What tests should be ordered for Lyme disease serology in an inpatient?

Lyme Disease Serologic Testing for Inpatients

For inpatients with suspected Lyme disease, order a two-tiered serologic testing approach consisting of an enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA) as the first tier, followed by a Western immunoblot if the first tier is positive or equivocal. 1, 2

Two-Tiered Testing Protocol

First-Tier Test

• Order an EIA or IFA that detects both IgM and IgG antibodies against B. burgdorferi
• EIA is preferred over IFA as it is more easily automated and provides quantitative results 1
• Most laboratories use whole-cell sonicate preparations of B. burgdorferi, though newer tests using specific antigens like VlsE or C6 peptide are becoming available 1

Second-Tier Test (Reflexive)

• Only performed if first-tier test is positive or equivocal
• Western immunoblot for both IgM and IgG antibodies
• Interpretation criteria:
  • IgM is positive if ≥2 of 3 specific bands are present (21-24,39,41 kDa)
  • IgG is positive if ≥5 of 10 specific bands are present (18,21-24,28,30,39,41,45,58,66,93 kDa) 2

Special Considerations

For Suspected Neuroborreliosis

• Order serum antibody testing rather than PCR or culture of CSF or serum 1
• If CNS involvement is suspected, obtain simultaneous CSF and serum samples for determination of CSF:serum antibody index 1
• Do not order CSF serology without measurement of the CSF:serum antibody index 1

Timing Considerations

• Sensitivity of serologic testing is limited in early infection (first 2-4 weeks)
• Sensitivity increases with duration of infection:
  • Early localized disease: ~40% sensitivity in acute phase
  • Early disseminated disease: ~87-96% sensitivity
  • Late disseminated disease: nearly 100% sensitivity 1, 3

Common Pitfalls to Avoid

1. Do not skip the first-tier test - Western blot should never be ordered as a standalone test 2

2. Do not overinterpret Western blot bands - The presence of only 1 IgM band or fewer than 5 IgG bands does not indicate a positive result 2

3. Do not test patients with low pretest probability - Testing has poor positive predictive value in patients without:

   • Travel to or residence in endemic areas
   • Known tick exposure
   • Compatible clinical symptoms 2

4. Do not use unvalidated tests - Stick to FDA-cleared testing methods 1

5. Remember that antibodies persist - IgG antibodies can remain positive for years after treated infection, so positive serology alone doesn't indicate active infection 2

When Laboratory Testing Is Not Required

• Patients with classic erythema migrans (EM) in an endemic area can be diagnosed clinically without laboratory testing 2
• Treatment can begin immediately based on clinical diagnosis of EM 2

By following this evidence-based approach to Lyme serology testing for inpatients, you can maximize diagnostic accuracy while avoiding unnecessary testing and misinterpretation of results.