Diagnosing lupus can be a difficult task. Symptoms can follow tricky patterns, be either mild or severe, and overlap with those of other health concerns. Along with your medical history, healthcare providers use routine and specialized lab tests, and possibly even imaging tests like an MRI or ultrasound, to come to a conclusion.

These can be used as much to rule out lupus as to indicate the disease. Healthcare providers also look for symptoms in more than one of your body’s systems, such as the kidneys and the skin, as lupus is a systemic disease. Unfortunately, some people may suffer for months or years before a diagnosis is finally made.

There are a number of factors that can complicate a lupus diagnosis. Chief among them is the fact that lupus is not one disease but an array of different subtypes, each with their own causes and characteristics. The many challenges facing clinicians include:

  • There are no widely accepted criteria (rules) for diagnosis
  • Lupus is a relapsing-remitting condition, meaning that symptoms can come and go. Until a pattern is recognized, the disease can often go unrecognized.
  • There is not a single blood test that can be used on its own to make the diagnosis.
  • Lupus is a “snowflake” condition, meaning that even if two people have the same subtype, their symptoms can be entirely different.
  • Lupus is a relatively uncommon condition and, as a result, primary care healthcare providers can often overlook or miss symptoms.

Labs and Tests

These are some of the diagnostic tests, many of the screening tests, that healthcare healthcare providers use in conjunction with other tests to help piece together the puzzle.

Complete Blood Count (CBC)

The complete blood count (CBC) screening test has many applications, and it can help identify a wide variety of diseases. Your healthcare provider will likely start with this test.

The CBC can also count additional blood cell types like neutrophils, eosinophils, basophils, lymphocytes, monocytes, and platelets.

In its simplest definition, the CBC is used to measure red and white blood cell count, the total amount of hemoglobin in the blood, hematocrit (the amount of blood composed of red blood cells), and mean corpuscular volume (the size of red blood cells).

A CBC consists of a number of different blood tests and is commonly used as a broad screening tool. The tests that make up a CBC include: 

  • White blood cell count (WBC): White blood cells aid your body in fighting infections and can show if you have an infection as well. This test measures the number of white blood cells in your blood. Too many or too few white blood cells can be an indicator of illness.
  • White blood cell differential: This counts the various types of white blood cells.
  • Red blood cell count (RBC): This measures the number of red blood cells present. Red blood cells contain hemoglobin and function as oxygen carriers. As with white blood cells, both increases and decreases in number can matter.
  • Red cell distribution width: This measures the variation in the size of red blood cells.
  • Hemoglobin: Hemoglobin is the protein in red blood cells that carries oxygen. This measures how much of that oxygen-carrying protein is in the blood.
  • Mean corpuscular hemoglobin: This tells how much hemoglobin is in a red blood cell.
  • Mean corpuscular hemoglobin concentration: This measures the average concentration of hemoglobin inside a red blood cell.
  • Hematocrit: This measures what proportion of the blood volume is made up of red blood cells (as opposed to plasma, the liquid part of blood).
  • Platelet count: This is the number of platelets in the blood. Platelets are a type of blood cell that prevents bleeding by forming clots.
  • Mean platelet volume: This measures the size of platelets and can give information about platelet production in your bone marrow.

Results from the CBC can help detect problems such as dehydration or loss of blood, abnormalities in blood cell production and lifespan, as well as acute or chronic infection, allergies, and problems with blood clotting. Other results may indicate various types of anemia.

If your healthcare provider suspects you have lupus, he or she will focus on your RBC and WBC counts. Low RBC counts are frequently seen in autoimmune diseases like lupus. However, low RBC counts can also indicate blood loss, bone marrow failure, kidney disease, hemolysis (RBC destruction), leukemia, malnutrition, and more. Low WBC counts can point toward lupus as well as bone marrow failure and liver and spleen disease.

If your CBC comes back with high numbers of RBCs or a high hematocrit, it could indicate a number of other issues including lung disease, blood cancers, dehydration, kidney disease, congenital heart disease, and other heart problems. High WBCs, called leukocytosis, may indicate an infectious disease, inflammatory disease, leukemia, stress, and more. 

While this information can help you decipher your lab work, always talk to your healthcare provider if you receive abnormal blood test results. A blood test is just one part of making a diagnosis of lupus. 

Erythrocyte Sedimentation Rate

The erythrocyte sedimentation rate (ESR) test is a blood test that measures inflammation in your body and is used to help diagnose conditions associated with acute and chronic inflammation, including lupus.

