Lucan · Conditions

Systemic lupus erythematosus

Australian guidance: eTG Rheumatology — SLE

1. Definition and epidemiology

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune connective tissue disease characterised by systemic inflammation, autoantibody production, and immune complex deposition causing end-organ injury. It affects approximately 1 in 1,000 Australians, with a striking female predominance of roughly 9:1 and peak onset in women of childbearing age (15 to 45 years). Aboriginal and Torres Strait Islander Australians, and those of Asian, African, and Hispanic ancestry, carry a higher disease burden and a more severe phenotype than European Australians.

2. Pathophysiology

The central defect in SLE is a failure to clear apoptotic cell debris, leading to persistent exposure of nuclear antigens (double-stranded DNA, histones, ribonucleoproteins) to the adaptive immune system. Defects in complement components, particularly C1q and C4, impair immune complex clearance via the classical pathway and allow antigen accumulation. Autoreactive B cells, with T follicular helper cell assistance, generate pathogenic autoantibodies including anti-dsDNA and anti-Smith (anti-Sm). These circulating immune complexes deposit in small vessels, renal glomeruli, synovium, and dermal capillaries, activating complement (generating C3a and C5a anaphylatoxins) and recruiting neutrophils and monocytes. Neutrophil extracellular traps release further nuclear material, amplifying the inflammatory loop. Overproduction of type I interferon (IFN-alpha) by plasmacytoid dendritic cells, stimulated by nucleic acid ligands via Toll-like receptors (TLR7 and TLR9), constitutes the interferon signature present in the majority of patients and is a key therapeutic target. End-organ injury results from both immune complex-mediated inflammation and ischaemia secondary to vasculitis and thrombosis, the latter especially prominent in antiphospholipid antibody-positive disease.

3. Clinical presentation and diagnostic criteria

SLE is the prototypical autoimmune disease and a diagnostic great mimicker. Constitutional symptoms (fatigue, fever, weight loss) are almost universal and may precede organ-specific features by years. Shared features with other inflammatory connective tissue diseases include arthralgias, myalgias, photosensitivity, fatigue, Raynaud phenomenon, and sicca symptoms, as described in eTG Rheumatology (inflammatory-ctd-sle.md). SLE-specific features include a photosensitive malar (butterfly) rash sparing the nasolabial folds, discoid lupus lesions, painless oral ulcers, and non-scarring alopecia. Non-erosive arthritis or arthralgia occurs in over 90% of patients and is often the presenting complaint. Lupus nephritis affects 50 to 60% and is the strongest predictor of long-term morbidity. Neuropsychiatric SLE, serositis (pleuritis, pericarditis), haematological cytopenias (haemolytic anaemia, lymphopaenia, thrombocytopaenia), and secondary antiphospholipid syndrome are important manifestations.

Diagnosis uses the 2019 EULAR and ACR classification criteria: a weighted scoring system across seven domain categories (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, and renal), anchored by a mandatory entry criterion of a positive ANA titre of at least 1:80. A score of 10 or more classifies SLE. The diagnosis is largely clinical; investigations support but do not replace clinical assessment, consistent with eTG guidance.

4. Investigations and AU-specific cutoffs

All investigations below should be ordered only when clinical features are highly suggestive of SLE; eTG explicitly cautions against requesting ANA or specific autoantibodies without high pretest probability (inflammatory-ctd-sle.md, ARA Choosing Wisely Recommendations 2 and 5).

Antinuclear antibody (ANA): screening immunoassay; titre and staining pattern both reported. Titres below 1:160 are common in healthy individuals and likely non-significant. Titres above 1:160 are considered abnormal; titres of 1:160 to 1:320 are nonspecific; titres of 1:640 or more are high. A negative ANA (or titre below 1:160) makes SLE unlikely and does not warrant further specific autoantibody testing unless clinical suspicion remains high (eTG; ARA Choosing Wisely Recommendation 5). ANA titre does not correlate with disease activity and does not require serial monitoring.

