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Lupus is a chronic disease that can be complex and difficult to diagnose. Lupus symptoms can imitate symptoms of other diseases, are sometimes mild, and often come and go. Your doctor will use your past medical history, a physical exam, and many routine, as well as specialized tests, to help diagnose lupus.
Given the important role that laboratory test data play in medical decision-making, it is important to understand the many clinical lab tests that are used in the diagnosis, routine care and medical treatment of lupus.
Who Can Diagnose Lupus?
Although mild cases of lupus can be diagnosed and treated by family practitioners, internists and general practitioners, people often ask, “Who is the specialist for lupus?” The dermatologist is recognized as the specialist for diagnosing and treating lupus of the skin. The rheumatologist is recognized as the specialist when it comes to diagnosing and treating systemic lupus.
How Is Lupus Diagnosed?
No single lab test can determine whether an individual has lupus. Many physicians use the American College of Rheumatology’s “Eleven Criteria of Lupus” to help diagnose lupus and distinguish it from other diseases. The criteria include symptoms as well as specific laboratory tests which provide information about a person’s immune system. In most cases, an individual should have four or more of these symptoms to suspect lupus. The symptoms do not have to occur at the same time.
The “Eleven Criteria of Lupus”
- Malar rash: butterfly-shaped rash across cheeks and nose
- Discoid (skin) rash: raised red patches
- Photosensitivity: skin rash as a result of reaction to sunlight
- Mouth or nose ulcers: usually painless
- Nonerosive Arthritis (bones around joints do not get destroyed): in 2 or more joints with tenderness, swelling, or effusion
- Cardio-pulmonary involvement: inflammation of the lining around the heart (pericarditis) and/or lungs (pleuritis)
- Neurologic disorder: seizures and/or psychosis/cognitive dysfunction
- Renal (kidney) disorder: excessive protein in the urine, or cellular casts in the urine
- Hematologic (blood)`disorder: low red blood cell count (hemolytic anemia), low white blood cell count (luekopenia), or low platelet count (thrombocytopenia)
- Immunologic disorder: antibodies to double stranded DNA, antibodies to Sm, positive antiphospholipid antibody such as anticardiolipin, or false positive syphilis test (VDRL)
- Antinuclear antibodies (ANA): positive test in absence of drugs known to induce it
Early diagnosis is extremely important. It can lead to effective treatment which can minimize symptoms, reduce inflammation and pain, help maintain normal body functions, and prevent serious complications.
What Blood Tests Are Used to Diagnosis Systemic Lupus?
Antinuclear antibody (ANA)/immunofluorescent antinuclear antibody (FANA)
The ANA test is positive in more than 95% of individuals with systemic lupus, and is used to determine if autoantibodies to cell nuclei are present in the blood. At this time, the ANA test is the most sensitive diagnostic test available for confirming the diagnosis of systemic lupus, however, it is NOT a lupus test. If three or more clinical features, such as skin, joint, kidney, lung, heart, blood or central nervous system findings are present, a positive ANA test may confirm the disease. However, it is important to understand that a positive ANA test does not automatically mean you have lupus.
If you have several symptoms and a positive ANA test, further testing can be done to make a more definite diagnosis.
Antibodies to DNA (Anti-DNA antibody test)
Anti DNA antibodies are present in about 60-80% of individuals with active systemic lupus. This test is used to determine if there are antibodies to the genetic material in the cell (the protein that makes up the body's genetic code). The test is highly specific for systemic lupus and not found in individuals with other rheumatic diseases. It is also associated with a greater risk of lupus nephritis.
If the ANA test is positive, the tests for anti-Sm and anti-RNP are helpful in the diagnoses of various rheumatic diseases. These two tests are most helpful when ordered together.
Antibodies to the Sm antigen (Anti-Smith antibody) (Anti-Sm antibody)
Anti-Sm is present in about 30% of individuals with lupus. It is used to determine if there are antibodies to Sm, which are ribonucleoproteins found in the cell nucleus. This test is highly specific for systemic lupus and rarely found with other rheumatic diseases. It is often used to confirm a diagnosis of lupus.
Antibodies to RNP (ribonucleoprotein)
Anti RNP antibodies are found in many connective tissue diseases. Anti-RNP will be positive whenever anti-Sm is detected, but can be detected in some individuals with lupus in the absence of anti-Sm. When present in very high levels, RNP antibodies can suggest mixed connective tissue disease (MCTD), a condition with symptoms like those of systemic lupus.
Antibodies to Ro/SS-A (Anti-Ro (SSA)) and Antibodies to La/SS-B (Anti-La (SSB))
Anti-Ro is found in about 30% of individuals with systemic lupus and is also found with Sjögren’s syndrome. It is also associated with photosensitivity. Anti-La is found in about 15% of individuals with systemic lupus. Both of these are almost always found in babies who are born with neonatal lupus.
Antibodies to histones (DNA packaging proteins) are usually found in people with drug-induced lupus (DIL), but may also be found in those with systemic lupus.
Antibodies to Jo-1 are associated with polymyositis.
Antibodies to PM-Scl are associated with cases of polymyositis that also have features of scleroderma.
Antibodies to Scl-70 are found in people with a generalized form of scleroderma.
Antibodies to the centromere (a structure involved in cell division) are found in individuals with a limited form of scleroderma which tends to have a chronic course.
