Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks the body’s own tissues, causing inflammation and sometimes lasting organ damage. It can affect the skin, joints, kidneys, circulating blood cells, heart, lungs, and nervous system. Its course varies considerably: periods of increased disease activity, called flares, may alternate with periods of remission or lower activity. (niams.nih.gov)
Causes and biological mechanisms
SLE has no single established cause. Genetic susceptibility, environmental exposures, hormonal influences, and abnormalities of immune regulation contribute to its development. Most cases involve multiple genetic variants rather than a simple inheritance pattern. Having an affected relative increases susceptibility but does not mean that the disease will necessarily develop. Sunlight, certain infections, smoking, and some medicines can contribute to disease onset or activity in susceptible individuals. (niams.nih.gov)
The disease involves autoimmunity directed against components of the body’s own cells. Many patients produce autoantibodies that recognize nuclear material, including DNA and associated proteins. Autoantibodies and the immune complexes they form participate in tissue injury, particularly in the kidneys. Altered clearance of damaged or dead cells can expose cellular material to immune responses; interferon signaling and other immune pathways also contribute to the disease. These mechanisms interact rather than forming a single pathway that explains every patient’s manifestations. (niams.nih.gov)
Occurrence
SLE can occur at any age, including childhood, but most often develops between ages 15 and 45. Women are affected approximately nine times more often than men. In the United States, disease frequency differs among population groups, with higher occurrence reported in African American, Asian American, and Hispanic populations than in non-Hispanic White populations. (niams.nih.gov)
Clinical manifestations
Manifestations differ between individuals and can change over time. General symptoms include fatigue, fever, malaise, and weight changes. The extent of visible skin disease does not by itself describe the full range of organs involved. (niams.nih.gov)
Major manifestations include:
- Skin and mucous membranes: photosensitive eruptions, hair loss, and mouth or nasal ulcers. A characteristic malar, or butterfly-shaped, rash crosses the cheeks and bridge of the nose, but is not present in every patient.
- Joints: pain, swelling, and stiffness, often involving the hands, wrists, or knees.
- Blood: anemia, reduced white blood cell counts, or reduced platelet counts.
- Heart and lungs: inflammation of the lining around the heart or lungs, sometimes producing chest pain or fluid accumulation.
- Nervous system: seizures, cognitive or behavioral changes, and other neurological manifestations.
- Blood vessels: increased clotting risk in some patients, particularly in association with antiphospholipid antibodies. (medlineplus.gov)
Kidney involvement
Lupus nephritis is kidney inflammation caused by SLE and is a major form of organ involvement. Findings can include protein or blood in the urine, swelling, high blood pressure, and impaired kidney function. Kidney disease may progress to kidney failure. Evaluation uses urine testing, blood tests of kidney function, and, when indicated, a kidney biopsy to characterize the injury and inform treatment. (niddk.nih.gov)
Diagnosis and classification
Diagnosis depends on the combination of clinical history, examination, laboratory findings, and exclusion of alternative explanations. No single test establishes SLE. Symptoms may develop at different times, making the overall pattern more informative than an isolated finding. (niams.nih.gov)
Antinuclear antibody (ANA) testing is sensitive for SLE: almost all affected people have a positive result. However, ANA positivity also occurs in healthy people and does not, by itself, establish the diagnosis. Additional investigations may include anti-double-stranded DNA and anti-Smith antibodies, antiphospholipid antibodies, blood cell counts, complement components, kidney function tests, and urinalysis. Skin or kidney biopsy may provide further evidence. (niams.nih.gov)
The 2019 EULAR/ACR classification criteria were developed to identify relatively consistent groups of patients for research, not to replace clinical diagnosis. They require ANA positivity at least once as an entry criterion, followed by weighted clinical and immunological findings. Classification requires at least one clinical criterion and a total of at least 10 points. Only the highest-scoring finding within each domain counts, and findings are included only when no more likely explanation exists. Failure to meet classification criteria does not automatically exclude a clinical diagnosis. (pubmed.ncbi.nlm.nih.gov)
Treatment and its limitations
Treatment is directed at controlling disease activity, preventing flares and organ damage, and limiting treatment toxicity. The medicines used depend on the manifestations and severity of disease; there is no established cure. (niams.nih.gov)
Hydroxychloroquine, an antimalarial medicine with immunomodulatory effects, is a central component of treatment. Glucocorticoids suppress inflammation, while medicines such as methotrexate, azathioprine, mycophenolate, and cyclophosphamide are used for selected manifestations or more severe disease. Contemporary management guidelines emphasize minimizing prolonged glucocorticoid exposure and using other therapies to maintain disease control. (medlineplus.gov)
Targeted biological treatments include belimumab, which acts on B-cell activating factor, and anifrolumab, which blocks the type I interferon receptor. Kidney disease may require combinations of immunosuppressive medicines; belimumab and calcineurin inhibitors, including voclosporin, have roles in selected lupus nephritis regimens. These treatments are not interchangeable across all manifestations. (pubmed.ncbi.nlm.nih.gov)
The distinction between active inflammation, irreversible organ damage, and treatment adverse effects is important in assessing disease status. Long-term care also addresses infection risk, cardiovascular disease, bone health, and other complications. (niams.nih.gov)
Pregnancy and related forms of lupus
Pregnancy outcomes depend partly on disease activity, kidney involvement, hypertension, and antibody status. Antiphospholipid antibodies are associated with pregnancy loss and other complications, while anti-SSA/Ro and anti-SSB/La antibodies can cross the placenta and cause neonatal lupus, which may include skin disease or congenital heart block. Neonatal lupus is distinct from a newborn developing SLE. (niams.nih.gov)
The term lupus also encompasses related conditions. Cutaneous lupus erythematosus primarily affects the skin and can occur with or without systemic disease. Drug-induced lupus is associated with exposure to particular medicines and is distinguished from idiopathic SLE. These conditions share some features but are not equivalent diagnoses. (niams.nih.gov)
References
- Lupus Symptoms, Causes, & Risk Factors | NIAMSniams.nih.gov
- Systemic Lupus Erythematosus (Lupus): Diagnosis, Treatment, and Steps to Takeniams.nih.gov
- Action Plan for Lupus Researchniams.nih.gov
- Systemic lupus erythematosus: MedlinePlus Medical Encyclopediamedlineplus.gov
- Lupus & Kidney Disease (Lupus Nephritis) - NIDDKniddk.nih.gov
- 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosuspubmed.ncbi.nlm.nih.gov
- 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosuspmc.ncbi.nlm.nih.gov
- 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus (SLE): Guideline Summaryrheumatology.org
- EULAR recommendations for the management of systemic lupus erythematosus: 2023 updatepubmed.ncbi.nlm.nih.gov