Systemic lupus erythematosus (SLE)

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Understanding this condition

What it is

SLE is a chronic multisystem autoimmune disease driven by loss of self-tolerance, autoantibody formation, and immune-complex deposition, producing inflammation across mucocutaneous, musculoskeletal, renal, haematologic, serosal, cardiopulmonary, and neuropsychiatric domains. Genetic, epigenetic, hormonal, and environmental factors contribute to pathogenesis.^[1]

Symptoms

Manifestations span constitutional symptoms, mucocutaneous disease (malar and photosensitive rashes, oral ulcers, alopecia), inflammatory arthritis (joint involvement in up to 95 percent of patients), serositis, cytopenias, renal disease, and neuropsychiatric syndromes. A useful framing distinguishes type 1 (inflammatory) manifestations that respond to immunosuppression from type 2 symptoms (fatigue, widespread pain, mood disturbance, cognitive dysfunction) that often dominate patient-reported outcomes but respond less to immunosuppression.^[1]

Who gets it

US prevalence is about 72.8 per 100,000, with a strong predilection for reproductive-aged women and worse prognosis in people of Black, Hispanic, American Indian or Alaska Native, and Asian ancestry. Socioeconomic and structural factors contribute to disparities in outcomes.^[1]

How it is diagnosed

Diagnosis is clinical, integrating history, examination, serology (ANA and specific autoantibodies), and laboratory and organ assessment, after excluding mimics. The 2025 ACR treatment guideline explicitly does not address diagnosis. For research and consistency, SLE is classified with the 2019 EULAR/ACR classification criteria (see the classification note below); these are classification, not diagnostic, criteria.^{[1, 3]}

What to expect over time

With modern therapy most patients can attain remission or low disease activity. Long-term prognosis is driven by organ damage accrual (from disease and from treatment, particularly glucocorticoids), by lupus nephritis (which occurs in close to half of patients and can progress to end-stage kidney disease in 10 to 22 percent), and by accelerated cardiovascular risk. Reducing damage accrual while minimising treatment toxicity is central to long-term care.^{[1, 2]}

Living with and treating it

Goals of treatment

The goal is optimal disease control, defined as remission or a low disease activity state, to reduce morbidity and mortality while minimising treatment-related toxicity. DORIS remission and LLDAS are the validated target states. Patient priorities, life stage, and values should shape goals through shared decision-making, and routine treat-to-target as a formal strategy remains a future goal without randomized-trial support in SLE.^{[1, 3, 4]}

Treatment options

Hydroxychloroquine is the backbone for nearly all patients. Glucocorticoids provide rapid control and are minimised over time. For ongoing activity or to enable steroid tapering, conventional immunosuppressives (methotrexate, mycophenolic acid analogs, or azathioprine) and/or biologics (belimumab or anifrolumab) are added, without a fixed hierarchy and guided by organ involvement and patient preference. Intravenous cyclophosphamide is reserved for organ- or life-threatening disease and anti-CD20 therapy (rituximab or obinutuzumab) for refractory disease. Organ-specific recommendations apply where one system predominates.^{[1, 3]}

Tests and monitoring

Assess disease activity regularly, including at any change in clinical status or medications, using a validated instrument (SELENA-SLEDAI or SLEDAI-2K, or BILAG) with a physician global assessment; assess damage at least annually with the SLICC/ACR Damage Index. Screen for proteinuria at least every 6 to 12 months, or with extra-renal flares. Hydroxychloroquine retinopathy screening is performed at baseline and then annually, no later than 5 years after starting.^{[1, 2]}

Flares

Flares range from mild to organ- or life-threatening. Severity and the organ system involved guide the intensity and choice of therapy; for ongoing activity in any organ system refractory to initial therapy, escalation of therapy is strongly recommended. Life- or organ-threatening flares are treated urgently with pulse or high-dose glucocorticoids plus immunosuppressive therapy.^[1]

Living well

Non-pharmacologic measures include photoprotection (sunscreen with SPF 70 or higher for chemical and 50 or higher for physical blockers, plus sun-avoidance measures), smoking cessation, regular exercise, vaccination, and attention to bone, cardiovascular, and mental health. Pregnancy should be planned during stable low activity on pregnancy-compatible medications; this is addressed in the reproductive-health guideline and the pregnancy guides.^{[1, 3]}

Related conditions and risks

SLE and its therapies carry increased risk of infection, cardiovascular disease (SLE is a cardiovascular risk-enhancing factor), osteoporosis and avascular necrosis, and malignancy, with an enhanced cervical-cancer screening protocol. Antiphospholipid antibody assessment should be part of comorbidity screening given its impact on disease manifestations and thrombotic risk. Screening and management follow the referenced comorbidity guidance; the guideline frames these as suggestions drawn from outside sources rather than formal SLE treatment recommendations.^[1]

