systemic lupus erythematosus

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]^[13]^[14]^[15]^[16]^[17]^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25]^[26]^[27]^[28]^[29]^[30]^[31]^[32]^[33]^[34]^[35]^[36]^[37]^[38]^[39]^[40]^[41]^[42]^[43]^[44]^[45]^[46]^[47]^[48]^[49]

Introduction

See criteria for SLE.

Etiology

genetic factors
hormonal factors
- 90% of patients with SLE are women
  - onset of puberty greatly increases risk in women^[7]
- 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]
- both males & females with SLE have increased hydroxylation estrone to 16-hydroxyestrone, a potent estrogen
- males with Klinefelter's syndrome are prone to develop SLE
environmental factors
- increased frequency of autoantibodies in laboratory workers who handle blood of patients with SLE
- pharmacologic agents can trigger SLE or SLE-like syndromes (see drug-induced lupus erythematosus)
- chronic sleep deprivation is associated with increased risk of SLE in women with stronger effects among women with body pain & depression^[49]

Epidemiology

see etiology (hormonal factors)
prevalence is USA is 1/2000
females > males (> 10-fold)
2-3 fold more common in non-whites

Pathology

autoantigen exposure thought to occur during apoptosis
immune complex-mediated injury:
- glomerulonephritis: dsDNA:anti-dsDNA complex most common
- hypocomplementemia
cell-specific antibodies
increase production of IFN-alpha & IFN-beta
end organ damage^[7]

Genetics

gain of function in TLR7 (X-linked) implicated in SLE^[47]
polymorphism of TLR5 is associated with resistance to SLE type 1
increased frequency of SLE & immunologic abnormalities in relatives of patients with SLE; especially high concordance in monozygotic twins
association of SLE with:
- complement C1, complement C2 & complement C4 deficiencies
- HLA-DR2 & DR3
- deletion of C4A gene in Caucasians
- susceptibility linked to CTLA4, RASGRP1, TNFSF4, PDCD1
increased incidence of SLE in certain ethnic groups
- African Americans
- Puerto Ricans
- Asians
- Polynesians
other implicated genes:
- SLC5A11, NAT2, CD180, TREX1, PTPN22
- BLK & C8orf13 (chromosome 8p23.1) ITGAM (CD11b) & ITGAX (CD11c) (chromosome 16p11.22)^[21]

Clinical manifestations

disease generally develops gradually over weeks to months
- polyarthralgias, fever, rash (most comon)
- fatigue &/or weight loss is also common^[7]
- Raynaud's phenomenon (1/3 of SLE patients)
- myalgia, arthralgia & fatigue alone insufficient for SLE workup^[7]
fluctuating course with exacerbations & remissions
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
arthritis/arthralgia
- 90% of SLE patients at some time during the disease
- large & small joint involvement^[7]
- polyarticular & symmetric
- arthralgia more common than arthritis; minimal or no joint swelling^[7]
- generally non-deforming, but when joint erosion does occur, it is usually secondary to tenosynovitis
- Jaccoud arthropathy (nonerosive)
  - reducible subluxation of digits
  - swan neck deformities
  - ulnar deviation
- spontaneous tendon rupture rare
  - patellar tendon
  - Achilles tendon
cardiac manifestations
- pericarditis
  - most common cardiac manifestation of SLE
  - rarely may progress to constrictive pericarditis
- coronary artery disease (CAD)
  - high incidence of CAD in SLE patients treated with glucocorticoids
- myocarditis, cardiomyopathy
- valvular disease with antiphospholipid antibody syndrome
  - mitral regurgitation, aortic regurgitation
  - non infectious endocarditis^[7]
pulmonary manifestations
- pleurisy (50-80%), parenchymal lung involvement uncommon
- pleural effusion
  - small to moderate in size
  - bilateral in 50%
- dyspnea
- cough
- hemoptysis (15%)
- pulmonary alveolar hemorrhage (10%; mortality is >50%)
- pulmonary embolism (relatively common)
- diffuse pulmonary fibrosis (very uncommon)
- pneumonitis (rare)
- diaphragmatic dysfunction with basilar atelectasis (resistant to treatment)
neurologic manifestations:
- headache (common)
- neuropsychiatric manifestations:
  - psychosis
  - anxiety, mood disorder (common)
  - confusion (delirium), cognitive impairment (common)
- grand mal seizures (20% of SLE patients)
- cerebrovascular disease, stroke, hemiplegia
- aseptic meningitis, encephalitis^[7]
- demyelinating disease, transverse myelitis
- movement disorder, chorea
- Guillain-Barre syndrome
- peripheral neuropathy
  - autonomic neuropathy
  - cranial neuropathy (13%)
  - plexopathy
  - mononeuropathy (11%)
  - mononeuritis multiplex (9%)
  - predilection for asymmetric & lower extremity involvement, especially peroneal & sural nerves^[28]
muscle & neuromuscular
- myalgias
- myasthenia gravis^[7]
renal manifestations
- occur in 50% of SLE patients
  - may occur in otherwise asymptomatic patients^[7]
- glomerulonephritis
- pitting edema from proteinuria
antiphospholipid antibody syndrome
- arterial thrombosis
- venous thrombosis
- recurrent fetal loss
- livedo reticularis
- valvular heart disease
Sjogren's syndrome (keratoconjunctivitis sicca)
lymphadenopathy
splenomegaly
serositis^[7]

