Diagnosis:

No single test can confirm or rule out SLE. A number of tests are required before SLE can be diagnosed definitively. The first symptoms of SLE can resemble one of many syndromes or disorders, including rheumatoid arthritis, Still's disease, rheumatic fever, Lyme disease, multiple sclerosis, thrombotic thrombocytopenia purpura, cryoglobulinemia, Weber-Christian disease, viral infections, vasculitis, psychosis, and other conditions. Other autoimmune disorders, such as Sjögren syndrome or scleroderma, may even be present at the same time as SLE.

Tests for Autoantibodies

Methods for measuring the antibodies involved with SLE vary, and the range of results can be bewildering. Repeat tests may be needed.

Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus.

High levels of ANA are found in more than 98% of patients with SLE. Other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:

• Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren syndrome, or rheumatoid arthritis).
• They also may be weakly present in about 20 - 40% of healthy women.
• Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.

A negative ANA test makes a diagnosis of SLE unlikely but not impossible. High or low concentrations of ANA also do not necessarily indicate the severity of the disease, since antibodies tend to come and go in patients with SLE.

In general, the ANA test is considered a screening test:

• If SLE-like symptoms are present and the ANA test is positive, other tests for SLE will be administered.
• If SLE-like symptoms are not present and the test is positive, the doctor will look for other causes, or the results will be ignored if the patient is feeling healthy.

ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.

• Anti-double stranded DNA (Anti-ds DNA) is more likely to be found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE, and high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
• Anti-Sm antibodies are also usually found only with SLE. Levels are more constant and are more likely to be detected in African-American patients. Although many lupus patients may not have this antibody, its presence almost always indicates SLE.
• When the ANA is negative but the diagnosis is still strongly suspected, a test for anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB) antibodies may identify patients with a rare condition called ANA negative, Ro lupus. These autoantibodies may be involved in the sun-sensitive rashes experienced by patients with SLE and are also found in association with neonatal lupus syndrome, in which a pregnant mother's antibodies cross the placenta and cause inflammation in the developing child's skin or heart.

Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The test accurately detects lupus in 50 - 70% of patients who test positive for these antibodies.

Antiphospholipid Antibodies. In patients with SLE in whom blood abnormalities are suspected, tests may be able to detect the presence of the two major antiphospholipid antibodies:

• A quarter to a half of patients with SLE may have these antibodies. Antiphospholipid antibodies increase the risks for blood clots and may be responsible for narrowing of (and irregularities in) blood vessels. Antiphospholipid antibodies are linked with miscarriages and other pregnancy complications, strokes, heart attacks and blood clots in almost any part of the body, including kidneys, legs, lungs, and eyes.
• The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for clotting in the body and, therefore, the presence of lupus anticoagulant.
• An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.

As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.

Miscellaneous Blood Tests

Complement. Blood tests of patients with SLE often show low levels of serum complement, a protein in the blood that aids the body's infection fighters. Individual proteins are termed by the letter "C" followed by a number. Common complement tests measure C3, C4, C1q, and CH50. Complement levels are especially low if there is kidney involvement or other disease activity.

LE Cell Tests. The first blood test ever used for SLE called LE (lupus erythematosus) cell test is positive in only about half of patients with SLE and is no longer used that often.

Blood Count. White and red blood cell and platelet counts are usually lower than normal and, depending on severity, are used to determine complications, such as anemia or infection.

Skin Tests

If a skin rash is present, the doctor may take a biopsy (a tissue sample) from the margin of a skin lesion. A test known as a lupus band detects antibodies known as immunoglobulin G (IgG), which are located just below the outer layer of the tissue sample. They are much more likely to be present with active SLE then with inactive disease. The biopsy will not differentiate between systemic and discoid lupus, but it can rule out other diseases. Tests for other antibodies will rule out or confirm discoid lupus and subacute cutaneous lupus.

Tests for Serious Complications of SLE

Kidney Damage and Lupus Nephritis. Kidney damage in patients already diagnosed with SLE may be detected from the following tests:

• Blood tests that measure creatinine, a protein metabolized in muscles and excreted in the urine. High levels suggest kidney damage, although kidney problems can also be present with normal creatinine levels.
• Tests for detecting anti-ds DNA antibodies and complements.
• A kidney biopsy. This may be performed to determine if lupus nephritis is present when less invasive tests indicate kidney involvement. It is not absolutely accurate but it helps determine treatment. Electron microscopy (very high-powered electronic microscopes) may be especially important in obtaining critical information on the degree of kidney damage.

Lung and Heart Involvement. A chest x-ray may be performed to check lung and heart function. An electrocardiogram and an echocardiogram are administered if heart disease is suspected.

Central Nervous System Complications. SLE occurring in the central nervous system (CNS) can be difficult to diagnose because its symptoms are easily confused with other psychiatric and neurologic conditions.

• Tests of the cerebrospinal fluid (CSF) for elevated levels of autoantibodies are the most reliable ways to detect CNS complications caused by a faulty immune system.
• Additional tests, including electroencephalograms (EEGs), magnetic resonance imaging (MRI), computed tomography (CT), or x-rays may be useful when blood vessel blockage in the brain is suspected.
• If the doctor suspects that CNS symptoms are caused by infection, especially for patients who are receiving immunosuppressant therapy, a lumbar puncture should be performed.

Osteoporosis. To detect early osteoporosis in patients with SLE whose disease has lasted more than 3.5 years, doctors recommend an imaging test called dual energy x-ray absorptiometry (DEXA) to measure bone mineral density.