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Diagnosing Systemic Lupus Erythematosus

Systemic lupus erythematosus, commonly known as lupus, is a chronic autoimmune disease. This means that the immune system, which attacks viruses and bacteria, instead attacks healthy tissue, causing inflammation throughout the body and, sometimes, damaging tissue. Lupus can affect the blood vessels, brain, joints, kidneys, heart, lungs, nervous system, or skin. Another type of lupus, cutaneous (discoid) lupus, affects only the skin.

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Symptoms of lupus can range from mild to serious, depending on the organs affected. Lupus involves periodic flare-ups, in which symptoms intensify, and remission, in which symptoms lessen or disappear. The most common symptoms include fatigue, painful and swollen joints, skin rashes—most notably, a butterfly-shaped rash across the face—unexplained fever, and mouth or nose ulcers. More severe lupus can cause pleuritis, an inflammation of the lining of the lungs; kidney disease; neurological conditions—those affecting the brain and spinal cord—such as weakness or memory loss; and pericarditis, an inflammation of the sac that covers the heart.

Experts don’t know what causes lupus. But a family history of the disease increases risk, and hormones or chemicals may also play a role. In people with a family history of lupus, exposure to sunlight can trigger symptoms. Lupus affects 10 times more women than men and more African Americans. It is most common in women between the ages of 15 and 40.

Systemic lupus erythematosus is a lifelong condition. Your NYU Langone rheumatologist, a doctor specializing in conditions such as arthritis and lupus that cause pain and swelling in joints and other tissues, can help you successfully manage the symptoms for the long term.

Diagnostic Criteria

Systemic lupus erythematosus can be difficult to diagnose: no single blood or imaging test can definitively identify it, and its symptoms can be vague, progress slowly, change, or mimic other conditions, such as rheumatoid arthritis. As a result, it’s important to consult a rheumatologist.

After conducting a physical exam and taking your medical history, your doctor orders tests based on your symptoms. If you have at least four of the following signs and symptoms with no other known causes, even if they appear just once or come and go, you may be diagnosed with lupus.

Three Types of Skin Rash

Each of the three following kinds of rash constitutes one criterion for diagnosing lupus: a butterfly-shaped (malar) rash across the bridge of the nose and onto the cheeks; a red or purple scaly rash on both arms, the fingers of both hands, the neck, the torso, or the legs; a rash resulting from photosensitivity—that is, exposure to sunlight.

Mouth Sores

Ulcers may appear on the roof of the mouth or inside the nose and are typically painless.

Joint Problems

Stiff, swollen, or painful joints in the arms and legs may also be hot to the touch.

Reduced Levels of Blood Cells

A blood test may find lower-than-usual numbers of red blood cells, which carry oxygen to organs and tissues; platelets, which aid in blood clotting; or white blood cells, which fight infection.

Organ Inflammation

An inflammation in the lining of the lungs, called pleurisy, or in the sac surrounding the heart, called pericarditis, can cause chest pain and may signify lupus. Sometimes, systemic lupus erythematosus can lead to lupus nephritis, which is a serious inflammation of the kidneys.

Nervous System Disorders

When lupus affects the nervous system, a person may experience seizures or psychosis, including hallucinations or delusions—that is, thoughts that don’t match up to reality.

Autoantibody Activity

Antibodies normally fight infections. But in lupus, antibodies become autoantibodies and mistakenly attack the body’s healthy tissues, recruiting other cells and proteins to help, causing inflammation.

Urine Changes and Kidney Disease

Urine abnormalities, such as high levels of protein in the urine, can indicate that lupus has affected the kidneys. Some people develop lupus nephritis, an inflammation of the kidneys that can cause them to leak protein and blood cells into urine. Left untreated, this can lead to kidney failure.

Symptoms of kidney disease also often include swelling of the ankles, feet, legs, and, less commonly, the face or hands, as well as puffy eyes upon waking. Dark-colored and foamy urine, high blood pressure, and weight gain may also appear. After speaking with you about your symptoms, including those you may have had in the past or that come and go, your NYU Langone rheumatologist orders a series of diagnostic tests.

Autoantibody Tests

Normally, antibodies in the blood repel invading viruses and bacteria. Autoantibodies mistakenly target a person’s own healthy tissues. Your doctor may perform a series of blood tests to check for autoantibodies in the blood, which are common with lupus.