Diagnostic criteria

see criteria for SLE

Laboratory

complete blood count (CBC)
- anemia:
  - microcytic or normocytic
    - normocytic anemia of chronic inflammation is common^[7]
  - direct antiglobulin test (Coomb's) [DAT] may suggest hemolytic anemia
    - autoimmune hemolytic anemia in 10% correlates with SLE activity^[7]
  - iron saturation, transferrin saturation
    - > 15%; pattern of anemia of chronic disease
    - < 9%; iron deficiency secondary to GI blood loss
- leukopenia & lymphopenia
- thrombocytopenia
  - may be secondary to antiplatelet antibodies
  - 1st manifestation of SLE may be immune thrombocytopenic purpura (ITP)
  - associated with antiphospholipid antibody syndrome
chemistry panel
- renal function studies (routine monitoring indicated)^[7]
  - serum creatinine, serum urea nitrogen
    - rising serum creatinine suggests lupus nephritis
urinalysis (routine monitoring indicated)^[7]
- urine protein, urine protein/creatinine, 24 hour urine protein
  - urine protein > 500 mg/24 hours (proteinuria)
    - suggests active lupus nephritis
- hematuria
- urine microscopy:
  - erythrocyte casts, granular casts (active urine sediment)
    - suggests active lupus nephritis
erythrocyte sedimentation rate (ESR) C-reactive protein in serum^[7]
autoantibodies (see autoantibodies in SLE)
- antinuclear antibodies (ANA) (> 95% ) (first test, screening)
  - not diagnostic of SLE, no correlation with SLE activity^[7]
  - four patterns
    - rim (dsDNA): correlates with renal disease
    - speckled associated with Smith antigen
    - homogeneous
    - nucleolar: sometimes associated with scleroderma
- 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]
- 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]
- 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]
- anti-SSA (30%) associated with:
  - neonatal lupus, photosensitvity, discoid lupus, Sjogren syndrome
- anti-SSB (20%) associated with:
  - Sjogren syndrome, neonatal lupus (< anti-SSA)
- antiribosomal P protein (15%)
  - associated with psychosis, depression, & lupus hepatitis
- rheumatoid factor is often positive
- anti-histone antibody
  - associated with drug-induced lupus
- PCNA < 10%
- direct antiglobulin test: + anti-IgG & anti-C3d (warm autoimmune hemolytic anemia)
- other autoantibodies:
  - TRIM68, RAB11FIP5, THOC4, ANXA11, SSRP1, XRCC5, XRCC6
complement: C3, C4, CH50:
- decreases associated with active disease (in absence of congenital complement deficiency), especially lupus nephritis
hypercoagulability studies
- PT/PTT: prolonged PTT, normal PT not corrected by addition of equal volume of normal plasma in mixing studies
- lupus anticoagulant:
  - antiphospholipid antibodies [40%]
  - associated hypercoagulability
  - 30% of SLE patients
hepatitis C virus serology with reflex hepatitis C virus RNA^[8]
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
genetic testing
- PTPN22 gene mutation
see ARUP consult^[13]

