Rheumatology & Nephrology & Internal Medicine & Family Medicine
Systemic lupus erythematosus (SLE)
Systemic lupus erythematosus (SLE - formerly known as systemic lupus erythematosus or SLE) is a chronic, relapsing-remitting systemic autoimmune disease characterized by the production of autoantibodies directed against specific nuclear constituents (double-stranded DNA + histones + ribonucleoproteins) and by the deposition of immune complexes in the target organs - kidneys + joints + skin + serous membranes + CNS + hematopoiesis. It is a heterogeneous disease that can affect virtually any organ. The prevalence is 30-150 per 100,000 people, depending on the population, with a clear female predominance (F/H ratio of 9:1 in childbearing age) and incidence peaks between the ages of 15 and 45. Black, Asian and Hispanic populations are more severely and frequently affected than white populations. SLE is associated with increased mortality - mainly due to severe relapses (lupus nephritis + neurological damage + DIC) and complications of immunosuppressive treatments (opportunistic infections), as well as excess cardiovascular mortality due to atherosclerosis accelerated by chronic inflammation. Diagnosis is based on the new EULAR/ACR 2019 criteria (Aringer 2019 - Arthritis and Rheumatology) - replacing the ACR 1997 criteria - which require a positive ANA (titer ≥1:80) as a mandatory entry criterion, followed by the accumulation of a weighted score of clinical and biological criteria ≥10 points across 7 domains. Hydroxychloroquine (HCQ) is the mainstay of treatment - prescribed to almost all lupus patients regardless of stage of activity, it reduces flare-ups, mortality and cardiovascular risk.
Pathophysiology, diagnostic criteria, and organ damage
- Pathophysiology and Immunological Basis of SLE Central immunological deregulation in SLE: loss of tolerance to nuclear autoantigens → production of IgG autoantibodies (ANA + anti-double-stranded DNA + anti-Sm + anti-SSA/Ro + anti-SSB/La + anti-U1 snRNP + antiribosomal P + antiphospholipid) → formation of immune complexes (IC) → deposition in target organs (renal glomeruli + joints + skin + vessels + CNS) → complement activation (C3 + C4 + CH50 decreased during flares) → inflammation → tissue damage → activation of type I interferon pathway (IFN-α ++) → IFN signature → biomarker and therapeutic target (anifrolumab - anti-IFNαR) + NETose (NETosis) : release of extracellular neutrophil traps (NETs) → source of autoantigens → amplification of autoimmune response → central pathogenic role → autoantibodies and their clinical significance: ANA (antinuclear antibodies): screening test → meaning. 97 % for LES → very sensitive + not very specific (positive in many autoimmune diseases + in 5-10 % of the general population) + anti-double-stranded DNA (anti-dsDNA): very specific for LES (>90 %) → correlates with disease activity and lupus nephritis → high titre = risk of flare → useful for follow-up + anti-Sm (anti-Smith): very specific for LES (95-99 %) → but not very sensitive (25-30 %) + anti-SSA (Ro): risk of neonatal lupus + congenital BAV in the fetus → MANDATORY screening in early pregnancy + antiphospholipids (aPL): risk of thrombosis + abortions (SAPL) → anti-Ro/SSA + anti-La/SSB + anti-U1snRNP: LES + Sharp syndrome (MCTD); EULAR/ACR 2019 criteria for LES classification (Aringer 2019): mandatory entry criterion: ANA ≥1:80 on HEp-2 (at least once) → then weighted score on 7 domains: constitutional (unexplained fever = 2 pts) + cutaneous (malar rash = 4 pts + discoid lupus = 4 pts + capillary fall = 2 pts + oral ulcers = 2 pts + photosensitivity = 4 pts) + articular (arthritis ≥2 joints = 6 pts) + neurological (psychosis + convulsions = 5 pts) + serous (effusion + pericarditis = 5 pts) + hematological (thrombocytopenia <100 × 10⁹l = "4" pts + leucopénie <4 3 anémiehémolytique ="4" pts) rénal (protéinurie>500 mg/24h = 4 pts + casts = 4 pts + lupus nephritis biopsy class III/IV = 8 pts) + biological (low C3 OR C4 = 3 pts + low C3 AND C4 = 4 pts + positive anti-dsDNA = 6 pts + positive anti-Sm = 6 pts + positive aPL = 2 pts) → score ≥10 = SLE classification (excluding alternative causes)