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It is usually used in conjunction with other tests, as the test itself is nonspecific. In other words, it can detect increases in inflammation, but it doesn’t pinpoint where the inflammation is or point to a specific disease.

Other conditions can affect outcomes of the test as well. The test is one that is usually conducted several times over a certain period to measure changes in inflammation.

Changes in ESR over time can help guide a healthcare professional toward a possible diagnosis. Moderately elevated ESR occurs with inflammation, but also with anemia, infection, pregnancy, and old age.

A very high ESR usually has an obvious cause, such as a marked increase in globulins that can be due to a severe infection. A rising ESR can mean an increase in inflammation or a poor response to a therapy.

A decreasing ESR can mean a good response, though keep in mind that a low ESR can be indicative of diseases such as polycythemia, extreme leukocytosis, and protein abnormalities.

Urinalysis

This screening test is used to detect substances or cellular material in the urine associated with metabolic and kidney disorders. It’s a routine test, and healthcare providers utilize it to detect abnormalities that often appear before patients suspect a problem.

For those with acute or chronic conditions, regular urinalysis can help monitor organ function, status, and response to treatment. A higher number of red blood cells or a higher protein level in your urine may indicate that lupus has affected your kidneys.

Complement Levels

The complement system is the name of a group of blood proteins that help fight infection. Complement levels, as the name implies, measure the amount and/or activity of those proteins.

Working within the immune system, the proteins also play a role in the development of inflammation. In some forms of lupus, complement proteins are consumed (used up) by the autoimmune response.

A decrease in complement levels can point toward lupus nephritis, kidney inflammation. Normalization of complement levels can indicate a favorable response to treatment.

Antinuclear Antibody Test (ANA)

The antinuclear antibody (ANA) test is used to detect autoantibodies that react against components of the nucleus of the body’s cells. It’s currently one of the most sensitive diagnostic tests available for diagnosing lupus (SLE).

While most people with lupus test positive for ANA, medical conditions such as infections and other autoimmune diseases can give a positive result. For this reason, your healthcare provider may order some other blood tests to correctly diagnose lupus. 

That’s because 97 percent or more of people with lupus (SLE) have a positive ANA test result. A negative ANA test result means lupus (SLE) is unlikely. 

The antinuclear antibody (ANA) assay not only measures the titer (concentration) of auto-antibodies but also the pattern with which they bind to human cells. Certain titer values and patterns are more suggestive of lupus, while others are less so.

As mentioned above, a positive ANA test by itself could indicate one of several other diseases, including drug-induced lupus. Some of those diseases include:

  • Other connective tissue diseases, such as scleroderma and rheumatoid arthritis
  • A reaction to certain drugs
  • Viral illnesses, such as infectious mononucleosis
  • Chronic infectious diseases, such as hepatitis and malaria
  • Other autoimmune diseases, including thyroiditis and multiple sclerosis

Overall, the ANA test should be used if your healthcare provider suspects lupus. If the test result is negative, then lupus is unlikely. If the test result is positive, additional tests are usually required to support the diagnosis. 

Additional Antibody Tests

Additional antibody tests may be used to help support the diagnosis of lupus.

The individual tests evaluate the presence of these antibodies:

  • Anti-double-stranded DNA, a type of antibody found in 70 percent of lupus cases; highly suggestive of SLE
  • Anti-Smith antibodies, found in 30 percent of people with SLE; highly suggestive of SLE
  • Anti-phospholipids antibodies, found in 30 percent of lupus cases and also present in syphilis (explaining why so many people with lupus have false-positive syphilis results)
  • Anti-Ro/SS-A and anti-La/SS-B antibodies, found in a variety of autoimmune diseases, including SLE and Sjogren’s syndrome
  • Anti-histone antibodies, seen in SLE and forms of drug-induced lupus
  • Anti-ribonucleic antibodies, seen in patients with SLE and related autoimmune conditions

Tissue Biopsy

In some cases, your healthcare provider may want to do a biopsy of the tissue of any organs that seem to be involved in your symptoms. This is usually your skin or kidney but could be another organ.

The combination of a positive ANA and either anti-double-stranded DNA or anti-Smith antibodies is considered highly suggestive of SLE. However, not all people ultimately diagnosed with SLE have these autoantibodies.

