Lyme Serology Lab Lowdown
🔍 Case: An adult patient presents with flu-like symptoms — headache, fever/chills, muscle aches, and joint pain — following a recent trip to Vermont.
This presentation carries a broad differential, including a must-not-miss diagnosis of Lyme disease. Often elusive and variable in presentation, Lyme can be a tricky one to catch. I’m here to share practical tips to strengthen your confidence in assessing history, physical findings, recognition of erythema migrans, and key laboratory pearls.
First – some Quick, must-know facts about Lyme Disease:
What is Lyme disease? A tick-borne disease, caused by the spirochete bacterium Borrelia Burgdorferi.
Main transmission: infected black-legged ticks and western blacklegged ticks – typically need to be attached for at least 24 hours to transmit the bacteria. Disease prevalence is highest in Central Europe, Eastern Asia, Western Europe, and North America (1).
Black-legged tick: found in Canada (Manitoba, New Brunswick, Nova Scotia, Ontario and Quebec. In the US it is most common in the Northeast, Mid-Atlantic, and upper Midwest states (1,2).
Western blacklegged tick: found in coastal/southern BC, Canada BC, and the US – mainly pacific coast in California, Oregon, Washington; some found in Arizona, Utah, Nevada (1,2).
Exposures: many outdoor areas - parks, meadows, campgrounds, soccer fields; pets can carry ticks into the home, or they can stick to clothing (e.g. boots)
Recall the 3 stages of Lyme Disease
| Stage of Lyme Disease | Time Period (after infected tick bite) | Signs & Symptoms |
|---|---|---|
| Early Localized Lyme Disease | 3–30 days |
Flu-like symptoms: fever, malaise, myalgia, headache, migratory arthritis Lymphadenopathy Erythema migrans rash |
| Early Disseminated Lyme Disease | 1–3 months (infection may spread via bloodstream and lymphatic system) |
Vague symptoms: fatigue, general weakness Skin: multiple erythema migrans lesions Neurologic: aseptic meningitis (fever, severe headache, nuchal rigidity), cranial neuropathy (Bell’s palsy), encephalitis (rare), subtle cognitive changes, motor or sensory deficits (numbness, limb pain) Cardiac (~5% of cases): Lyme carditis (AV block, arrhythmia, myocarditis) Other rare findings: conjunctivitis, keratitis, uveitis, splenomegaly, mild hepatitis |
| Late Disseminated Lyme Disease | >3 months (delayed diagnosis or untreated disease) |
Musculoskeletal: joint pain and/or swelling (mono- or polyarticular, commonly knees and large joints) Neurologic: meningitis, meningoencephalitis, subacute/mild encephalopathy (memory or concentration issues), neuropathy (shooting pain in distal extremities) |
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Erythema Migrans Rash - Clues on History & Physical Exam
Typical features:
Appears 3–30 days after a tick bite (usually ~7 days).
>5 cm, painless, non-itchy, and expanding over ≥48 hours.
Can persist for weeks if untreated.
Common sites: axilla, groin, popliteal fossa — always perform a full skin exam.
Rash on darker skin tones, may look bruise-like rather than red (1,3,4)
💡 If rash <5 cm and appeared within 48 hours, trace its border and reassess — expansion beyond the outline suggests EM (3).
Not all EM rashes are bull’s-eye! Can appear as:
Expanding red or bluish lesion (± central clearing)
Red oval plaque
Lesion with central crust
Multiple rashes → possible disseminated infection (1,3,4)
🔎 Back to the case: symptoms have been present for 5 days, there are no known sick contacts, and he went on several hikes in Vermont. He has no cough, rhinorrhea, or sore throat. No high risk sexual activity. He denies any known tick bites. There is no lymphadenopathy or rash on exam. What next? When should we consider Lyme Serology?
BOTTOM LINE: Erythema migrans rash is typically >5 cm, painless, and non-itchy, with progressive expansion over 48 hours or more.
Lyme Disease Lab Testing
If you’re thinking of ordering Lyme Disease testing, consider the following:
Assess Exposure Risk: High risk = known tick bite attached >24 h, or exposure in a Lyme-endemic area (e.g. hiking, camping, parks, meadows, golf/soccer fields).
If EM rash present: Clinical diagnosis — no lab confirmation needed. Begin treatment immediately (1)
If NO rash but known tick bite + symptoms suggestive of Lyme disease
Common symptoms: headache, fever, myalgias, arthralgias.
Order two-tier serologic testing (EIA → Western blot).
Do not delay treatment if pre-test probability is high (3)
If no known tick bite but exposure risk & symptoms suggestive of Lyme disease: Two reasonable approaches (unvalidated, Center for Effective Practice guidance):
A. Treat empirically → early therapy, prevents progression; but risk of overtreatment/antibiotic resistance.
B. Watch & wait → test and treat if positive; avoids overtreatment but delays care and may worsen morbidity.
Testing overview
Tier 1: EIA/ELISA for B. burgdorferi antibodies (~1-week turnaround).
If positive/equivocal: Tier 2 Western blot or confirmatory EIA.
If negative results and tested early (<30 days since symptom onset): repeat in 4–6 weeks; don’t retest again if persistently negative.
Diagnosis: requires IgM positivity if symptoms <1 month, and IgG positivity if symptoms >1 month - IgM alone is unreliable beyond 30 days (risk of false positive results).
If negative but suspicion remains → consider alternative diagnosis or ID consult (1,3)
💡 Practical tip: On lab requisition, document exposure location (province/state/country) and symptom duration (>1 month → IgG positivity needed for diagnosis). European testing also differs as they have different bacteria that cause Lyme disease.
Skin biopsy: rarely helpful; may show borrelial lymphocytoma or acrodermatitis chronica atrophicans — not diagnostic.
Reporting: All laboratory-confirmed or clinically diagnosed Lyme cases are reportable to public health.
🔎 Back to the case: First-tier testing is positive, and second-tier testing confirms positive IgM antibodies to B. Burgdorferi – which fits the clinical picture of symptoms <1 month. Most likely diagnosis: early localized Lyme Disease.
Note: depending on pre-test probability, and risk/benefit discussion with the patient, treating with antibiotics is an option while waiting for test results – it all depends on the clinical scenario.
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References
Government of Canada. 2025. Lyme Disease: For health professionals. Available from https://www.canada.ca/en/public-health/services/diseases/lyme-disease/health-professionals-lyme-disease.html
Centers for Disease Control and Prevention. 2025. Lyme Disease Surveillance and Data. Available from https://www.cdc.gov/lyme/data-research/facts-stats/index.html
Center for Effective Practice. 2020. Early Lyme Disease Management in Primary Care Tool (English). Available from https://cep.health/clinical-products/early-lyme-disease/
Centers for Disease Control. 2024. Lyme Disease Rashes. Available from https://www.cdc.gov/lyme/signs-symptoms/lyme-disease-rashes.html