- Organ damage and disease activity: SLEDAI-2K (SLE Disease Activity Index): score 0-105 → summarizes disease activity in 10 organs → score >6 = active disease → score >12 = very active disease → used for therapeutic decisions + clinically significant organ involvement: skin involvement : malar rash (butterfly rash - erythema of the cheeks + butterfly wing nose - classic but present in only 50 % of cases) + discoid lupus + photosensitivity + alopecia + painless oral ulcers + joint involvement: polyarthralgia/polyarthritis (90 % of LES) + non-erosive + symmetrical + renal involvement (lupus nephritis): the most severe complication → 50 % of LES + ISN/RPS or Oxford classifications - class III (focal) + class IV (diffuse - most severe) + class V (membranous) + renal biopsy essential if proteinuria >500 mg/24h + or hematuria + or cylinders → neuropsychiatric involvement (NPSLE): psychosis + convulsions + neuropathy + stroke → Hanly 2019 - Arthritis Care Research + hematological involvement: autoimmune cytopenias (hemolytic anemia + autoimmune thrombocytopenia + leukopenia) → Coombs direct often positive + cardiovascular involvement: pericarditis + myocarditis + Libman-Sacks endocarditis + accelerated atherosclerosis → cardiovascular risk × 5-10 compared with general population + pulmonary involvement: pleuritis + lupus pneumonitis + pulmonary arterial hypertension + alveolar hemorrhage (emergency)
Treatment of SLE according to affected organs and severity
| Treatment / damage | Data, protocols and results | Key studies and recommendations |
|---|---|---|
| Background treatment — hydroxychloroquine and immunosuppressants Hydroxychloroquine Plaquenil — ophthalmologic surveillance — azathioprine — mycophenolate — methotrexate — belimumab anifrolumab — flare — prednisone — corticosteroid sparing — LLDAS goal — photoprotection |
Background treatment for SLE - therapeutic pillars: hydroxychloroquine (HCQ - Plaquenil): universal treatment prescribed to ALL patients with SLE regardless of stage → dosage: 200-400 mg/d (target <5 mg/kg actual body weight/d to minimize retinopathy) → demonstrated benefits: reduced flare-ups + reduced mortality (Ruiz-Irastorza 2010 - Lupus) + reduced cardiovascular risk + reduced risk of thrombosis (anti-aPL) + prevention of neonatal lupus if anti-Ro/SSA positive + onset of action: 2-3 months → ophthalmological monitoring: baseline + annually after 5 years → AAO 2016 (OCT + visual field) → EULAR 2023 maximum recommendation <5 mg/kg/d → azathioprine (AZA) 1-3 mg/kg/d : maintenance treatment of moderate forms → lupus renal class III-IV in maintenance + skin + joint + hematological involvement + thiopurine methyltransferase (TPMT) activity → adapt dose → mycophenolate mofetil (MMF) 2-3 g/d: 1st line for lupus nephritis (induction + maintenance) → contraindicated in pregnancy → methotrexate 7.5-20 mg/sem: arthritis + skin involvement → good tolerance → associated folic acid + belimumab (Benlysta - anti-BLyS/BAFF): first biologic approved for LES → IV 10 mg/kg × D0 + D14 + D28 then monthly → or SC 200 mg/week → BLISS-52 (Navarra 2011 - Lancet) + BLISS-76 (Furie 2011 - Arthritis and Rheumatism): belimumab vs placebo + standard therapy → reduction in flares by 50-60 % → BLISS-LN 2020 - NEJM: belimumab + MMF in lupus nephritis → improved renal responses → reduction in renal flares → Health Canada 2011 + anifrolumab (Saphnelo - anti-IFNαR): type I IFN receptor inhibitor → TULIP-2 2021 - NEJM: anifrolumab vs placebo → reduction in BICLA responder rate → especially for cutaneous + articular + hematological forms + corticoids: prednisone 0.5-1 mg/kg/d for flares → gradually reduce → objective: maintenance dose <7.5 mg/d (<5 mg/d preferable) → cumulative corticosteroid dose is an independent factor in irreversible damage → corticosteroid sparing with immunosuppressants ++ → therapeutic goal: LLDAS (Lupus Low Disease Activity State): SLEDAI-2K ≤4 + prednisone ≤7.5 mg/d + no new relapses → or remission (SLEDAI-2K = 0) | Navarra 2011 — Lancet (BLISS-52): belimumab + SLE → flare reduction 50–60% % → reference + Furie 2011 — Arthritis and Rheumatism (BLISS-76): belimumab + SLE → confirmed results + Morand 2020 — NEJM (TULIP-2): anifrolumab + SLE → BICLA reduction + especially cutaneous/joint → Ruiz-Irastorza 2010 — Lupus: HCQ + SLE → mortality reduction + flares → reference HCQ + BLISS-LN 2020 — NEJM: belimumab + MMF + lupus nephritis → EULAR 2023 guidelines SLE: treatment → universal HCQ + therapeutic targets + CCS (Canadian Rheumatology Association) + INESSS Quebec: HCQ + AZA + MMF + belimumab + anifrolumab → reimbursed by criteria + RAMQ: Plaquenil + azathioprine + MMF + belimumab → reimbursed |
