Diagnosis can be made from a characteristic clinical picture, but not all patients present with a classic erythema migrans lesion. Shown below are a few example images of atypical lesions.
Figures 12, 13, 14, and 15 depict a characteristic red, expanding rash called erythema migrans (EM) caused by the bacterium Borrelia burgdorferi. B. burgdorferi bacteria are transmitted to humans through the bite of infected blacklegged ticks.A serological testing approach is used to obtain a laboratory diagnosis. The CDC recommends a two-step testing procedure, as outlined in the top image on the right. 60 to 70% of enzyme immunoassay (EIA), enzyme-linked immunosorbent assay (ELISA), or immunofluorescence assay (IFA) tests are positive by week four. For this reason, an EIA (rarely IFA) is performed as the first step. If the EIA/IFA is positive or equivocal (indeterminate), the CDC recommends that an immunoblot (commonly a Western blot) test be performed as the second step.
If the patient has had symptoms ≤30 days, perform both the IgM and IgG Western blots (WB). If the patient has had symptoms ≥30 days, just perform the IgG WB. When interpreting the IgG WB, it is required that at least five IgG bands are detectable.
On July 19, 2019, the Food and Drug Administration (FDA) approved a modified version of the two-test methodology. This new modified methodology can use a second EIA in place of a Western blot test.
Numerous infections and conditions may cause false-positive EIA/ELISA tests, thus the need for a confirmatory WB. Some of the more common false-positive results are seen in:
- Tick-borne relapsing fever
- Syphilis
- Anaplasmosis
- Leptospirosis
- Some autoimmune disorders (e.g., lupus)
- Bacterial endocarditis
- Infection with Helicobacter pylori, Epstein Barr virus, or Treponema denticola (bacteria found in the mouth that can cause gum disease and/or infection after dental procedures)
The ELISA test is very sensitive, so if it is negative, go no further unless symptoms persist. Then, repeat the ELISA or IFA at a later time. Cultures can be performed, but the yield is low (only about 27% in one study). Polymerase chain reaction (PCR) is also not very sensitive (positive about 50% of the time). This is primarily because choosing the specimen most likely to yield a positive test is difficult.
There are limitations to testing. For one thing, there is no FDA-approved rapid test, nor is there an antigen test available. The decay of antibodies is unpredictable; therefore, you cannot determine if a positive test result is a new infection or a previous one. Furthermore, there is no test to determine if the patient is cured.
Several laboratory-developed tests have come under scrutiny. The CDC has issued warnings against many of these because they can be inaccurate.
Figure 12. Centers for Disease Control and Prevention. (n.d.). This image depicts the posterior knee, or popliteal region of a patient’s right leg who had presented with an erythema migrans (EM) rash, characteristic of what was diagnosed as Lyme disease, caused by the bacterium, Borrelia burgdorferi.B. burgdorferi bacteria are transmitted to humans through the bite of infected blacklegged ticks. [Image]. https://phil.cdc.gov/Details.aspx?pid=14478.
Figure 13. Centers for Disease Control and Prevention. (n.d.). This photograph depicts the medial aspect of the right calf of a patient, who had presented with what was diagnosed as Lyme disease. Note the characteristic red, expanding rash referred to as erythema migrans (EM), that had been caused by the bacterium, Borrelia burgdorferi. In the background, you can also see that the patient’s right leg, also displayed an EM rash.B. burgdorferi bacteria are transmitted to humans through the bite of infected blacklegged ticks. [Image]. https://phil.cdc.gov/Details.aspx?pid=14475.
Figure 14. Centers for Disease Control and Prevention. (n.d.). This image depicts the lateral aspect of the left thigh of a patient who had presented with what was diagnosed as Lyme disease. Note the characteristic red, expanding rash called erythema migrans (EM), that had been caused by the bacterium, Borrelia burgdorferi.B. burgdorferi bacteria are transmitted to humans through the bite of infected blacklegged ticks. [Image]. https://phil.cdc.gov/Details.aspx?pid=14470.
Figure 15. Centers for Disease Control and Prevention. (n.d.). This image depicts the lateral aspect of the left thigh of a patient who had presented with what was diagnosed as Lyme disease. Note the characteristic red, expanding rash called erythema migrans (EM), that had been caused by the bacterium, Borrelia burgdorferi.B. burgdorferi bacteria are transmitted to humans through the bite of infected blacklegged ticks. [Image]. https://phil.cdc.gov/Details.aspx?pid=14471.
Figure 16. Association of Public Health Laboratories. (2024). Standard two-tiered testing. [Image]. https://www.aphl.org/aboutAPHL/publications/Documents/ID-2024-Lyme-Disease-Serologic-Testing-Reporting.pdf.