What to expect at your appointment

A first or follow-up SLE visit covers a symptom and functional history, examination, and activity and organ assessment (bloods, urinalysis with protein quantification). Patient-panel work highlights that people with lupus prioritise shared decision-making, discussion of all options with their side effects and costs, compassionate and non-judgmental communication, and a team-based approach; incorporating these priorities improves adherence and outcomes. Agree an individualised plan and monitoring schedule.^{[1, 4]}

Additive weighted criteria (apply when the ANA entry criterion is met) · classify if score 10 or more of a possible 51, with at least one clinical criterion

Within each domain only the highest-weighted criterion counts, so the achievable maximum is 51 rather than the sum of every row. A criterion counts only where SLE is the most likely explanation, and antinuclear-antibody-negative patients cannot be classified by these criteria. The criteria are for research and trial entry and are explicitly not intended to diagnose an individual.

Treatment ladder

1. 1

   Foundation for everyone

   Hydroxychloroquine for nearly all patients unless contraindicated, continued indefinitely, at 5 mg/kg/day or less to limit retinal toxicity (short courses of 5 to 6.5 mg/kg/day may be used at initiation or to regain control). Add photoprotection and comorbidity and cardiovascular risk management as part of the foundation.

   Hydroxychloroquine is strongly recommended by the 2025 ACR guideline and is a 1b/A EULAR 2023 recommendation.

2. 2

   Control the flare, then lower the steroid

   Glucocorticoids for rapid control: pulse intravenous methylprednisolone (250 to 1000 mg for 1 to 3 days) then oral taper for organ- or life-threatening flares, and in stable controlled disease taper prednisone to 5 mg/day or less (ideally to zero) within 6 months. Use glucocorticoids as a bridge, not maintenance.

   The taper-to-5 mg/day-or-less recommendation is strong (2025 ACR); the pulse-methylprednisolone recommendation for severe flares is conditional.

3. 3

   Add steroid-sparing therapy for ongoing activity

   For ongoing activity or inability to taper steroids, add a conventional immunosuppressive (methotrexate, mycophenolic acid analogs, or azathioprine) and/or a biologic (belimumab or anifrolumab), without a fixed hierarchy and guided by organ involvement and patient preference. Organ-specific recommendations apply where one system predominates.

   EULAR 2023 grades methotrexate 1b/B, mycophenolate 2a/B, azathioprine 2b/C, and belimumab and anifrolumab 1a/A; anifrolumab is used the same way but does not yet have a guide here.

4. 4

   Severe or refractory organ disease

   For organ- or life-threatening disease, intravenous cyclophosphamide should be considered; for refractory disease, rituximab or another anti-CD20 agent may be considered. Plasma exchange and/or IVIG are options as adjuncts for life-threatening manifestations. Escalation is strongly recommended for refractory organ activity.

   EULAR 2023 grades cyclophosphamide for organ- or life-threatening disease 2b/C and rituximab for refractory disease 2b/C.

Guideline recommendations

Key points

Medication guides

Plain-language guides to the medicines used for this condition. Each has a patient and a clinician view.

• Hydroxychloroquine
• Glucocorticoids
• Methotrexate
• Mycophenolate
• Azathioprine
• Belimumab
• Anifrolumab
• Cyclophosphamide
• Rituximab

Key numbers

• Lupus nephritis occurs in close to half of people with SLE; 10 to 22 percent of those with LN progress to end-stage kidney disease.^[2]
• Joint involvement occurs in up to 95 percent of people with SLE, with permanent joint damage in about 11.7 percent.^[1]

References

1. Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2025. doi:10.1002/acr.25690 https://doi.org/10.1002/acr.25690
2. Sammaritano LR, Askanase A, Bermas BL, et al. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis Care Res (Hoboken). 2025;77(9):1045-1065. doi:10.1002/acr.25528 https://doi.org/10.1002/acr.25528
3. Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83(1):15-29. doi:10.1136/ard-2023-224762 https://doi.org/10.1136/ard-2023-224762
4. Garg S, Hartel I, Sammaritano LR, et al. A Qualitative Analysis of Patient Perspectives and Preferences in Lupus Management to Guide Lupus Guidelines Development. Arthritis Care Res (Hoboken). 2025. doi:10.1002/acr.25693 https://doi.org/10.1002/acr.25693
5. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019;78(9):1151 to 1159. doi:10.1136/annrheumdis-2018-214819 https://doi.org/10.1136/annrheumdis-2018-214819