How Lupus Is Diagnosed

Systemic lupus erythematosus (SLE), otherwise known as lupus. can be difficult to diagnose. Symptoms can follow tricky patterns, be mild or severe, or overlap with symptoms of other diseases.

A diagnosis of lupus can be made based on a physical exam, a review of your medical history, blood tests, and imaging studies like an MRI or ultrasound. To confirm the diagnosis, all other possible causes of your symptoms must be excluded.

Because of the complexity of diagnosis, some people with lupus can go months or years before a definitive diagnosis is received.

This article explains how lupus is diagnosed, including the diagnostic criteria, the tests involved in the investigation, and the diseases investigated as part of the differential diagnosis (made after ruling out other causes).

Challenges Diagnosing Lupus

There are many things 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 its distinctive causes and characteristics.

The main challenges of diagnosing lupus include:

• Disease frequency: Lupus is a relatively uncommon condition, affecting 20 to 150 people per 100,000. As a result, healthcare providers can often overlook or miss symptoms.
• Diagnostic guidelines: There are no widely accepted criteria (rules) for diagnosis.
• Disease patterns: Lupus is a relapsing-remitting condition, meaning that symptoms can come and go. Until a pattern is recognized, the disease may go unrecognized.
• Testing limitations: There is no single blood test or imaging study used to diagnose lupus.
• Variations in symptoms: Lupus is a "snowflake" condition, meaning that even if two people have the same subtype, their symptoms can be entirely different.
  

Diagnostic Criteria

There is no single blood or imaging test to definitively diagnose lupus. Because it can mimic other diseases, including other autoimmune diseases like rheumatoid arthritis, it’s important to consult a specialist in autoimmune diseases known as a rheumatologist.

The diagnosis of lupus involves different blood tests and imaging studies but is ultimately based on a set of criteria that a person must meet in order to be diagnosed.

If you have at least four of the following symptoms with no other causes—even if they appear just once or come and go—you may be diagnosed with lupus:

• A butterfly-shaped (malar) rash across the bridge of your nose and on the cheeks
• A scaly, reddish rash on both arms, both legs, the neck, torso, or fingers of both hands
• A photosensitivity rash caused by exposure to the sun
• Painless sores on the roof of the mouth or inside the nose
• Stiff, swollen, or painful joints in the arms and legs that may also be hot
• Blood tests that show low red blood cells, low white blood cells, or low platelets
• Organ inflammation diagnosed by blood and imaging tests, such as pleurisy (a type of lung inflammation), myocarditis (heart muscle inflammation), arthritis (joint inflammation), and nephritis (kidney inflammation)
• Nervous system disorders like seizures, psychosis, hallucinations, or delusions
• Signs of kidney disease, such as proteinuria (high protein in urine) or hematuria (blood in urine)
• Blood tests that reveal abnormal immune proteins, called autoantibodies, seen with lupus and other autoimmune diseases

Autoantibody Tests

Under normal circumstances, the immune system will release immune proteins called antibodies that "recognize" and attack disease-causing organisms (pathogens). Autoantibodies are immune proteins that mistakenly attack normal cells thinking they are pathogens.

There is no single autoantibody associated with lupus—some of the following occur with other autoimmune diseases. However, their presence can help confirm the diagnosis.

Antinuclear Antibody Test (ANA)

The antinuclear antibody (ANA) test is one of the most sensitive tests to help diagnose lupus. All told, around 97% of people with lupus will have a positive ANA test result. A negative ANA test result means that lupus is unlikely. 

With that said, other diseases or conditions can trigger an ANA positive result, including:

• Other connective tissue diseases, such as scleroderma and rheumatoid arthritis
• Viral illnesses, such as infectious mononucleosis
• Chronic infectious diseases, such as hepatitis and malaria
• Other autoimmune diseases, including thyroiditis and multiple sclerosis
• Certain drug reactions

The ANA test not only measures the titer (concentration) of autoantibodies in a sample of blood but also the pattern with which they bind to cells. Certain titer values and patterns are more suggestive of lupus than others.

Note that 20% of otherwise healthy individuals can have a low titer positive ANA, so ANA should not be used as a screening test unless there is a high pre-test suspicion for lupus.

Additional Antibody Tests

Additional antibody tests may be used to support the diagnosis of lupus, including:

• Anti-double-stranded DNA (dsDNA): Found in 70% of lupus cases
• Anti-Smith (Sm) antibodies: Found in 30% of lupus cases
• Antiphospholipid antibodies: Found in 30% of lupus cases as well as syphilis
• Anti-Ro/SS-A and anti-La/SS-B antibodies: Found with a variety of autoimmune diseases, including lupus and Sjogren's syndrome
• Anti-ribonucleic antibodies: Also found with lupus and other autoimmune conditions 

Blood Tests

There are many blood tests involved in the diagnosis of lupus. They are used mainly to diagnose features of the disease rather than the disease itself. They may also be used to exclude other causes.

Complete Blood Count (CBC)

The complete blood count (CBC) is a panel of tests used to evaluate the composition of cells in a sample of blood.

With lupus, one of the primary aims is to determine whether autoantibodies are attacking organs that produce blood cells, causing numbers to drop.

