Lyme Disease

Lyme disease is caused by the spirochete Borrelia burgdorferi, transmitted through the bite of an infected Ixodes (blacklegged) tick — Ixodes scapularis in most of Canada and the eastern/central United States, Ixodes pacificus on the Pacific coast. Transmission requires prolonged tick attachment, since the spirochete must migrate from the tick's gut to its salivary glands during feeding; risk rises sharply the longer an infected tick remains attached.^[1] Left untreated, infection can progress from a localized skin infection at the bite site to disseminated disease affecting the nervous system, heart, and joints — but Lyme disease is highly treatable at every stage with the correct antibiotic and duration, and most patients recover fully once appropriately treated.^[2]

Classic erythema migrans with central clearing at a tick-bite site. (CDC/James Gathany, Public Health Image Library #9875, public domain)

Erythema migrans (the presenting sign in most cases)

Appears at the site of the tick bite — commonly the groin, axilla, waist, back, or legs in adults, and the head or neck in children — and enlarges over days to reach a diameter of at least 5 cm. Morphology varies: many lesions are a uniform erythematous plaque, some show the classic "bull's-eye" appearance with central clearing, and others blister, become necrotic, or take on a bruise-like blue or purple hue. The lesion is non-tender and has well-defined margins; it may be pruritic or produce a stinging sensation. It can be accompanied by flu-like symptoms — fatigue, headache, myalgia, arthralgia, or low-grade fever.^[1]

• Outdoor activity — hiking, camping, gardening, hunting, or working — in wooded, brushy, or tall-grass areas, including backyards and playgrounds, not only remote wilderness.
• Residence in or travel to an established or expanding tick-endemic area of Canada — current risk areas include parts of southern and eastern Ontario, southern Quebec, Nova Scotia, New Brunswick, southeastern Manitoba, and southern British Columbia; risk-area boundaries continue to expand, so exposure cannot be excluded on geography alone outside these zones.^[2]
• Highest activity for ticks (and therefore highest transmission risk) is spring through fall.
• Prolonged, unrecognized tick attachment — many patients never notice or recall the bite.
• Not using tick repellent or protective clothing when in tick habitat, or skipping a post-outdoor-activity tick check.
• Outdoor pets that are not checked for ticks before coming indoors.

Differentiating erythema migrans from its common mimics

History

• Ask specifically about outdoor activity and exposure to wooded, brushy, or tall-grass environments — including gardens and residential yards — in or near an established or expanding Canadian risk area, and about travel to other endemic regions.
• A remembered tick bite is not required for diagnosis — many patients are unaware they were bitten.
• Characterize the timeline and morphology of any skin lesion(s), and ask about systemic symptoms (fever, fatigue, myalgia, arthralgia), neurologic symptoms (facial droop, headache, neck pain, paresthesias), and cardiac symptoms (palpitations, dizziness, syncope, dyspnea).

When a typical erythema migrans lesion needs no testing

Two-tier serologic testing — for atypical presentations, or disseminated/late disease

Use two-tier testing when the presentation is atypical, or when evaluating for early disseminated, neurologic, cardiac, or late (arthritis) disease: (1) a screening enzyme immunoassay (EIA), followed by (2) a confirmatory immunoblot (IB) only if the EIA is equivocal or positive. Do not order the immunoblot as a standalone first test — it must follow a positive or equivocal screening EIA. Sensitivity of the 2-tier assay is substantially higher in early disseminated, neurologic, or cardiac disease than in early localized disease, and highest in late-stage disease. If suspicion for early disseminated, neurologic, or cardiac Lyme disease remains high despite an initial negative test, repeat serology in 2-4 weeks.^[2]

• Testing must be performed at an approved Canadian laboratory — reliability at unvalidated labs has not been established.
• Note any presumed European exposure explicitly on the requisition — European Lyme disease is caused by different Borrelia species (B. afzelii, B. garinii) and needs an alternative serologic panel to be detected.
• Do not use serology as a test of cure or to monitor treatment response — antibodies can persist for years after successful treatment and do not distinguish active from past infection.

Other investigations, and when they are not indicated

• Lumbar puncture: indicated for suspected meningitis, or unilateral facial nerve palsy accompanied by delirium, fever, or a severe/prolonged headache. Measure opening pressure. Expect lymphocytic pleocytosis with normal protein and glucose; PCR on CSF has very low sensitivity and should not be ordered routinely.
• Synovial fluid analysis: mainly used to exclude septic arthritis when the diagnosis is uncertain — cell counts alone do not reliably discriminate Lyme arthritis from septic arthritis. PCR for B. burgdorferi DNA can support the diagnosis but should not be used as a stand-alone test, and may remain positive after successful treatment.
• ECG: only for patients with symptoms of carditis (dyspnea, syncope, palpitations, chest pain) — not indicated routinely in asymptomatic early Lyme disease.
• Routine bloodwork (CBC, electrolytes): nonspecific and usually normal in Lyme disease; not useful for diagnosis.

