by Brian Schwartz, M.D., M.S.
The diagnosis of Lyme disease is clinical, and the diagnostician must consider many types of evidence. The history is very important to the diagnosis of the disease (e.g., opportunity for tick exposure? live or work in endemic area? recent tick bites?). The temporality and pattern of the development of symptoms is critical to the diagnosis. Many patients have access to scientific and lay publications on Lyme disease, and use a “check list” approach to self-diagnosis, by circling the several symptoms that they have experienced off the list of 50 symptoms that have been attributed by some authors to Lyme disease. A detailed description of the rash may be helpful if it is not present at the time of the examination. The history that the rash expanded over several days, eventually surpassing 5 cm in diameter, is a useful clue.
Classical later presentations such as unilateral facial palsy, heart block, or frank monoarticular arthritis of the knee, should motivate the physician to obtain appropriate diagnostic tests for Lyme disease and to exclude other causes. Diagnosis of Lyme disease is aided by serologic testing, which should include antibody testing by ELISA, and if positive, follow-up with Western blot testing for both immunoglobulin G and M antibodies. By 6-8 weeks of infection, most patients will have an appropriate antibody response. The sensitivity of serologic testing is approximately 50% at the erythema migrans stage, but increases to over 90% by the later stages of the disease. Serologic testing is thus not very helpful in a patient with classic erythema migrans, who will be treated for Lyme disease regardless of the serologic test result. The specificity of serologic testing is approximately 90-95% for all stages of the disease.
As recommended by the Centers for Disease Control, a positive ELISA test result must be followed by Western blot testing. The usual criterion for a positive Western blot for IgM is at least two bands corresponding to proteins of specific molecular weights (two of the following three: 23, 39, or 41 kDa). For Western blot testing for IgG, the usual criterion is five bands corresponding to proteins of specific molecular weights (five of the following ten: 18, 23, 28, 30, 39, 41, 45, 58, 66, or 93 kDa). Most laboratory test reports of Western blots will include the molecular weights of the important proteins in the report, both of the criterion proteins and the proteins to which the patient has produced antibodies. It is important to note that in patients with symptoms present for at least one month, a positive IgM test alone is insufficient evidence of infection and is more likely to be a false positive, rather than true positive, result. This is likely due, at least in part, to the less stringent criterion for a positive IgM Western blot (only two positive bands). Even though both IgG and IgM antibodies are evaluated by the Western blots, these results do not clearly distinguish between active and past infections. Test results can remain positive for years, and studies have documented that asymptomatic serconversion can occur.
Other diagnostic testing modalities are available. These include polymerase chain reaction (PCR) testing of blood, skin biopsy samples, cerebrospinal fluid, joint fluid, or urine. Some laboratories are selling a Lyme urinary antigen test. At this time, these tests must all be considered to be research tools and are generally of limited clinical utility. PCR testing of blood or urine seems to have no clinical utility and is not recommended. PCR testing of joint fluid may be a useful adjunct to diagnosis, when performed in laboratories with careful control of possible exogenous contamination. PCR testing of cerebrospinal fluid seems to be less sensitive and is not routinely recommended.
In the patient with numerous nonspecific symptoms that may or may not be compatible with Lyme disease, the clinician must understand that if the pretest probability of Lyme disease is low, a positive serologic test result is more likely to be false positive than it is to be true positive. Lyme disease serologic testing should be used with caution in patients complaining solely of nonspecific symptoms such as, for example, chronic fatigue, headaches, or diffuse musculoskeletal pain.