| Lupus Nephritis - Diagnosis, Classification, and Treatment Renal biopsy — class III IV V — mycophenolate induction — cyclophosphamide Euro Lupus — rituximab — voclosporin — obinutuzumab — proteinuria — hematuria — casts — eGFR — renal outcome — EULAR 2023 |
Lupus nephritis (LN) - the most serious renal complication of SLE: indicators of renal involvement requiring biopsy: proteinuria >500 mg/24h (or protein/creatinine ratio >500 mg/g) + and/or hematuria with erythrocyte cylinders + and/or unexplained increase in creatinine → renal biopsy: gold standard → ISN/RPS 2004 classification (revised): class I: minimal mesangial → class II: mesangial + class III: focal (50 % of glomeruli) - most severe → class V: membranous → class VI: advanced sclerosis (>90 % of sclerosis) + treatment of class III-IV NL (most frequent + most severe): induction phase (goal: complete or partial remission in 6-12 months): mycophenolate mofetil (MMF) 2-3 g/d + prednisone 0.5-1 mg/kg/d: 1st-line treatment (EULAR 2023) + Call 2009 - JASN: MMF vs cyclophosphamide IV → non-inferiority → preferred because less gonadal toxicity → cyclophosphamide IV (Euro Lupus protocol: 500 mg × 6 doses every 2 weeks): alternative if MMF insufficient → or countries without MMF available + Houssiau 2002 - Arthritis and Rheumatism (Euro Lupus Nephritis Trial): low-dose cyclophosphamide non-inferior to high-dose + voclosporin (Lupkynis) + MMF + prednisone : AURORA trial (Rovin 2021 - Lancet): voclosporin + MMF → superior to MMF alone for complete renal remission → Health Canada 2022 → add belimumab if persistent → maintenance phase: MMF 1.5-2 g/d (or AZA) × 3-5 years minimum → renal objective (EULAR 2023): complete remission = proteinuria <500 mg/24h + stable renal function (eGFR ≥60 % of baseline) → universal HCQ even in NL → rituximab (anti-CD20) : refractory forms → obinutuzumab: trials in progress (NOBILITY trial - favorable) → NL class V: MMF + prednisone → or cyclosporine + associated SAPL treatment: if aPL positive → HCQ ± low-dose aspirin → if thrombosis → AVKs | 2009 Appel - JASN: MMF vs IV cyclophosphamide + NL → non-inferiority → MMF preferred 2002 Houssiau - Arthritis and Rheumatism (Euro Lupus): low-dose cyclophosphamide → non-inferior 2021 Rovin - Lancet (AURORA trial): voclosporin + MMF → superior → complete renal remission → reference 2020 BLISS-LN - NEJM: belimumab + MMF + NL → positive results 2012 Bertsias - Annals of Rheumatic Diseases (EULAR guidelines NL) EULAR 2023 guidelines SLE + LN (Lupus Nephritis) Canadian Rheumatology Association: NL + biopsy + treatment INESSS Québec + RAMQ: MMF + cyclophosphamide + voclosporin + belimumab → reimbursed according to NL criteria Health Canada: voclosporin Lupkynis 2022 + obinutuzumab trials |
| LES and pregnancy, cardiovascular surveillance and complications Lupus pregnancy planning — HCQ pregnancy — anti-Ro/SSA congenital heart block — LMWH — obstetric APS — monthly monitoring — postpartum flare — accelerated cardiovascular risk — statins — SLEDAI monitoring — ANA anti-dsDNA follow-up |
LES and pregnancy - specific considerations: pregnancy planning: remission or low lupus activity ≥6 months before conception → reduced risk of relapse + obstetric complications + pre-conception workup: SLEDAI + anti-dsDNA + complement + aPL + anticardiolipin + anti-β2-GPI + anti-Ro/SSA + anti-La/SSB + creatinine + urinary workup + HCQ must be MAINTAINED during pregnancy (improves maternal + fetal prognosis - Clowse 2006 - Arthritis and Rheumatism) → avoid MMF + cyclophosphamide + methotrexate (teratogenic) → AZA acceptable → drugs compatible with pregnancy: HCQ + prednisone + AZA + LMWH + aspirin + anti-Ro/SSA positive: risk of congenital atrioventricular block (AVB) in the fetus (2-3 % if 1st child + 15-20 % if ATCD of congenital AVB) → fetal monitoring by fetal echocardiography from 16 to 26 SA → if AVB confirmed: dexamethasone (only corticosteroid passing placenta) → HCQ reduces risk of 65 % → Izmirly 2011 - Arthritis and Rheumatism → SAPL and pregnancy: LMWH + aspirin 75-100 mg/d throughout pregnancy → monthly monitoring during pregnancy: SLEDAI + complement + anti-dsDNA + CBC + proteinuria + creatinine + liver workup → risk of lupus flare: 15-30 % during pregnancy or postpartum → postpartum: high risk of flare → maintain treatments → breastfeeding: compatible