Antiphospholipid Antibodies
The most widely measured antiphospholipid antibodies are the lupus anticoagulant and the anticardiolipin antibody.
Anticardiolipin Antibody (ACA)
Measured in an ELISA (Enzyme-Linked Immunosorbent Assay) test. There are 3 classes of anticardiolipin that are usually tested: IgG, IgM and IgA. IgG is the most commonly detected, and is usually the most significant for lupus.
Lupus Anticoagulant (APL)
Present in about 30–40% of people with lupus. A positive APL plus the presence of arterial and venous thrombosis (blood clots) is called Antiphospholipid Antibody Syndrome, or APLS. APLS affects about 10–15% of individuals with lupus. This syndrome also occurs in individuals without lupus.
Complement
Serum (blood) complement is a group of blood proteins that cause immune responses and inflammation. Complement activity is measured to determine if complement is involved in the development of a number of diseases, including systemic lupus. It is also used to monitor the severity of a disease or to determine if medical treatment is working. There are nine major complement proteins, which are labeled C1 through C9. If the total blood complement level is low, or the C3 or C4 values are low and the person also has a positive ANA, some weight can be added to the diagnosis of lupus. These component levels may also be watched as an indicator of disease activity. Low C3 and C4 levels in people with a positive ANA may mean the presence of active disease, especially kidney involvement.
C-reactive protein (CRP) binding and erythrocyte sedimentation rate (ESR)
These levels frequently rise with generalized inflammation. The levels may increase in individuals with active lupus and decrease with corticosteroid or NSAID use.
Biopsy or tissue sample
Examination of tissue samples (biopsy) can further support the diagnosis of lupus and also helps to evaluate organ damage. The most common biopsy sites are the skin and kidney. The procedure involves removing a small amount of tissue, which is then examined under a microscope. The doctor can use the biopsy to identify the amount of inflammation and/or damage to the tissue.
Chemistry panel
Chemistry panels help determine a person’s general health status. They are also used to evaluate the body’s electrolyte balance and/or the status of body organs. In individuals with lupus, the tests may reveal muscle or kidney involvement or abnormalities of liver function. The Comprehensive Metabolic Panel (CMP) usually includes 14 tests and the Basic Metabolic Panel (BMP) usually contains 8 tests, all of which are found in the CMP.
Complete blood count (CBC)
Red blood count (RBC)
About 40% of individuals with systemic lupus will have a decrease in their RBCs (anemia), which may be caused by chronic inflammation, iron deficiency, GI bleeding, medications or autoantibody formation to RBCs.
White blood count (WBC)
About 15–20% of individuals with systemic lupus have a decrease in WBCs (leukopenia).
Platelets
About 25–35% of individuals with lupus have a low platelet count (thrombocytopenia).
Syphilis test (VDRL or RPR)
This test may be falsely positive in individuals with lupus.
Laboratory tests can also help determine if there is an increase in lupus activity.
An increase in lupus activity may cause the following blood test results to rise:
- CRP (C-reactive protein) binding
- ESR, or sedimentation rate
- Anti-DNA
- Liver and kidney function tests (AST, ALT, BUN, creatinine)
- CPK (if muscle involvement is present)
- Urine protein or cellular casts
An increase in lupus activity may cause the following blood test results to fall:
- CBC (red blood cell count, white blood cell count, platelets)
- Complement
- Serum albumin
What Does It All Mean?
Clinical laboratory tests can provide the doctor with a better picture of your health, and although the interpretation of tests and their relationship to symptoms can be difficult, the results of laboratory tests are important tools for doctors to use when making clinical decisions about your health, from diagnosis through therapy and prognosis. If you have signs and symptoms of lupus and your laboratory test results are abnormal, it is easier for physicians to make an accurate diagnosis and begin treatment.
Your doctor will interpret laboratory tests in the context of your entire evaluation. Sometimes laboratory tests need to be repeated to evaluate trends, which may provide more information than the measurement of a single test.
Every lab test has a normal range of values or reference ranges. The results of laboratory tests are compared to these reference ranges, which are established by measuring the laboratory results in a group of healthy individuals. Different laboratories have different standards and sometimes use a variety of substrates, therefore, the reference ranges for each laboratory test can differ between laboratories. If ongoing testing is being performed, try to have it performed at the same clinical laboratory. Be careful interpreting laboratory tests. On occasion, you may have a value for a laboratory test that falls outside the laboratory reference range, but the value may still be normal for you.
The results of laboratory tests may be influenced by medications or food. Always provide the doctor with information about any drug you are taking and inquire when you make an appointment whether you should fast before a lab test.
Clinical lab tests often provide the link between a vague set of symptoms (achy joints, fever, fatigue, or pain) and the doctor's early detection of disease and treatment. In short, lab tests can help save lives and improve quality of life.
If You Are Diagnosed With Lupus
For many individuals with lupus, following doctors' instructions very carefully is the first step in the right direction. While lupus can range from a mild inconvenience to a life-threatening disease, the good news is that, with the correct treatment(s) and a healthy lifestyle, many individuals with lupus can enjoy an improved quality of life. The more aware you are of lupus and its symptoms, the better equipped you will be to understand and cope with it. Life with lupus is often different and can be more challenging than life prior to lupus. But this doesn't mean you can't expect to go right on living life to the fullest.
There is a wealth of information available on the Internet and we encourage you to explore the following regarding laboratory testing and lupus.
Internet Resources
Learn about lupus treatments.
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