Systemic Lupus Erythematosus (SLE)

How SLE differs from other forms of lupus

"Lupus" is often used to mean SLE, but there are several forms:

• Systemic lupus erythematosus: affects internal organs as well as skin and joints.
• Cutaneous lupus, including discoid lupus: limited to the skin. A minority of people with discoid lupus later develop SLE.
• Drug-induced lupus: triggered by medicines such as hydralazine, procainamide, isoniazid or TNF inhibitors. It usually affects joints and the lining of the heart and lungs, rarely the kidneys or brain, and improves after stopping the drug.
• Neonatal lupus: a rash, liver or heart problems in a baby born to a mother with anti-Ro or anti-La antibodies.

For a general overview of lupus symptoms, causes and outlook, see lupus. This page looks more closely at how SLE affects each organ and how doctors diagnose and monitor it.

How SLE affects the body, organ by organ

Lupus nephritis

Kidney inflammation is one of the most important complications because it can be silent until advanced. Regular urine tests catch it early. A kidney biopsy classifies it (ISN/RPS classes I to VI) and guides treatment. Modern treatment controls most cases, but some people still progress to kidney failure.

Antiphospholipid antibodies

Up to a third or more of people with SLE have antiphospholipid antibodies. Some develop antiphospholipid syndrome, with blood clots in veins or arteries and pregnancy loss, which requires long-term blood thinners.

Causes and risk factors

SLE results from a combination of:

• Genes: many genetic variants each add a little risk. Having a close relative with lupus or another autoimmune disease increases risk.
• Hormones: estrogen appears to play a role, explaining why women of childbearing age are most affected.
• Environmental triggers: ultraviolet light, viral infections such as Epstein-Barr virus, smoking, silica dust and certain medicines.

SLE is not contagious.

Diagnosis

There is no single test for SLE. A rheumatologist combines symptoms, examination and laboratory results, and rules out other conditions.

Key blood and urine tests

• Antinuclear antibody (ANA): positive in almost everyone with SLE. However, many healthy people, especially women and older adults, have a low-level positive ANA, so a positive ANA alone does not mean lupus.
• Anti-double-stranded DNA (anti-dsDNA): fairly specific for SLE; levels often rise with kidney flares.
• Anti-Smith (anti-Sm): highly specific but found in a minority.
• Complement C3 and C4: often low during active disease.
• Antiphospholipid antibodies: lupus anticoagulant, anticardiolipin and anti-beta-2 glycoprotein I.
• Complete blood count, kidney function and urinalysis with a urine protein-to-creatinine ratio.

The 2019 EULAR/ACR criteria

Rheumatologists use these classification criteria, mainly for research, as a structured checklist:

1. An entry requirement of a positive ANA at a titer of 1:80 or higher.
2. Weighted points across clinical domains: fever, blood counts, neuropsychiatric, skin and mouth, serosal (heart and lung linings), joints and kidneys.
3. Points for immunology: antiphospholipid antibodies, low complement and SLE-specific antibodies.

A total of 10 points or more, with at least one clinical criterion, classifies a person as having SLE. Doctors can still diagnose SLE in someone who does not meet every criterion.

Treatment

Treatment aims for remission or low disease activity, preventing organ damage and limiting steroid exposure.

Medicines for almost everyone

• Hydroxychloroquine: recommended for nearly all people with SLE unless they cannot take it. It reduces flares, protects organs, lowers clot risk and improves survival. It requires a baseline eye exam and yearly retinal screening after 5 years of use, or sooner with risk factors.
• Sun protection with broad-spectrum sunscreen and clothing.

Controlling active disease

• Corticosteroids such as prednisone for flares, tapered to the lowest dose possible or stopped, because long-term steroids cause bone loss, diabetes, cataracts and infections.
• Immunosuppressants: methotrexate, azathioprine or mycophenolate for joint, skin or organ disease and to allow steroid reduction.
• Biologics: belimumab (which blocks B-cell survival) and anifrolumab (which blocks type I interferon) for active disease despite standard treatment.

Lupus nephritis treatment

Induction treatment usually combines steroids with mycophenolate or low-dose intravenous cyclophosphamide, often adding belimumab or the calcineurin inhibitor voclosporin. Blood pressure medicines that reduce protein in the urine (ACE inhibitors or ARBs) protect the kidneys.

Protecting long-term health

• Blood pressure, cholesterol and blood sugar control, because heart disease is a leading cause of death in SLE
• Bone protection with calcium, vitamin D and sometimes osteoporosis medicines when on steroids
• Vaccinations against flu, pneumococcus, COVID-19 and shingles (non-live vaccine)
• Not smoking, which worsens lupus and reduces the benefit of hydroxychloroquine

Pregnancy

Most women with SLE can have successful pregnancies, but they are higher risk. Ideally, conceive when the disease has been quiet for at least 6 months on pregnancy-compatible medicines. Hydroxychloroquine is continued. Mycophenolate, methotrexate and cyclophosphamide must be stopped well before conception. Low-dose aspirin is advised to reduce preeclampsia risk. Women with anti-Ro antibodies are monitored for heart block in the baby.

Outlook

Survival has improved dramatically: today most people with SLE live 10 years or more after diagnosis, many with a near-normal lifespan. The main threats are kidney disease, infections, heart disease and side effects of long-term steroids. Regular checkups, usually every 3 to 6 months with blood and urine tests, help catch flares and organ involvement early.

Frequently asked questions

What is the difference between lupus and systemic lupus erythematosus?

Lupus is a family of autoimmune conditions. Systemic lupus erythematosus is the most common and serious type, affecting internal organs as well as skin and joints. Other types include cutaneous lupus, which affects only the skin, drug-induced lupus and neonatal lupus. When people say "lupus" they usually mean SLE.

What are the first signs of SLE?

Common early signs are fatigue, joint pain and swelling, low-grade fevers, a rash across the cheeks and nose or rashes after sun exposure, mouth sores, hair thinning and fingers that turn white in the cold. Symptoms often come and go, which can delay diagnosis.

Does a positive ANA mean I have lupus?

No. A positive ANA is found in almost everyone with SLE, but also in many healthy people and in other conditions such as thyroid disease or infections. Lupus is diagnosed only when a positive ANA occurs with typical symptoms and other test findings such as anti-dsDNA antibodies or low complement.

What organs does SLE affect?

SLE most often affects the joints, skin, blood cells and kidneys. It can also inflame the linings of the heart and lungs, causing chest pain, and affect the brain and nerves, causing headaches, seizures, mood changes or memory problems. Which organs are involved varies greatly between people.

Why is hydroxychloroquine so important in SLE?

Hydroxychloroquine reduces flares, lowers the risk of organ damage and blood clots, improves cholesterol and blood sugar, and is linked to longer survival. It is recommended for nearly everyone with SLE, including during pregnancy. Annual eye screening after 5 years checks for rare retinal toxicity.