The tissue can then be tested to see the amount of inflammation there is and how much damage your organ has sustained. Other tests can show if you have autoimmune antibodies and whether they’re related to lupus or something else.

Imaging

Your healthcare provider may also want to do some imaging tests, particularly if you are having symptoms that indicate your heart, brain, or lungs may be affected or if you had abnormal lab results.

X-ray

You may have an x-ray of your chest to look for signs that your heart is enlarged or that your lungs are inflamed and/or have fluid in them.

Echocardiogram

An echocardiogram can indicate problems with your valves and/or your heart. It uses sound waves to create pictures of your heart while it’s beating.

Computed Tomography (CT) Scan

This test may be used if you have abdominal pain to check for problems like pancreatitis or lung disease.

Magnetic Resonance Imaging (MRI)

If you’re having symptoms like memory issues or problems on one side of your body, your healthcare provider may do an MRI to check your brain.

Ultrasound

Your healthcare provider may want to do an ultrasound of your joints if you’re having a lot of pain. If you’re having symptoms that relate to your kidney, you may have an ultrasound of your abdominal area to check for kidney enlargement and blockage.

Differential Diagnoses

Lupus is a notoriously difficult disease to diagnose because its symptoms and test results can indicate so many other possible illnesses. There are far more illnesses that have overlapping symptoms with lupus than can be listed here, but some of the most common ones include:

  • Rheumatoid arthritis (RA): Lupus arthritis and RA have many common symptoms, but the joint disease in RA is often more severe. Also, the presence of an antibody called anti-cyclic citrullinated peptide is found in people with RA but not SLE.
  • Systemic sclerosis (SSc): Similar symptoms between SSc and lupus are reflux and Raynaud’s disease (when your fingers turn blue or white with cold). One difference between SSc and lupus is that anti-double-stranded DNA (dsDNA) and anti-Smith (Sm) antibodies, which are linked to lupus, don’t usually occur in SSc. Another differentiator is that people with SSc often have antibodies to an antigen called Scl-70 (topoisomerase I) or antibodies to centromere proteins.
  • Sjögren’s syndrome: The same organs that may be involved with lupus, such as the skin, heart, lungs, and kidneys, can also manifest in Sjogren’s syndrome. However, there are some symptoms that are more typical of one or the other, and people with Sjogren’s syndrome often have antibodies to Ro and La antigens.
  • Vasculitis: Shared symptoms of both lupus and vasculitis include skin lesions, kidney problems, and inflammation of the blood vessels. One diagnostic difference between vasculitis and lupus is that people with vasculitis tend to be ANA-negative; they also often have antibodies to neutrophil cytoplasmic antigens (ANCA).
  • Behçet’s syndrome: Overlapping symptoms include mouth ulcers, arthritis, inflammatory eye disease, heart disease, and brain disease. People with Behçet’s syndrome tend to be male and ANA-negative, whereas the opposite is true for those with lupus.
  • Dermatomyositis (DM) and polymyositis (PM): While almost all people with lupus have a positive ANA test, only around 30 percent of people with DM and PM do. Many of the physical symptoms are different as well. For instance, people with DM and PM don’t have the mouth ulcers, kidney inflammation, arthritis, and blood abnormalities that people with lupus do.
  • Adult Still’s disease (ASD): Lupus and ASD may share some of the same symptoms, such as fever, swollen lymph nodes, arthritis, and fever. However, people with ASD usually have a negative ANA test and a high white blood cell count, while those with lupus typically have a positive ANA test and a low white blood cell count.
  • Kikuchi’s disease: This disease usually goes into remission on its own within four months and is diagnosed with a lymph node biopsy. Some of the symptoms it has in common with lupus include swollen lymph nodes, muscle pain, joint pain, fever, and, less often, an enlarged spleen and liver.
  • Serum sickness: Overlapping symptoms between serum sickness, an allergic reaction to an injected drug, and lupus may include swollen lymph nodes, skin lesions, fever, and joint pain. However, people with serum sickness tend to be ANA-negative and their symptoms go away once they’ve kicked the allergic reaction, typically within five to 10 days.
  • Fibromyalgia: This one may be a little bit trickier to separate because many people with lupus also have fibromyalgia, symptoms of which include fatigue and joint and muscle pain. However, the photosensitivity, arthritis, and organ involvement that can occur with lupus aren’t found in fibromyalgia.
  • Infections: Those with similar symptoms include Epstein-Barr, HIV, hepatitis B, hepatitis C, cytomegalovirus, salmonella, and tuberculosis. Epstein-Barr may be particularly hard to distinguish from lupus because it also results in a positive ANA test. This is where the specific auto-antibody tests can be helpful.

