Diagnosis:

Proper diagnosis of Lyme disease is important. A diagnosis of Lyme disease is straightforward if the patient meets the following criteria:

• Lives in an area of tick-infestation
• Has the tell-tale bulls-eye rash
• Has other symptoms (headache, joint aches, malaise, flu-like symptoms)

If the patient meets all the criteria, except the rash, the doctor may undertake the enzyme-linked immunosorbent assay (ELISA) or the Western Blot test.

Culture

In a few cases, if the patient seeks a diagnosis within the first 2 - 3 weeks, the doctor may take a sample of the skin or of the blood. If Lyme spirochete is present, it may be identified in the laboratory in a culture medium (a substance in which the organism can thrive and reproduce). This is necessary only if a doctor suspects Lyme but the diagnosis is not clear.

Immune Testing

If the infection is not obvious from the patient's history and physical symptoms, but Lyme disease is suspected, the doctor may run tests for evidence of specific factors that suggest infection with B. burgdorferi. Such factors include:

• Proteins referred to as Osps. These proteins (referred to as Osp A through F) coat the outer surface of the B. burgdorferi spirochete and then attach to human cells after infection.
• Antibodies that attack these Osps. Antibodies are the weapons of the immune system that are launched when foreign invaders (called antigens) are detected. In the case of Lyme disease, these antigens are the Osps.

Specific Tests.

The U.S. Centers for Disease Control (CDC) recommends a two-step process for Lyme disease blood tests:

• ELISA and Other Initial Tests. The first tests used are either enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test. ELISA is the immune test used most often for Lyme disease. (The IFA test is less accurate but may be used when ELISA isn't available.) ELISA measures antibodies that are directed against the B. burgdorferi spirochete. A newer variant is a rapid test (PreVue) that can provide results within an hour. Positive results from any of these tests still require confirmation with a Western blot test. Negative results do not require further testing.
• Western Blot. If any of these tests is positive or uncertain, they are followed by the Western immunoblot (WB). This test is more accurate and is very helpful in confirming the diagnosis. The Western blot creates a visual graph showing bands of different colors or shading that laboratories use to interpret the immune response.

The CDC recommends only these tests. Other tests -- such as urine antigen, immunofluroescent staining, and lymphocyte transformation -- do not have enough scientific evidence to support their use.

Accuracy of the Tests. These tests are very expensive, and none are completely accurate in either identifying Lyme or ruling it out. They should never be used to make a primary diagnosis of Lyme disease in patients who do not have obvious symptoms of the disease.

Both false positive and false negative results are common with these tests.

False positive results occur when the test suggests the presence of the disease, but the person does not actually have an active infection. This may occur in different ways:

• The antibodies to the infectious organism triggering the antibodies are not the Lyme spirochetes. Other organisms that can trigger such antibodies include syphilis and relapsing fever. Dental infections may trigger a false positive response.
• The patient may have been infected with Lyme disease previously and harbor antibodies to the disease.

False negative results miss the actual presence of the disease. These results are also common. (If the results are negative but Lyme disease is highly suspected, the doctor will probably prescribe antibiotics anyway.) False negative results occur for a number of reasons:

• The test is taken too early in the course of Lyme disease. In such cases, the antibodies that fight the spirochete might not have reached a level that is high enough to be detected. (Only about 20 - 30% of patients can be identified using immune system tests in the first 2 - 4 weeks. By the fourth week, up to 80% of patients will have detectable antibodies.)
• The patient has taken certain medications, such as steroids or certain anti-cancer drugs, which reduce the immune system's ability to produce antibodies, including those in response to Lyme disease.
• There are too many infection-fighting antibodies attached to the bacteria. In this case, there are not enough loose antibodies in the blood sample to trigger a response.
• The laboratory itself has set its sensitivity point too high. Some laboratories establish a standard of very high antibody levels before the test results will trigger a finding of Lyme disease. (They do this to avoid too many false-positive responses.) In so doing, however, their tests may miss the disease in patients with lower antibody levels. A related diagnostic problem concerns the possibility of missing persistent Lyme disease after antibiotic treatments, when antibody levels would be low.

All of this means that a negative blood test does not rule out a diagnosis of Lyme disease, particularly if symptoms strongly suggest its presence. Conversely, a positive blood test does not prove that Lyme disease is causing the symptoms. A second blood test, taken several weeks later, may help.

Polymerase Chain Reaction (PCR) Test

The polymerase chain reaction (PCR) test detects the DNA of the bacteria that causes Lyme disease. However, it requires technical expertise and expensive equipment, and can be performed only in a few laboratories in the country. The test also has a high risk of false-positive results. Research indicates that blood or urine samples do not provide accurate results, but skin biopsies may be useful in some cases. At this point, the PCR test is reserved for certain patients with specific diagnostic problems. For most patients, standard antibody tests are preferred.

Tests for Neurologic Involvement

Analysis of Spinal Fluid. In patients who have neurologic symptoms, a lumbar puncture (a spinal tap) may be used to test for the bacteria in spinal fluid and may be useful for an early diagnosis of Lyme disease.