Can You Test Negative for Lupus and Still Have it?

A very small number of people who test negative for antinuclear antibody (ANA) in the blood, which is a sign of the most common type of lupus, still have the condition.
Lupus is an autoimmune disease that can cause problems with many organs, such as your skin, kidneys, and joints.
According to the Centers for Disease Control and Prevention (CDC), it’s estimated that 5.1 people per 100,000 in the United States are diagnosed with lupus each year. Women are diagnosed more frequently than men.
Lupus is difficult to diagnose since no one test can provide a definitive diagnosis. Doctors use a combination of tests and procedures including:
examining your personal and family medical history
asking you about your symptoms
examining you for characteristic signs of lupus
ordering blood and urine tests
ordering skin and kidney biopsies
The most common type of lupus is called systemic lupus erythematosus (SLE). 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 small percentage of people can test negative for ANA but still have SLE. 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.
What is an ANA test?
A type of white blood cell called a B cell produces antibodies when it detects harmful cells. 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. ANA are 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 for an SLE diagnosis. According to the American College of Rheumatology (ACR), up to 15% of people without autoimmune disease also test positive for ANA.
It’s important to note that COVID-19 infections can also trigger autoantibodies like ANA, and they can persist for prolonged period of time.

Seronegative lupus symptoms and signs

Seronegative lupus symptoms and signs
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:
muscle and joint pain and swelling
a butterfly-shaped rash across your nose and cheeks
other rashes
hair loss
fever
kidney problems
fatigue
mouth sores
anemia
memory problems
chest pain
In a 2022 study, researchers found that a low platelet count was more prevalent among ANA-negative SLE than ANA-positive SLE.
Two ANA-negative SLE case studies
In a 2020 case study, researchers reported on a 28-year-old man with ANA-negative SLE. He presented with:
a butterfly-shaped rash on his face
severe swelling in his legs
abnormal amounts of protein in his urine
In another 2020 case study, researchers reported on a 45-year-old female who presented with:
dry cough
worsening breathlessness
mild paleness
swelling in her leg
a non-healing ulcer on her ankle

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What causes seronegative lupus?

What causes seronegative lupus?
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 are thought to play a role.
Learn more about the potential cause of lupus.
Some people with SLE don’t have ANA in their blood, but they may have other types of antibodies that suggest an autoimmune reaction.
Other autoantibodies include:
anti-double stranded DNA bodies, specific to lupus
anti-Sm antibodies, specific to lupus
anti-Ro and anti-La antibodies
anti-histone antibodies
anti-RNP antibodies
In one 2020 study, research suggests that ANA-negative SLE is particularly common with prolonged use of glucocorticoids or immunosuppressants.

How is lupus diagnosed if ANA is negative?

How is lupus diagnosed if ANA is negative?
The 2019 criteria from the ACR and European League Against Rheumatism (ELAR) note requiring a positive ANA test at least once to classify an autoimmune disease as SLE. Under this system, ANA-negative lupus would not be classified as SLE. Some doctors may refer to it as a “lupus-like” disease.
Along with requiring a positive ANA test, the ACR/ELAR criteria uses a point system to diagnose lupus depending on how many characteristic features you have. For example, fever is 13 points, and seizures are 34 points.
A score over 83 is required for a diagnosis of SLE out of a maximum of 305 points.

How is seronegative lupus treated?

How is seronegative lupus treated?
SLE doesn’t have a cure, but medications can help you manage your symptoms. The treatments for seronegative lupus are the same as SLE. Your doctor may recommend treatments like:
nonsteroidal anti-inflammatory drugs (NSAIDs)
corticosteroids
antimalarial drugs
immunosuppressants or chemotherapy
BLyS-specific inhibitors

When to contact a doctor

When to contact a doctor
It’s important to see a doctor any time you notice potential symptoms of lupus like a butterfly-shaped rash on your face or an unexplained fever. Regular follow-ups are also essential. It’s critical to tell the doctor if:
you develop new symptoms
your medications lose their effect
your symptoms are getting worse
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 speaking
trouble breathing
rapid heartbeat
chest pain
cognitive changes
new seizures
new skin rashes (which can indicate inflammation in blood vessels, a condition known as vasculitis)

What is the outlook for living with seronegative lupus?

What is the outlook for living with seronegative lupus?
The outlook for people with SLE varies widely, but it has improved significantly over the last several decades. Recent studies have reported 5-year survival rates over 93% compared to under 50% in the 1950s.
With proper treatment, many people with SLE live a full typical lifespan.
It is important to note that the leading causes of early death are:
cardiovascular disease
infections
kidney disease

What other conditions can mimic lupus symptoms?

What other conditions can mimic lupus symptoms?
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 conditions that lupus can mimic include:
rheumatoid arthritis
adult-onset Still disease
Behcet’s disease
sarcoidosis
viral infections such as parvovirus B19 infection
infectious endocarditis
lymphomas
autoimmune thyroid disease
celiac disease
myasthenia gravis
polio
Sjögren’s disease

Takeaway

Takeaway
Most people with lupus test positive for ANA. However, it’s not uncommon for people without autoimmune diseases to also test positive for ANA.
A small number of people with lupus do not have ANA circulating through their blood. It’s also possible to have a positive ANA test and then not have detectable levels of ANA on future tests.
The newest diagnostic criteria for SLE require at least one positive ANA test.