Diagnostic procedures

pulmonary function testing:
- generally shows restrictive pattern
renal biopsy for suspected lupus nephritis
- begin high dose glucocorticoid prior to biopsy
thoracentesis (pleural effusion)
- exudative fluid
- C3, C4, CH50 levels low in 80%
- LE cells may be found
- glucose is normal or high
bronchosopy, bronchoalveolar lavage & bronchoscopic biopsy for diffuse alveolar hemorrhage due to suspected pulmonary infection^[7]
electromyography & nerve conduction studies for patients with peripheral neuropathy^[7]

Radiology

chest X-ray
- discoid atelectasis in lower 2/3 of lung fields
- pleural effusion (common, bilateral in 50%)
- patchy & irregular areas of interstitial pneumonitis (15-45%)
- infiltrates most commonly due to infectious processes in lupus patients receiving immunosuppressive therapy
bone density to screen for osteoporosis, osteopenia
joints without erosions^[7]

Complications

infections are the most common cause of death
- lupus patients are particularly susceptible to infection with encapsulated organisms
- biomodal distribution of mortality
  - early, within the 1st year
  - late, complications of immunosuppressive therapy
lupus flares
- must distinguish from infection
- generally gradual in onset
cardiac complications
- 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]
- pericarditis (25-50%)
- myocarditis
- valvular heart disease
  - non-infective endocarditis (20-60%)
  - valvular regurgitation (<20%)^[7]
stroke
increased risk of malignancies
- relative risk 1.15
- lymphoma, lung cancer, hepatobiliary carcinoma^[7]
- use of immunosuppressive agents contributes to risk^[7]
osteonecrosis, especially when treated with glucocorticoids^[7]
- pain or limited range of motion of hip suggests osteonecrosis^[7]
vertebral fracture^[7]^[19]
pulmonary
- diffuse alveolar hemorrhage (rare, but potentially fatal)^[27]
- acute lupus pneumonitis^[7]
lupus anticoagulant
- venous thromboembolism, arterial thromboembolism
- miscarriage
- livedo reticularis
- cytopenias
- valvular heart disease (see above)
complications of pregnancy^[7]
- 2-5 fold risk for miscarriage, stillbirth & premature labor
- 8-fold risk for intrauterine growth retardation
- fetus of woman with anti-SSA/Ro Ab or anti-SSB/La Ab at risk for neonatal lupus syndrome (rash, congenital heart block)^[7]
factors adversely affecting survival of SLE patients
- infections, glomerulnephritis, myocarditis
- low socioeconomic status, male gender,
- age > 50 years at diagnosis^[7]
warm autoimmune hemolytic anemia^[7]
leukocytoclastic vasculitis (image)^[46]
severe thrombocytopenia^[45]
also see complications of lupus erythematosus

Differential diagnosis

infection
- subacute bacterial endocarditis
- HIV (false positive ELISA for HIV may occur with SLE)
- hepatitis C virus (HCV)^[8]
  - false positive ELISA for HCV (obtain PCR)
  - HCV may mimic SLE
malignancy: lymphoma
other connective tissue diseases
rosacea: ANA positive patient with facial rash that involves the nasolabial folds^[7]