Healthcare providers are tasked with interpreting test results, then correlating them with your symptoms and other test results. It’s difficult when patients exhibit vague symptoms and clashing test results, but skillful healthcare providers can consider all of these pieces of evidence and eventually determine whether you have lupus or something else entirely. This may take some time along with trial and error.

Diagnostic Criteria

Unfortunately, there are no widely accepted diagnostic criteria for SLE. However, many healthcare providers use the American College of Rheumatology (ACR) 11 common criteria. These criteria were designed to identify subjects for research studies, so they are very stringent.

If you currently have four or more of these criteria or if you’ve had them in the past, chances are very high that you have SLE. However, having less than four doesn’t rule out SLE. Again, additional testing may be necessary to inform a formal diagnosis. These criteria include:

  • Malar rash: You’ve had a rash that’s either raised or flat over your nose and cheeks, called a butterfly rash.
  • Photosensitivity: Either you get a rash from the sun or other UV light, or it makes a rash you already have worse.
  • Discoid rash: You’ve had a rash that’s patchy and raised and may cause scaly lesions that scar.
  • Oral ulcers: You’ve had sores in your mouth that are usually painless.
  • Arthritis: You’ve had pain and swelling in two or more of your joints that doesn’t destroy the surrounding bones.
  • Serositis: You’ve had chest pain that’s worse when you take a deep breath and is caused by inflammation of either the lining around your lungs or the lining around your heart.
  • Kidney disorder: You’ve had continuous protein or cellular casts (bits of cells that should pass through) in your urine.
  • Neurological disorder: You’ve experienced psychosis or seizures.
  • Blood disorder: You’ve been diagnosed with anemia, leukopenia, thrombocytopenia, or lymphopenia.
  • Immunologic disorder: You have anti-double-stranded-DNA, anti-Smith, or positive antiphospholipid antibodies.
  • Abnormal ANA: Your antinuclear antibody test (ANA) was abnormal.

It’s important to note that not all people who are diagnosed with lupus meet four or more of these criteria. Some only meet two or three but have other features that are associated with lupus. This is yet another reminder of how complex this disease can be with a wide range of symptoms that may show up differently in each individual.

Also, read about the symptoms and tests ANA-negative lupus.

Frequently Asked Questions

  • Can lupus be diagnosed with a blood test?
  • There is no one specific test that can diagnose lupus. Diagnosis is based on several tests and excluding other conditions. Blood tests commonly included in a lupus panel include: Complete blood count (CBC)Antinuclear antibodies (ANA) and other antibody testsBlood clotting time tests including prothrombin time (PT)and partial thromboplastin time (PRR) Rheumatoid arthritis factor (RF)Erythrocyte sedimentation rate (ESR)C-reactive protein (CRP)
  • What is usually the first sign of lupus?
  • Lupus symptoms typically first appear between the teen years and 30s. Common early symptoms include fatigue, unexplained fever, hair loss, and a butterfly-shaped rash on the face.
  • What can lupus be mistaken for?
  • Lupus can be difficult to diagnose as its symptoms overlap with several other conditions. Lupus may be confused with rheumatoid arthritis (RA), systemic sclerosis (SSc), Sjögren’s syndrome, vasculitis, Behçet’s syndrome, dermatomyositis (DM) and polymyositis (PM), adult Still’s disease (ASD), Kikuchi’s disease, serum sickness, fibromyalgia, and infections such as Epstein-Barr, HIV, and tuberculosis.

There is no one specific test that can diagnose lupus. Diagnosis is based on several tests and excluding other conditions. Blood tests commonly included in a lupus panel include: 

Lupus symptoms typically first appear between the teen years and 30s. Common early symptoms include fatigue, unexplained fever, hair loss, and a butterfly-shaped rash on the face.

Lupus can be difficult to diagnose as its symptoms overlap with several other conditions. Lupus may be confused with rheumatoid arthritis (RA), systemic sclerosis (SSc), Sjögren’s syndrome, vasculitis, Behçet’s syndrome, dermatomyositis (DM) and polymyositis (PM), adult Still’s disease (ASD), Kikuchi’s disease, serum sickness, fibromyalgia, and infections such as Epstein-Barr, HIV, and tuberculosis.