HCQ + compatible low-dose prednisone + compatible AZA; accelerated cardiovascular risk in LES: atherosclerosis is accelerated by chronic inflammation + corticosteroids + kidney damage + SAPL → risk of MI × 5-10 + risk of stroke × 2-5 → CV risk management: statins if usual indication + or if moderate-high CV risk on calculators → good BP management (target <130/80 mmHg) + HCQ reduces CV risk → control of modifiable risk factors: tobacco + diabetes + BP + dyslipidemia + SLEDAI and biological monitoring of activity: SLEDAI-2K every 3-6 months + anti-dsDNA + C3 + C4 + CBC + creatinine + proteinuria → lower corticosteroids if possible | Clowse 2006 — Arthritis and Rheumatism: HCQ + pregnancy SLE → improved maternal + fetal prognosis → reference + Izmirly 2011 — Arthritis and Rheumatism: HCQ + anti-Ro + congenital heart block → 65% reduction % → Petri 2013 — Arthritis and Rheumatism: SLE + pregnancy + flares + risks → EULAR 2017 recommendations on SLE pregnancy + EULAR 2023 guidelines SLE + Canadian Rheumatology Association (CRA): SLE + pregnancy + Bertsias 2012 + CRA guidelines pregnancy + lupus + Gordon 2010 — Rheumatology: SLE + cardiovascular risk + Manzi 1997 — American Journal of Epidemiology: SLE + MI × 50 women 35–44 years + INESSS Quebec + RAMQ: HCQ + AZA + prednisone + LMWH + statins reimbursed + AAO 2016: HCQ ophthalmologic surveillance |
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Hydroxychloroquine is the universal pillar of lupus treatment—it should be prescribed to almost all lupus patients and maintained during pregnancy: The new EULAR/ACR 2019 criteria require ANA ≥1:80 as a mandatory entry criterion, then a weighted score ≥10 points across 7 domains. Class IV (diffuse) lupus nephritis is the most severe renal complication and requires kidney biopsy for classification — MMF is now the first-line induction therapy. Positive anti-Ro/SSA antibodies mandate fetal surveillance by echocardiography between 16 and 26 weeks of gestation to detect congenital atrioventricular block.
Situations requiring urgent rheumatological or internal medicine consultation
Patient with known lupus + new or worsened proteinuria >500 mg/24h + hematuria with casts + progressive increase in creatinine → lupus nephritis → urgent renal biopsy (within 2 weeks) → SLEDAI + complement + anti-dsDNA → induction with MMF + prednisone → or Euro Lupus cyclophosphamide if MMF is insufficient → urgent rheumatology + nephrology consultation.
Seizures, new onset psychosis, neurological deficit, or confusion, without another obvious cause. → NPSLE (neuropsychiatric lupus) → Emergency brain MRI + LP → SLEDAI + complement + anti-dsDNA + aPL → intensive immunosuppressive treatment (IV methylprednisolone) + anticoagulation if aPL positive → hospitalization.
Pregnant woman with known lupus + fever + worsening proteinuria + hypertension + edema + thrombocytopenia → differentiate lupus flare vs preeclampsia (can coexist) → complement + anti-dsDNA (low = lupus flare) + LDH + AST (high = HELLP or preeclampsia) → urgent obstetrics + rheumatology consultation → hospitalization.
Systemic lupus erythematosus + acute dyspnea + hypoxemia + bilateral alveolar opacities + hemoptysis → Lupus-related alveolar hemorrhage → Life-threatening emergency → Bronchoalveolar lavage + bronchoscopy → IV methylprednisolone 1 g for 3 days → IV cyclophosphamide → Intensive care unit hospitalization.
Consult at Clinique Omicron
Clinique Omicron physicians assess signs suggestive of lupus (malar rash + arthralgia + cytopenias + proteinuria + positive ANA), prescribe initial workup (ANA + anti-dsDNA + anti-Sm + antiphospholipids + complement + CBC + renal panel + urinalysis), initiate and monitor hydroxychloroquine (ophthalmology + eGFR), track SLEDAI and biological activity every 3-6 months, recognize rheumatologic emergencies (lupus nephritis + NPSLE + alveolar hemorrhage), and coordinate with rheumatologists, nephrologists, and obstetricians for lupus pregnancies. Consultations are available at multiple service points across Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not replace the advice of a doctor, rheumatologist, or nephrologist. Lupus is a complex systemic disease that requires regular multidisciplinary monitoring. Any kidney, neurological, or hematological flare-up must be evaluated as an emergency by a specialist.
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