Akhtari M. Management of immune cytopenias in patients with systemic lupus erythematosus - Old and new. Autoimmun Rev 2013 Mar 7; 12:784. PMID: 23462431
  46. Yang L, Zeng YP Images in Dermatology. Cutaneous Vasculitis in Systemic Lupus Erythematosus. JAMA Dermatol. 2021;157(8):991 PMID: 34160552 https://jamanetwork.com/journals/jamadermatology/fullarticle/2781365
  47. Brown GJ, Canete PF, Vinuesa CG et al TLR7 gain-of-function genetic variation causes human lupus. Nature 2022. 605:349-356 Apr 27 PMID: 35477763 PMCID: PMC9095492 Free PMC article https://www.nature.com/articles/s41586-022-04642-z
  48. Mackensen A et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022 Oct; 28:2124. PMID: 36109639 https://www.nature.com/articles/s41591-022-02017-5
  49. Choi, MY, Malspeis, S, Sparks, JA, Cui, J, Yoshida, K and Costenbader, KH. Association of sleep deprivation and the risk of developing systemic lupus erythematosus among women. Arthritis Care Res. September 12, 2022. PMID: 36094865 https://onlinelibrary.wiley.com/doi/10.1002/acr.25017
  50. Law C, Wacleche VS, Cao Y et al Interferon subverts an AHR-UN axis to promote CXCL13+ T cells in lupus. Nature. 2024 Jul 10. doi: 10.1038/s41586-024-07627-2 PMID: 38987586 https://www.nature.com/articles/s41586-024-07627-2
  51. Xing M, Ma Y, Cui F et al Air Pollution, Genetic Susceptibility, and Risk of Incident Systemic Lupus Erythematosus: A Prospective Cohort Study. Arthritis Rheumatol. 2024 Jul 10. PMID: 38982844 https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42929

Databases & Figures

OMIM correlations Diseases Associated with Inhibition of Apoptosis