Key takeaways

  • Nearly all people who have systemic lupus erythematosus (SLE) test positive for antinuclear antibody (ANA), but a small number can develop lupus without ANA, known as seronegative or ANA-negative lupus.
  • Symptoms of seronegative lupus are generally the same as SLE and include fatigue, fever, skin rash, and joint pain and swelling; although research suggests low platelet counts may be more common in ANA-negative lupus.
  • Doctors diagnose seronegative lupus using a combination of medical history, physical exam findings, imaging, and additional lab tests, and the treatment approach is similar to SLE.

Lupus is an autoimmune disease that can cause problems with many organs, such as your skin, kidneys, and joints.

Around 204,000 people in the United States are are living with systemic lupus erythematosus (SLE), the most common type of lupus. Women are diagnosed more frequently than men, and certain racial and ethnic groups are at a higher risk of developing SLE.

Lupus is difficult to diagnose, unless evaluated by a specialist, like a rheumatologist. No single test can confirm the diagnosis, and symptoms overlap with many other conditions. Doctors use a combination of exams, tests, and imaging to diagnose lupus, including:

  • reviewing your personal and family medical history
  • asking you about your symptoms
  • examining you for characteristic signs of lupus
  • ordering labs tests
  • taking x-rays
  • ruling out other diseases (autoimmune, infectious, cancers) that can mimic lupus

One of the characteristic signs of SLE is an antinuclear antibody (ANA) in your blood. ANA is found in the blood of about 96.8–99.8% of people with SLE.

A very small number of people who test negative for ANA in the blood still have the condition. In some cases, this is due to the type of test used, as some are more effective than others at detecting ANA.

When this happens, it’s called seronegative lupus or ANA-negative lupus.

A type of white blood cell called a B cell produces antibodies when it detects harmful cells or microbes. Antibodies neutralize these perceived threats and signal other immune cells to destroy them.

In people with lupus, white blood cells mistake healthy cells as harmful. This autoimmune reaction produces a type of antibody called ANA (antinuclear antibody). ANA is also found in the blood of people with some other autoimmune diseases like Sjögren disease and scleroderma.

Doctors measure levels of ANA with an ANA blood test. About 96.8–99.8% of people with SLE have ANA in their blood. However, testing positive for ANA isn’t enough to confirm an SLE diagnosis.

Up to 15% of people without a definite autoimmune disease also test positive for ANA. ANAs can appear in the blood years before the development of an autoimmune condition.

It’s important to note that COVID-19 infections can also trigger antibodies like ANA, and they can persist for prolonged period of time.

The signs and symptoms of SLE for people with ANA-negative SLE are similar to those for people with ANA-positive SLE.

Signs and symptoms of SLE can include:

  • fatigue
  • fever
  • joint pain and swelling
  • skin rash
  • swelling in the feet or eyes
  • ulcers in the mouth or nose

In a 2022 study, researchers found that a low platelet count was more prevalent among ANA-negative SLE than ANA-positive SLE.

SLE is caused by an autoimmune reaction where your immune system attacks healthy cells in your body. Researchers do not know why this happens, but a combination of genetics and environmental factors as well as immune and inflammatory influences are thought to play a role.

Some people with SLE don’t have ANA in their blood, but they may have other types of antibodies seen in autoimmune disease.

Findings from a 2022 study suggests that ANA-negative SLE is particularly common with prolonged use of glucocorticoids or immunosuppressants.

There are no diagnostic criteria for SLE, only several classification criteria. The most recent are the 2019 criteria from the ACR and European League Against Rheumatism (EULAR), which require a positive ANA test at least once to classify an autoimmune disease as SLE.

That said, ANA-negative lupus may still be diagnosed based on a combination of exam findings, symptoms, imaging, and test results. It just would not meet classification criteria to enroll in a clinical trial.

SLE doesn’t have a cure, but medications can help you manage your symptoms. Treatment for seronegative lupus are the same as SLE. Your doctor may recommend treatments such as:

  • antimalarial drugs
  • steroids
  • nonsteroidal anti-inflammatory drugs (NSAIDs)
  • immunosuppressants
  • monoclonal antibodies
  • blood thinners

It’s important to see a doctor any time you notice potential symptoms of lupus. Regular follow-ups are also essential. It’s critical to tell your doctor if:

  • your symptoms are getting worse
  • you develop new symptoms
  • your treatment doesn’t seem to be helping
Medical emergency

Lupus can cause many severe complications. Call emergency medical services or go to the nearest emergency room if you notice potentially life threatening complications like:

  • trouble breathing
  • coughing up blood
  • chest pain
  • weakness or numbness in the arms or legs
  • confusion, altered mental state, hallucinations, or psychosis
  • severe headache
  • trouble speaking
  • a fever over 101°F (38°C)
  • severe stomach pain
  • bleeding or bruising easily
  • changes in urine (low output or dark, bloody urine)

The outlook for people with SLE varies widely. The current 5-year survival rate is about 91%, with the 8-year survival rate around 89%.

With proper treatment, many people with SLE live a full typical lifespan.

It’s important to note that the leading causes of early death in SLE are:

  • heart disease
  • kidney disease
  • serious infections

Lupus is often referred to as “the great imitator” since it’s mistaken for other diseases in as many as 40% of cases.

Some of the common conditions that lupus can mimic include:

  • rheumatoid arthritis
  • Sjögren disease
  • adult-onset Still disease
  • Behcet disease
  • scleroderma
  • dermatomyositis
  • vasculitides
  • sarcoidosis
  • lymphomas
  • multiple sclerosis
  • fibromyalgia
  • viral infections such as parvovirus B19, hepatitis B or C, or Epstein-Barr virus

Most people who have lupus test positive for anti-nuclear antibodies (ANA), which is a common blood test used to help diagnose the disease. However, a small number of people with lupus do not have ANA in their blood.

Sometimes, ANA levels can change over time, making it possible to have a positive ANA test and then not have detectable levels of ANA on future tests. ANA can also be found in people who do not have lupus or another autoimmune disease.

Because of this, doctors do not rely on ANA alone to diagnose lupus. They also look at symptoms, physical exams, and other lab test and imaging together. It’s important to work closely with your doctor to understand your results and get the right care.