* also see criteria for SLE

Management

pharmacologic agents

non-steroidal anti-inflammatory agents (NSAIDs)
- indications:
  - arthritis^[7]
  - serositis
- dosage: standard per NSAID
hydroxychloroquine sulfate (Plaquenil) 200-400 mg QD
- all patients with SLE (if tolerated)^[7]; safe during pregnancy^[7]
- benefit for rash, serositis, arthritis
- decreases frequency of disease flares
- benefit during the entire course of the disease including exacerbations & remissions^[11]
- reduces mortality
- annual routine ophthalmology exam^[7]
glucocorticoids
- indications:
  - arthritis uncontrolled by hydroxychloroquine or NSAIDs
  - serositis
  - hematologic complications
  - renal complications
  - CNS complications
  - safe in pregnancy
- prednisone:
  - arthritis or serositis
    - 10-20 mg/day for short period
  - hematologic, CNS or renal complications
    - 1 mg/kg/day
- taper to lowest effective dose
- initiate immunosuppressive agent simultaneously with glucocorticoid to achieve disease control & allow tapering of glucocorticoid
mycophenolate preferable to cylcophosphamide for SLE & lupus nephritis^[7]
azathioprine for moderate to severe SLE^[7]
- well tolerated in pregnancy, inactivated by placenta^[7]
cyclophosphamide (Cytoxan)
- indications:
  - hematologic complications
  - renal complications
    - diffuse proliferative glomerulonephritis
    - prevention of renal failure
  - CNS complications
- 0.5-1 gram/m2 body surface IV
  - q4-6 weeks for 6 months
  - then, quarterly for 2 years
- may be used in combination with prednisone
belimumab (Benlysta) add-on therapy for severe SLE in patients already on standard therapy^[12]
rituximab for refractory SLE may reduce glucocorticoid use^[35]
baricitinib may be of benefit^[37]
CAR T-Cell immunotherapy reversed refractory SLE in 5 young people (4 women, 1 man) >= 8 months^[48]

preventive medicine

screen for & treat osteoporosis
calcium & vitamin D for all patients
bisphosphonate for patients with osteoporosis & osteopenia
minimize cardiovascular risk factors
- atorvastatin 40 mg QD not effective^[14]
avoid estogen-progestin oral contraceptives in patients with severe or unstable SLE, antiphospholipid antibody, or history of thrombosis^[7]
contraception
- avoid estrogen-containing contraceptive in women with lupus anticoagulant due to risk of thrombosis^[7]
- use barrier methods, IUD (progestin-containing IUD ok)
vaccination
- influena virus vaccine
- pneumococcal vacccine: PCV13 followed by PPSV23 1 year later
- recombinant herpes virus vaccine (Shingrix) if > 50 years
vigilance for malignancy (see complications)

diet

control of hypertension:
- low sodium diet
- weight loss
control of hyperlipidemia:
- weight loss
- low fat, low cholesterol diet

patient education

avoid sunlight; use sunscreen SPF > 30, long-sleeved clothing, hat
immunization for influenza & pneumococcus
avoid pregnancy during active disease
- delay until lupus is inactive for 6 months
- 25-45% of lupus patients have exacerbation, usually 8 weeks after delivery
barrier contraception
- low dose estrogen if oral contraception is necessary
regular medical follow-up

Comparative biology

Enterococcus gallinarum has a causative role in a mouse model of systemic lupus erythematosus^[36]

More general terms

More specific terms

Additional terms

References

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↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307
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↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/18700175
↑ ^45.0 ^45.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23462431
↑ ^46.0 ^46.1 Yang L, Zeng YP Images in Dermatology. Cutaneous Vasculitis in Systemic Lupus Erythematosus. JAMA Dermatol. 2021;157(8):991 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34160552 https://jamanetwork.com/journals/jamadermatology/fullarticle/2781365
↑ ^47.0 ^47.1 ^47.2 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: https://www.ncbi.nlm.nih.gov/pubmed/35477763 PMCID: PMC9095492 Free PMC article https://www.nature.com/articles/s41586-022-04642-z
↑ ^48.0 ^48.1 Mackensen A et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022 Oct; 28:2124. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36109639 https://www.nature.com/articles/s41591-022-02017-5
↑ ^49.0 ^49.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36094865 https://onlinelibrary.wiley.com/doi/10.1002/acr.25017