Co-infection with other tick-borne pathogens

The same Ixodes ticks can transmit other pathogens whose presentations overlap with Lyme disease; consider co-infection in a patient with unexplained thrombocytopenia, hemolytic features, or more severe systemic illness than expected. Anaplasmosis (Anaplasma phagocytophilum) typically presents as an acute, nonspecific febrile illness with myalgia, malaise, headache, and cough, without a rash; laboratory features include thrombocytopenia, leukopenia, mild anemia, and elevated liver enzymes, diagnosed by PCR/NAAT early or serology later. Babesiosis (Babesia microti) presents as a nonspecific febrile illness with fatigue, chills, and headache, also without a rash; laboratory features include anemia, thrombocytopenia, and hepatitis, confirmed by intraerythrocytic parasites on blood smear or PCR. Borrelia miyamotoi, an Ehrlichia muris-like organism, and Powassan virus are additional possible co-infections to consider in an atypical or refractory presentation with the same geographic exposure.^[1]

• Recognize and treat early localized disease (erythema migrans) promptly to prevent dissemination.
• Match the antibiotic agent, route, and duration to the specific clinical stage/manifestation — localized skin, neurologic, cardiac, or articular.
• Prevent Lyme disease after a genuinely high-risk tick bite using single-dose postexposure prophylaxis when criteria are met.
• Fully resolve neurologic, cardiac, and articular manifestations of disseminated or late disease.
• Avoid unnecessary prolonged or repeated antibiotic courses for symptoms not attributable to active infection.

Tick bite prevention

• Wear light-coloured, long-sleeved clothing in tick habitat to make ticks easier to spot.
• Shower or bathe within 2 hours of being outdoors, paying particular attention to the armpits, groin, back, and scalp — this helps dislodge unattached ticks before they bite.
• Do a full-body tick check daily on yourself and on children, especially the hairline, underarms, navel, and groin.

Tick removal technique — a real pharmacist counselling point

Insect repellents

In the absence of a licensed human vaccine, avoiding tick bites is the mainstay of prevention. Health Canada's age-based recommendations for the 2 preferred repellent active ingredients:^[5]

Icaridin is odourless, does not feel sticky, and does not damage synthetic fabrics or plastics — a practical reason to recommend it over DEET for a child who will be wearing repellent repeatedly.

After a tick bite that does not meet postexposure prophylaxis criteria

• Counsel the patient to monitor the bite site and their overall health for up to 1 month for an expanding rash or flu-like symptoms, and to seek care promptly if either develops.
• Explain that prior infection does not provide protective immunity — reinfection with Lyme disease has been well documented, so the same prevention counselling applies regardless of past infection.

Breastfeeding: there is no evidence of transmission via breastfeeding. Follow the same drug preference as in pregnancy — amoxicillin or cefuroxime axetil for treatment, ceftriaxone for severe disease — and apply the same individualized discussion before using doxycycline for postexposure prophylaxis.

Pediatrics

Doxycycline is now first-line for children of any age provided the course is ≤21 days — current evidence does not support withholding it under age 8 for short courses, superseding older teaching.^[7] Use weight-based dosing throughout (see Pharmacologic Treatment Options and Drug Tables). In children under 8 with a high-risk tick bite meeting all 3 postexposure prophylaxis criteria, the benefit of a single dose of doxycycline generally outweighs the risk. Amoxicillin has not been studied for single-dose prophylaxis and should not be used for that indication in any age group; azithromycin is reserved for the same narrow 2nd-line role as in adults.

Renal and hepatic impairment

Penicillin G and cefotaxime are renally cleared and require dose reduction in significant renal impairment — consult a renal dosing reference for the adjusted regimen. Ceftriaxone does not require dose adjustment for renal impairment alone given its predominant biliary excretion, but use caution with combined significant hepatic and renal impairment. Review doxycycline, amoxicillin, and cefuroxime axetil dosing in significant renal impairment; doxycycline itself does not require adjustment for renal impairment alone.