Specific autoantibodies (order only if ANA positive and clinical features suggestive): - Anti-dsDNA: present in 60% of people with SLE; found in only 2 to 5% of the general population and rarely in other inflammatory connective tissue diseases (eTG Table 12.21). Titres correlate with disease activity and nephritis risk. - Anti-Smith (Sm): present in 10 to 50% of people with SLE; highly specific, rare in general population and other connective tissue diseases (eTG Table 12.21). - Anti-Ro (SS-A): present in 40% of people with SLE; also common in Sjogren syndrome (eTG Table 12.21). Relevant in pregnancy (neonatal lupus, foetal heart block risk). - Anti-La (SS-B): present in 15% of people with SLE (eTG Table 12.21). - Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin IgG/IgM, anti-beta-2-glycoprotein I IgG/IgM): present in 30 to 50% of people with SLE (eTG Table 12.21, NB3). Confirm persistence at 12 weeks before applying antiphospholipid syndrome criteria.

Monitoring investigations: - Full blood count: haemolytic anaemia (Coombs-positive), lymphopaenia, thrombocytopaenia. - Complement C3 and C4: low levels indicate active immune complex-mediated disease; monitor serially alongside anti-dsDNA. - Urine microscopy, protein:creatinine ratio (PCR), and eGFR at every visit. Urine PCR above 50 mg/mmol warrants nephrology review and consideration of renal biopsy. Active urinary sediment (red cell casts, dysmorphic red cells) indicates glomerulonephritis. - Lipid profile, blood glucose, and blood pressure: cardiovascular risk is markedly elevated; accelerated atherosclerosis is independent of corticosteroid use.

5. Management

Management is guided by disease activity, organ involvement, and damage accrual. eTG Rheumatology recommends urgent referral to a rheumatologist for any suspected SLE diagnosis; rheumatologists have fast-track triage systems and direct GP contact is encouraged (inflammatory-ctd-sle.md).

Hydroxychloroquine (HCQ) is recommended for all patients with SLE unless contraindicated. Consistent with eTG dosing guidance (up to 5 mg/kg actual body weight daily), HCQ reduces flare frequency, prevents irreversible organ damage, lowers cardiovascular risk, and decreases mortality. Baseline ophthalmological review is required before initiation.

Corticosteroids are the mainstay of acute flare management. For patients with inflammatory connective tissue disease requiring corticosteroids for systemic or severe articular symptoms, eTG recommends prednisolone (or prednisone) 5 to 15 mg orally daily; higher doses are rarely necessary and carry greater adverse effect burden. The treatment goal is to minimise long-term corticosteroid exposure given contributions to damage accrual (osteoporosis, avascular necrosis, cataracts, infection). Co-prescribe calcium and vitamin D supplementation and consider bisphosphonate therapy when corticosteroids are anticipated to exceed three months.

Immunosuppressants are added for moderate to severe disease or as steroid-sparing agents. For difficult-to-control arthralgias and arthritis in inflammatory connective tissue disease, eTG supports hydroxychloroquine and methotrexate (10 to 25 mg orally or subcutaneously once weekly, with folic acid 5 to 10 mg weekly on a separate day) as options (inflammatory-ctd-sle.md). For lupus nephritis, mycophenolate mofetil (MMF) and cyclophosphamide are first-line induction agents for Class III and IV nephritis.

Biologics: belimumab (anti-BLyS monoclonal antibody) is TGA-approved and PBS-listed for active, seropositive SLE inadequately controlled on standard therapy. Anifrolumab (anti-IFN receptor) is TGA-approved (2023) for moderate to severe SLE.

If general practitioners start an oral corticosteroid before specialist review, eTG advises using the lowest effective dose and ideally weaning to below 10 mg/day before rheumatology review, as corticosteroids can mask clinical signs.

6. Pharmacology and AU PBS notes

Hydroxychloroquine (Plaquenil): PBS listed for SLE. Maximum dose 5 mg/kg actual body weight per day. Baseline ophthalmology review required. Annual screening from year five of use (or earlier with renal or hepatic impairment, or cumulative dose above 1,000 g).