Patient information

systemic lupus erythematosus patient information

Database

OMIM: https://mirror.omim.org/entry/152700
OMIM: https://mirror.omim.org/entry/134638
OMIM: https://mirror.omim.org/entry/610927
OMIM: https://mirror.omim.org/entry/601744

[ref1-1] Stedman's Medical Dictionary 24th ed, Williams & Wilkins, Baltimore, 1982

[ref2-2] Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39.

[ref3-3] OMIM #134638.0001

[ref4-4] Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 790-792

[ref5-5] 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: https://www.ncbi.nlm.nih.gov/pubmed/7755231

[ref6-6] Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 609-610, 787-88

[ref7-7] 7.00 ^7.01 ^7.02 ^7.03 ^7.04 ^7.05 ^7.06 ^7.07 ^7.08 ^7.09 ^7.10 ^7.11 ^7.12 ^7.13 ^7.14 ^7.15 ^7.16 ^7.17 ^7.18 ^7.19 ^7.20 ^7.21 ^7.22 ^7.23 ^7.24 ^7.25 ^7.26 ^7.27 ^7.28 ^7.29 ^7.30 ^7.31 ^7.32 ^7.33 ^7.34 ^7.35 ^7.36 ^7.37 ^7.38 ^7.39 ^7.40 ^7.41 ^7.42 ^7.43 ^7.44 ^7.45 ^7.46 ^7.47 ^7.48 ^7.49 ^7.50 ^7.51 ^7.52 ^7.53 ^7.54 ^7.55 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

[ref8-8] 8.0 ^8.1 ^8.2 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: https://www.ncbi.nlm.nih.gov/pubmed/11145039

[ref9-9] Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307

[ref10-10] Prescriber's Letter 14(12): 2007 Hydroxychloroquine (Plaquenil) and Systemic Lupus Erythrometosus Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=231201&pb=PRL (subscription needed) http://www.prescribersletter.com

[ref11-11] 11.0 ^11.1 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]. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19103632 <Internet> http://dx.doi.org/10.1136/ard.2008.101766

[ref12-12] 12.0 ^12.1 Prescriber's Letter 18(5): 2011 Management of Systemic Lupus Erythematosus Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270512&pb=PRL (subscription needed) http://www.prescribersletter.com

[ref13-13] 13.0 ^13.1 ARUP Consult: Systemic Lupus Erythematosus - SLE The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/systemic-lupus-erythematosus

[ref14-14] 14.0 ^14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21177297

[ref15-15] 15.0 ^15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/19833754

[ref16-16] 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: https://www.ncbi.nlm.nih.gov/pubmed/19591783

[ref17-17] D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17307106

[ref18-18] 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: https://www.ncbi.nlm.nih.gov/pubmed/19622996

[ref19-19] 19.0 ^19.1 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: https://www.ncbi.nlm.nih.gov/pubmed/19224131

[ref20-20] 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: https://www.ncbi.nlm.nih.gov/pubmed/20501526

[ref21-21] 21.0 ^21.1 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: https://www.ncbi.nlm.nih.gov/pubmed/18204098

[ref22-22] 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: https://www.ncbi.nlm.nih.gov/pubmed/1902614

[ref23-23] 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: https://www.ncbi.nlm.nih.gov/pubmed/19136143

[ref24-24] 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: https://www.ncbi.nlm.nih.gov/pubmed/20131238

[ref25-25] Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011 Dec 1;365(22):2110-21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22129255