Confirm clinical resolution rather than relying on repeat serology — antibodies persist for years after successful treatment and are not a test of cure. For erythema migrans, confirm the lesion resolves and watch for any new systemic or neurologic/cardiac symptoms during and after treatment, which would indicate dissemination rather than treatment failure. For facial nerve palsy, follow recovery clinically; antibiotics prevent late complications but do not accelerate the palsy's own resolution, and ophthalmology involvement may be needed for eye protection if closure is incomplete. For carditis, continue cardiac monitoring while hospitalized with PR prolongation — third-degree block typically resolves within 1 week of starting treatment, and lesser degrees of block within up to 6 weeks — then arrange outpatient ECG follow-up until resolution is confirmed.^[3] For arthritis, some residual joint swelling can persist for weeks after an otherwise successful course; adjunctive NSAIDs may help symptoms while awaiting resolution. Watch for a Jarisch-Herxheimer-like reaction (fever, chills, rigors, sweating, myalgia, arthralgia) within 24 hours of starting treatment — this is a benign, self-limited reaction to spirochete lysis lasting under 48 hours, manageable with NSAIDs, and is not a sign of drug allergy or treatment failure.

1. Confirm the original diagnosis was accurate — a genuinely typical EM lesion with plausible exposure, or a correctly performed 2-tier serology — rather than assuming the antibiotic has failed.
2. Confirm the correct drug, dose, and full prescribed duration was completed for the specific stage being treated.
3. For recurrent symptoms after treatment of early localized disease, consider reinfection from a new tick bite before assuming relapse of the original infection — prior infection does not confer protective immunity.
4. For Lyme arthritis with only mild residual swelling after the initial oral course, a second 28-day oral course is a reasonable next step.
5. For Lyme arthritis that fails to resolve or relapses after oral therapy, move to IV ceftriaxone (or cefotaxime) for 14-28 days.
6. For synovitis persisting 2 months or more after an adequate course of IV ceftriaxone (or after 2 completed oral courses), this is antibiotic-refractory Lyme arthritis — refer to rheumatology; further antibiotics are not indicated, and management shifts to anti-inflammatory therapy.
7. For persistent nonspecific symptoms (fatigue, musculoskeletal pain, or difficulty with concentration/short-term memory) more than 6 months after an appropriately completed treatment course, this is post-treatment Lyme disease syndrome — do not prescribe a prolonged or repeated antibiotic course. Randomized trial evidence shows no benefit from extended antibiotics for this syndrome, along with real risk of serious adverse effects, and AMMI Canada does not support prolonged antimicrobial therapy for persistent symptoms attributed to Lyme disease. Manage supportively, targeting the specific symptoms (sleep, pain, mood).^[8]

• Ordering serology for a typical erythema migrans lesion in a patient with plausible exposure — early Lyme disease is a clinical diagnosis, and serology is frequently falsely negative at this stage.
• Using a first-generation cephalosporin (e.g., cephalexin) for Lyme disease — it is not effective at any stage.
• Treating post-treatment Lyme disease syndrome, or a "chronic Lyme disease" diagnosis outside standard case definitions, with a prolonged or repeated antibiotic course — no proven benefit, and real risk of harm.^[8]
• Missing PR-interval prolongation or another sign of AV block on ECG in a patient with Lyme disease and cardiac symptoms — this needs hospital admission and possible temporary pacing, not outpatient management.
• Using serologic titres to "prove" cure or to guide re-treatment decisions — antibodies persist for years regardless of treatment success.
• Twisting or jerking a tick during removal, or using a folk remedy (petroleum jelly, heat, nail polish) instead of steady traction with fine-tipped tweezers.
• Assuming a patient cannot have Lyme disease because they do not recall a tick bite — most patients do not recall the bite.
• Using amoxicillin as single-dose postexposure prophylaxis — its short half-life makes a single dose ineffective, and it has not been studied for this use.
• Delaying indicated treatment while waiting for serology results in a patient with a clinical presentation compatible with neurologic or cardiac Lyme disease — treat based on clinical suspicion in these presentations rather than waiting for confirmation.

How to use this table: Doses are standard doses and require patient-specific confirmation, including renal/hepatic adjustment. Duration always depends on the specific clinical indication being treated — see Choose Initial Treatment for the stage-by-stage rule. Select any drug name to open its complete Pharmasist Drug Database page.

Tetracyclines

First-line agent for most indications; also the only agent used for single-dose postexposure prophylaxis.

Penicillins

Equal-efficacy oral alternative (amoxicillin) or IV alternative (penicillin G) to doxycycline/ceftriaxone.

Cephalosporins, second-generation

Equal-efficacy oral alternative to doxycycline and amoxicillin.

Cephalosporins, third-generation

Parenteral therapy for meningitis/other neurologic disease, hospitalized carditis, and refractory arthritis; step down to oral doxycycline once clinically improving.

Macrolides

2nd-line agent for early localized disease only — reduced efficacy compared with the tetracycline/penicillin/cephalosporin options above.

Not effective: first-generation cephalosporins (e.g., cephalexin) are not effective for Lyme disease at any stage.

Evidence note: Drug inventory, dosing, adverse effects, and comments reflect current IDSA/AAN/ACR guideline dosing, cross-checked against Public Health Agency of Canada guidance.^[1][2]