NSAIDs for arthralgias/arthritis (eTG dosing): celecoxib 100 to 200 mg orally daily in 1 to 2 divided doses; or naproxen 250 to 500 mg orally twice daily; or meloxicam 7.5 to 15 mg orally daily. Paracetamol 1 g orally 4 to 6-hourly (maximum 4 g daily) is first-line for mild to moderate pain given its favourable safety profile (inflammatory-ctd-sle.md).

Prednisolone: unrestricted PBS. Co-prescribe calcium 1,200 mg daily and vitamin D 1,000 IU daily. Add alendronate 70 mg weekly (PBS) when corticosteroids are expected to continue beyond three months.

Methotrexate: 10 to 25 mg orally or subcutaneously once weekly on one specified day, plus folic acid 5 to 10 mg weekly not on the same day (eTG dosing for inflammatory connective tissue disease arthritis, inflammatory-ctd-sle.md). PBS authority required.

Azathioprine: PBS authority for SLE maintenance. Screen for TPMT deficiency; low TPMT activity mandates dose reduction. Monitor full blood count and liver function tests.

Mycophenolate mofetil (CellCept and generics): PBS authority for lupus nephritis. Highly teratogenic; adequate contraception mandatory. Cease at least three months before planned conception.

Belimumab (Benlysta): PBS streamlined authority for active seropositive SLE (ANA-positive or anti-dsDNA-positive, SLEDAI score 8 or more, inadequate response to HCQ and at least one other immunosuppressant). Available as monthly IV infusion or weekly subcutaneous injection.

7. Complications and monitoring

Lupus nephritis: the single greatest determinant of long-term prognosis. Class III and IV proliferative nephritis carries the highest risk of progression to end-stage kidney disease. Six-monthly urine PCR and eGFR surveillance is recommended in all patients; nephrology review for new proteinuria above 50 mg/mmol or declining eGFR.

Antiphospholipid syndrome (APS): venous or arterial thrombosis and pregnancy morbidity in the context of persistent antiphospholipid antibodies (confirmed on two occasions at least 12 weeks apart). Long-term anticoagulation with warfarin (target INR 2 to 3 for venous APS; 3 to 4 for recurrent arterial APS) is the AU standard. Direct oral anticoagulants are not currently recommended for APS due to inferior efficacy, particularly in triple-positive patients.

Cardiovascular disease: risk is elevated five to tenfold above age-matched controls, driven by accelerated atherosclerosis and traditional risk factors amplified by corticosteroids. Annual cardiovascular risk factor assessment; statin therapy per AU lipid guidelines.

Infection: increased susceptibility from immune dysregulation and immunosuppressive therapy. Ensure all vaccines are up to date before initiating immunosuppression. Live attenuated vaccines are contraindicated once immunosuppressives are commenced.

Hydroxychloroquine retinopathy: a dose-dependent toxicity that is largely irreversible once established. Automated visual field testing and spectral domain optical coherence tomography (SD-OCT) are the preferred AU surveillance modalities. Annual review from year five (or from year one with risk factors).

Pregnancy complications: SLE increases risk of pre-eclampsia, preterm birth, intrauterine growth restriction, and neonatal lupus (anti-Ro/anti-La-mediated foetal heart block). HCQ is safe and recommended throughout pregnancy. Mycophenolate must be ceased at least three months before conception. Obstetric and rheumatology co-management is standard at AU tertiary centres. Disease should be quiescent for at least six months before conception is attempted.

Monitoring schedule (stable disease): full blood count, renal function, urine PCR, C3/C4, anti-dsDNA, and SLEDAI-2K score every 3 to 6 months; lipid profile, blood glucose, and blood pressure every 6 to 12 months; bone mineral density every two years on corticosteroids; ophthalmology annually from year five of HCQ use.

Fatigue: a common and difficult-to-manage feature of all inflammatory connective tissue diseases. Exclude other causes (infection, psychosocial factors, iron deficiency). Optimise lifestyle factors; general measures are discussed in eTG (inflammatory-ctd-sle.md).

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.