Antinuclear Antibody Tests

An antinuclear antibody (ANA) blood test measures the presence of antibodies that are directed against the body’s cells, a sign of systemic lupus erythematosus. ANA is present in nearly everyone with active lupus.

It’s important to know that because some healthy people can also have a positive ANA, a positive result doesn’t necessarily mean that you have lupus. Positive results on the ANA test may indicate other autoimmune disorders, such as certain kinds of thyroid disease and rheumatoid arthritis. Doctors may consider other criteria to help diagnose or rule out lupus.

If you test positive for ANA, your NYU Langone rheumatologist may order tests for anti-double-stranded DNA, anti-SSA/RO, and anti-Smith antibodies to get more detailed information.

Anti-Double-Stranded DNA Antibody Tests

People with lupus often have an antibody in the blood called anti-double-stranded DNA, also known as anti-dsDNA. This antibody targets double-stranded DNA, the material that makes up the body’s genetic code. As lupus becomes more active, the level of anti-dsDNA autoantibodies can rise, indicating a greater risk of lupus nephritis, which can lead to kidney failure.

Anti-SSA/Ro Antibody Tests

Doctors may order an anti-SSA/Ro antibody test to look for Sjogren’s syndrome, an autoimmune disease that causes severe dryness in the eyes and mouth. Some of its symptoms, such as joint pain and skin rashes, mimic those of lupus, and people with lupus can have Sjogren’s syndrome at the same time. Because this antibody can also be associated with rashes caused by exposure to sunlight, people who test positive should take extra caution when outdoors by wearing hats and sunscreen.

Rarely, these antibodies can lead to complications during pregnancy, and so pregnant women who have tested positive for this antibody require extra monitoring.

Anti-Smith Antibody Tests

The anti-Smith antibody, also known as the anti-Sm antibody, targets the body’s own proteins and is found almost exclusively in people with lupus. Though not all people with lupus have this antibody, those who do usually receive a diagnosis of lupus.

Antiphospholipid Antibodies Tests

Antibodies associated with increased risk of forming blood clots are commonly found in people with lupus. These antibodies are also found in people with antiphospholipid syndrome, an autoimmune disease associated with excessive blood clotting.

Additional Blood Tests

Your NYU Langone doctor may recommend other blood tests to check for inflammation. These may include an erythrocyte sedimentation rate (ESR) test or a C-reactive protein (CRP) test. Results showing increases in either of these tests can indicate inflammation or infection in the body, but the tests don’t identify its location.

Blood tests that measure the activity of the complement system, a network of proteins that work together to eliminate foreign invaders, may also be performed. Decreased levels of C3 and C4 complements can indicate active lupus. The doctor draws blood from your arm and sends it to a laboratory for results, which take up to a week to be completed.


Doctors use urinalysis to look for high levels of protein or red blood cells in the urine, which can indicate kidney damage. Your doctor may ask you to collect urine for 24 hours in supplied containers.


Your doctor may recommend a kidney biopsy if he or she suspects kidney damage because of your symptoms or the results of a urinalysis. In this procedure, a small piece of tissue is removed for analysis. First, your doctor numbs the skin on your back near the kidneys with a local anesthetic. Then, using ultrasound for guidance, the doctor injects a needle into one kidney to draw out a tissue sample. You can return home the same day and resume normal activity the next day.

Your doctor may refer you to a dermatologist for a skin biopsy, the analysis of a small sample of skin. He or she may perform a “lupus band test,” which checks for lupus-related antibodies. The doctor injects an area of the skin with a local anesthetic, then uses a punch, an instrument with a sharp circular edge, to remove a core of skin for testing. In some situations, a stitch may be used to close the wound.

CT Scans

Your NYU Langone rheumatologist may order CT scans of your heart, joints, kidneys, or lungs to check for the causes of your symptoms. A CT scan uses X-rays to create detailed, three-dimensional images of organs. Before the test, you may drink a liquid contrast dye that makes certain organs more easily visible. It leaves your body hours later in the urine or stool.


An echocardiogram is an ultrasound test that uses sound waves to create images of the heart. It allows the doctor to evaluate how well your heart is functioning.

MRI Scans

In MRI a magnetic field and radio waves are used to create computerized, three-dimensional images of organs that lupus may be affecting. Your doctor may order an MRI if it appears that lupus has affected the central nervous system, which includes the brain and the spinal cord, and is causing confusion or “brain fog,” depression, seizures, or psychosis.

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