What is the appropriate treatment for a patient with a positive Lyme screen and negative Immunoglobulin G (IgG) and Immunoglobulin M (IgM) results?

Management of Positive Lyme Screen with Negative IgG and IgM Results

A positive Lyme screen with negative IgG and IgM Western blot results does not indicate active Lyme disease and does not require antibiotic treatment. 1

Understanding Two-Tiered Testing Results

The CDC recommends a two-tiered testing approach for Lyme disease diagnosis:

1. First-tier screening test: ELISA or indirect fluorescent antibody test
2. Second-tier confirmatory test: Western blot for IgG and IgM antibodies

When interpreting these results:

• A positive first-tier test requires confirmation with Western blot
• For IgM Western blot to be positive: ≥2 of 3 specific bands (21-24,39, and 41 kDa) must be present
• For IgG Western blot to be positive: ≥5 of 10 specific bands must be present 2

Clinical Decision Making

In this case:

• The screening test is positive
• Both IgG and IgM Western blots are negative
• This pattern represents a false-positive screening test 1

Key Points:

• Isolated positive screening tests without Western blot confirmation have poor specificity
• Cross-reactions with other bacterial antigens are common 3
• Overinterpreting a small number of antibody bands or a positive screening test alone leads to reduced specificity and potential misdiagnosis 2

Recommended Approach

1. Do not initiate antibiotic therapy based on a positive screening test with negative Western blot results 1

2. Reassess clinical presentation:

   • If erythema migrans rash is present in an endemic area, treat empirically regardless of serology 1
   • If no characteristic symptoms are present, consider alternative diagnoses

3. Consider follow-up testing only if:

   • Symptoms consistent with early Lyme disease develop
   • There is a known recent tick exposure with symptoms
   • Testing was performed very early (within first 1-2 weeks of infection) 2

Common Pitfalls to Avoid

• Overtreatment: Administering antibiotics based solely on positive screening tests leads to unnecessary antibiotic use and potential side effects 1

• Misinterpretation: Positive screening with negative confirmatory testing is not diagnostic of Lyme disease 2, 3

• Repeated testing: Without clinical changes, repeated testing increases the likelihood of false-positive results 1

• Extended antibiotic courses: Not supported by evidence and may lead to adverse effects 1

Special Considerations

• If clinical suspicion remains high despite negative serology, consider whether:
  • Testing was performed too early in the disease course
  • The patient has an erythema migrans rash in an endemic area (which allows clinical diagnosis)
  • Alternative diagnoses might explain the symptoms 1

Remember that serology as a single diagnostic tool has limited value and should only be used to support clinically suspected cases 3. The presence of nonspecific symptoms with a positive screening test but negative Western blot does not constitute evidence of active Lyme infection.