Diagnosis with the CDC 2-step protocol

The diagnosis of Lyme disease is very complicated due to the interpretation of clinical symptoms and also the lack of reliable diagnostic testing. Similar to ME/CFS, the persistence of unexplainable symptoms for greater than 6 months in the absence of another alternative diagnosis may be indicative of chronic Lyme disease.

 
In 1994, the Centers for Disease Control & Prevention (CDC) published a two-step protocol for testing the presence of Lyme Disease.

CDC 2-step protocol

1. The first step uses an ELISA or IFA test. These tests are designed to be very "sensitive," meaning that almost everyone with Lyme disease, and some people who don't have Lyme disease, will test positive.  If the ELISA or IFA is negative, it is highly unlikely that the person has Lyme disease, and no further testing is recommended.  If the ELISA or IFA is positive or indeterminate (sometimes called "equivocal"), a second step should be performed to confirm the results.
2. The second step uses a Western blot test. Used appropriately, this test is designed to be "specific," meaning that it will usually be positive only if a person has been truly infected. If the Western blot is negative, it suggests that the first test was a false positive, which can occur for several reasons.  Sometimes two types of Western blot are performed, IgM and IgG. Patients who are positive by IgM but not IgG should have the test repeated a few weeks later if they remain ill. If they are still positive only by IgM and have been ill longer than one month, this is likely a false positive.