Diagnosis of lupus can be problematic. Making a correct diagnosis of lupus requires knowledge and awareness on the part of the doctor and good communication on the part of the patient.
An accurate medical history, physical examination and the results of laboratory tests help the doctor consider other diseases that may mimic lupus or determine if you truly have the disease.10
The most useful tests to aid a diagnosis identify certain autoantibodies often present in the blood of people with lupus. For example, the antinuclear antibody (ANA) test is commonly used to look for autoantibodies that react against components of the nucleus of the body's cells.
About 98% of people with lupus possess ANA, which can attack the nucleic material of your cells. However, there are a number of other causes of a positive ANA besides lupus, including infections and other autoimmune diseases.
Diagnostic tools for lupus include:
- Medical history
- Complete physical exam
- Laboratory tests including complete blood count (CBC), erythrocyte sedimentation rate (ESR), urinalysis, blood chemistries, complement levels, ANA and other autoantibody tests
- Skin biopsy
- Kidney biopsy.
Blood tests for lupus
Example of an ANA panel test.
In people with a positive ANA, more tests are usually performed to check for other antibodies that can help confirm a diagnosis.
Certain autoantibodies and substances in the blood can give information about which autoimmune disease, if any, is present. To check for other antibodies, doctors usually order an ANA panel, which checks for the following antibodies:17
- Anti-double-stranded DNA
1) Antiphospholipid antibodies (APLs)
APLs are a type of antibody directed against phospholipids. APLs are present in up to 60% of people with lupus.
A positive test is also used to help identify women with lupus that have certain risks that require preventive treatment and monitoring. Those risks include blood clots, miscarriage, or preterm birth.
2) Anti-double-stranded DNA antibody
The anti-double-stranded DNA antibody (anti-dsDNA) is a specific type of ANA antibody found in about 30% of people with lupus. The presence of anti-dsDNA antibodies often suggests a more serious form of lupus, such as lupus nephritis (kidney lupus).
3) Anti-Smith antibody
An antibody to Sm, a ribonucleoprotein found in the nucleus of a cell, is found 20% of people with lupus. Unlike anti-dsDNA, anti-Sm does not correlate with the presence of kidney lupus.
4) Anti-U1RNP antibody
Anti-U1RNP antibodies are commonly found along with anti-Sm antibodies in people with lupus. The incidence of anti-U1RNP antibodies in people with lupus is approximately 25%. Anti-U1RNP has been shown to be associated with features of scleroderma, including Raynaud's phenomenon. It has also been linked to other conditions, such as Jaccoud's arthropathy, a deformity of the hand caused by arthritis.
5) Anti-Ro/SSA and anti-La/SSB antibodies
Anti-Ro/SSA and anti-La/SSB are antibodies found mostly in people with lupus (30-40%) and primary Sjögren's syndrome. They are also commonly found in people with lupus who have tested negative for ANA.
Babies of mothers with anti-Ro and anti-La antibodies are at an increased risk of neonatal lupus, an uncommon condition that produces a temporary rash and can lead to congenital heart block. Therefore, women with lupus who wish to become pregnant should be tested for these antibodies.
6) Anti-histone antibodies
Antibodies to histones, proteins that help to lend structure to DNA, are usually found in people with drug-induced lupus, but they can also be found in people with SLE. However, they are not specific enough to lupus to be used to make a concrete diagnosis.
Serum (blood) complement test
A serum complement test measures the levels of proteins consumed during the inflammatory process. Low complement levels reflect that inflammation is taking place within the body. Variations in complement levels exist in different individuals simply due to genetic factors.
Some laboratories also include other antibodies in their panel, including antinucleoprotein or anticentromere.
Urine tests for lupus
Besides blood tests used to diagnose and monitor lupus, doctors use urine tests to diagnose and monitor the effects of lupus on the kidneys. These tests include the following:19
- Measurement of glomerular filtration rate and proteinuria: this test measures how effective the kidneys are at filtering the blood to eliminate waste products. It is conducted on urine collected over a 24-hour period
- Protein/creatinine ratio: this test is performed on a one-time urine sample. It measures for protein loss, an indicator of kidney function
- Urinalysis: urinalysis can be used in screening for kidney disease. The presence of protein, red blood cells, white blood cells and cellular casts may all indicate kidney disease.
Other laboratory tests are used to monitor the progress of the disease after diagnosis, and the effectiveness of medications include:18
- Erythrocyte sedimentation rate (ESR): a test that measures the amount of inflammation in your body
- C-reactive protein (CRP)/Westergren sedimentation rate: like the ESR, the CRP test measures inflammation. However, CRP usually changes more rapidly than ESR because it is made by the liver and secreted hours after the beginning of infection or inflammation
- Creatine phosphokinase (CPK): creatine is an enzyme (a protein that helps to elicit chemical changes in your body) found in your heart, brain, and skeletal muscles. When muscle tissue is damaged, CPK leaks into your blood. A high level of CPK usually indicates stress or injury to your heart or other muscles
- Coombs' test: the Coombs' test is used to detect antibodies that act against the surface of your red blood cells. The presence of these antibodies indicates a condition known as hemolytic anemia, in which your blood does not contain enough red blood cells because they are destroyed prematurely. An acquired form, autoimmune hemolytic anemia (AIHA), is present in about 10% of people with lupus and results from an immune system attack on your red blood cells.
X-rays and other imaging tests can help doctors see the organs affected by lupus.
A rheumatologist's diagnosis is considered the gold standard, with the American College of Rheumatology (ACR) using a standard classification scheme that requires 4 of 11 criteria for research definition. This system can sometimes fail to recognize or miss early and mild cases.
Classification of lupus
The 11 criteria for the diagnosis of lupus include:3,14
- Malar rash: butterfly-shaped rash across cheeks and nose
- Discoid rash: raised red patches
- Photosensitivity: skin rash as a result of unusual reaction to sunlight
- Oral or nose ulcers: usually painless
- Non-erosive arthritis (whereby the bones around joints do not get destroyed): involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion
- Pleuritis or pericarditis: inflammation of the lining around the heart (pericarditis) or lungs (pleuritis)
- Renal (kidney) disorder: excessive protein in the urine or cellular casts in the urine
- Neurologic disorder: seizures or psychosis/cognitive dysfunction
- Hematologic (blood) disorder: hemolytic anemia, low white blood cell count or low platelet count
- Immunologic disorder: antibodies to double-stranded DNA, antibodies to Sm, or antibodies to cardiolipin
- Positive ANA: positive test in the absence of drugs known to induce it.
There is frequent underdiagnosis of lupus due to the symptoms and signs not being specific. Equally, there is frequent overdiagnosis of the condition because doctors use a positive blood test (present in 5% of the healthy population) by itself to make a diagnosis.
On the next page we look at the treatment options for lupus and some of the measures that patients can take to cope with the disease.