[ref26-26] 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: https://www.ncbi.nlm.nih.gov/pubmed/22009248

[ref27-27] 27.0 ^27.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21558137

[ref28-28] 28.0 ^28.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21641018

[ref29-29] 29.0 ^29.1 ^29.2 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: https://www.ncbi.nlm.nih.gov/pubmed/23857662

[ref30-30] Barber C, Gold WL, Fortin PR Infections in the lupus patient: perspectives on prevention. Curr Opin Rheumatol. 2011 Jul;23(4):358-65 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21532484

[ref31-31] 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: https://www.ncbi.nlm.nih.gov/pubmed/22832823

[ref32-32] 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: https://www.ncbi.nlm.nih.gov/pubmed/9324032

[ref33-33] 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: https://www.ncbi.nlm.nih.gov/pubmed/18945994

[ref34-34] 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: https://www.ncbi.nlm.nih.gov/pubmed/23422269

[ref35-35] 35.0 ^35.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29216396

[ref36-36] 36.0 ^36.1 Rosenbaum JT, Silverman GT The Microbiome and Systemic Lupus Erythematosus. N Engl J Med 2018; 378:2236-2237. June 7, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29874543 https://www.nejm.org/doi/full/10.1056/NEJMcibr1804368

[ref37-37] 37.0 ^37.1 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

[ref38-38] Mittoo S, Fell CD. Pulmonary manifestations of systemic lupus erythematosus. Semin Respir Crit Care Med. 2014 Apr;35(2):249-54. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24668539

[ref39-39] 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: https://www.ncbi.nlm.nih.gov/pubmed/27639157

[ref40-40] Pisetsky DS. Anti-DNA antibodies--quintessential biomarkers of SLE. Nat Rev Rheumatol. 2016 Feb;12(2):102-10. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26581343

[ref41-41] Popescu A, Kao AH. Neuropsychiatric systemic lupus erythematosus. Curr Neuropharmacol. 2011 Sep;9(3):449-57. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22379459 Free PMC Article

[ref42-42] 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: https://www.ncbi.nlm.nih.gov/pubmed/27587201

[ref43-43] 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: https://www.ncbi.nlm.nih.gov/pubmed/25441491 Free Article

[ref44-44] 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: https://www.ncbi.nlm.nih.gov/pubmed/18700175

[ref45-45] 45.0 ^45.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23462431

[ref46-46] 46.0 ^46.1 Yang L, Zeng YP Images in Dermatology. Cutaneous Vasculitis in Systemic Lupus Erythematosus. JAMA Dermatol. 2021;157(8):991 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34160552 https://jamanetwork.com/journals/jamadermatology/fullarticle/2781365

[ref47-47] 47.0 ^47.1 ^47.2 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: https://www.ncbi.nlm.nih.gov/pubmed/35477763 PMCID: PMC9095492 Free PMC article https://www.nature.com/articles/s41586-022-04642-z

[ref48-48] 48.0 ^48.1 Mackensen A et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022 Oct; 28:2124. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36109639 https://www.nature.com/articles/s41591-022-02017-5

[ref49-49] 49.0 ^49.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36094865 https://onlinelibrary.wiley.com/doi/10.1002/acr.25017

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systemic lupus erythematosus

Contents

Introduction

Etiology

Epidemiology

Pathology

Genetics

Clinical manifestations

Diagnostic criteria

Laboratory

Diagnostic procedures

Radiology

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Differential diagnosis

Management

pharmacologic agents

preventive medicine

diet

patient education

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Additional terms

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systemic lupus erythematosus

Introduction

Etiology

Epidemiology

Pathology

Genetics

Clinical manifestations

Diagnostic criteria

Laboratory

Diagnostic procedures

Radiology

Complications

Differential diagnosis

Management

pharmacologic agents

preventive medicine

diet

patient education

Comparative biology

More general terms

More specific terms

Additional terms

References

Patient information

Database

Navigation menu

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