These include blood tests like:

• Red blood cell count (RBC): This measures red blood cells (erythrocytes) that deliver oxygen to tissues and can diagnose anemia (low red blood cells).
• White blood cell count (WBC): This measures white blood cells (leukocytes) and can diagnose leukopenia (low white blood cells).
• Platelet count: This measures red blood cells (platelets) that clot blood and can diagnose thrombocytopenia (low platelets).
  

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Erythrocyte Sedimentation Rate

The erythrocyte sedimentation rate (ESR) is a blood test that measures generalized inflammation in the body. Many diseases cause a high ESR, so the test is mainly used to differentiate inflammatory conditions like lupus from non-inflammatory ones like fibromyalgia.

A high ESR may point the healthcare provider in the direction of a lupus-associated condition, like lupus nephritis, for which additional tests may be needed.

C-reactive protein (CRP) is another marker of general inflammation. But unlike ESR, it doesn't typically rise with lupus flares.

Urinalysis

Urinalysis can detect abnormal substances in your urine. One of the goals with lupus is to check if there are any abnormalities associated with lupus nephritis, including proteinuria and hematuria.

When the kidneys are damaged by lupus, excess protein can leak into your urine. There may also be bleeding that is invisible (microscopic) or visible (gross). A high number of red blood cells or protein in your urine may be a sign of lupus nephritis.

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 these proteins.

These proteins also play a role in spurring inflammation in the body. In some forms of lupus, complement proteins are depleted by the autoimmune response. A decrease in the complement level is often seen with lupus nephritis.

Tissue Biopsy

In some cases, your healthcare provider will want to do a biopsy of your skin, kidney, or other organs to see if you have signs of lupus. The tissue can be tested to check for signs of inflammation or tissue death (necrosis). Other tests can show if you have autoantibodies related to lupus.

Imaging Studies

Your healthcare provider may want to order imaging tests, particularly if you are having symptoms of heart, brain, or lung inflammation.

Options include:

• Chest X-ray: This plain film radiographic study may detect signs of fluid in the lungs (pleural effusion).
• Echocardiogram: This non-invasive imaging technique may detect pericarditis, or pericardial effusion.
• Computed tomography (CT): This test, which composites multiple X-ray images, can detect inflammatory changes in organs throughout the body.
• Magnetic resonance imaging (MRI): This imaging technique can create highly detailed images of soft tissues and may be useful in detecting brain inflammation.

Differential Diagnoses

Lupus is notoriously difficult to diagnose because its symptoms mimic those of other diseases. Because there is no single test to identify lupus, healthcare providers must investigate and exclude all other causes as part of the differential diagnosis.

These include:

• Rheumatoid arthritis (RA): Lupus arthritis and RA have many common symptoms, but RA joint disease is often more severe. Also, the presence of an antibody called anti-cyclic citrullinated peptide (CCP) is found in people with RA but not lupus. 
• Scleroderma: Scleroderma and lupus can both cause skin lesions and Raynaud's disease (where your fingers turn blue or white with cold). However, dsDNA and Sm antibodies are seen with lupus but not scleroderma.
• Sjögren's syndrome (SJS): The same organs involved with lupus (such as the skin, heart, lungs, and kidney) are also involved with SJS. However, people with SJS will not have positive dsDNA or Sm antibodies, and the associated dryness will be much more significant.
• Vasculitis: Lupus and vasculitis can both cause skin lesions, kidney problems, and inflammation of the blood vessels. However, people with vasculitis tend to be ANA-negative and have a type of autoantibody called anti-neutrophil cytoplasmic antigens (ANCA).
• Behçet's syndrome: Overlapping symptoms of lupus and Behçet's syndrome include mouth ulcers, arthritis, inflammatory eye disease, and heart disease. People with Behçet tend to be ANA-negative, whereas the opposite is true for those with lupus.
• Dermatomyositis and polymyositis: While almost all people with lupus have a positive ANA test, only around 30% of people with dermatomyositis (DP) and polymyositis (PM) do. These conditions characteristically have severe weakness, which is not typically seen in SLE. Also, mouth ulcers, nephritis, arthritis, and anemia seen with lupus are not seen with DP or PM.
• Adult Still's disease (ASD): Lupus and ASD can both cause fever, swollen lymph nodes, and arthritis. However, people with ASD usually have a negative ANA test and a high WBC, while those with lupus typically have a positive ANA and a low WBC.
• Kikuchi's disease: Kikuchi's disease can look like lupus with swollen lymph nodes, muscle or joint pain, and fever, but it usually goes into remission on its own within four months. It can also diagnosed with a lymph node biopsy.
• Fibromyalgia: Many people with lupus also have fibromyalgia. Both can cause fatigue and joint or muscle pain, but photosensitivity, arthritis, and organ inflammation seen with lupus are not seen with fibromyalgia. Fibromyalgia has no associated lab abnormalities and is not an autoimmune disease.
• Infections: Those with similar symptoms include Epstein-Barr virus, HIV, hepatitis B, hepatitis C, cytomegalovirus, and tuberculosis. These can all be diagnosed with blood tests.

Summary

Lupus can be difficult to diagnose because it can cause many different systems based on which organs are involved. There is no single lab test or imaging study able to diagnose lupus, so a lengthy diagnosis may be needed to determine if the symptoms meet the diagnostic criteria for lupus. All other possible causes must also be excluded.

The diagnosis of lupus typically involves a physical exam, a review of your medical history, autoantibody tests, various blood tests, and imaging studies.