Lyme disease questions are classic Step 1 “bait-and-switch”: they look like simple infectious disease prompts, but the test writers really want you to recognize the vector, the stage-specific clinical findings, and the right diagnostic test at the right time. If you can anchor on Ixodes tick + erythema migrans + neuro/cardiac/arthritis timing, you’ll pick up a lot of easy points.
What is Borrelia burgdorferi?
Lyme disease is caused by Borrelia burgdorferi, a spirochete transmitted by the Ixodes (deer) tick.
Micro / classification (Step 1 essentials)
- Shape: Spirochete
- Gram stain: technically Gram-negative–like cell envelope, but poorly seen on Gram stain
- Best visualization: dark-field microscopy or silver stain
- Transmission: Ixodes tick
- Reservoir: classically white-footed mouse (and deer help maintain the tick life cycle)
First Aid cross-reference: Microbiology → Spirochetes → Borrelia (Lyme disease); tick-borne pathogens section.
Pathophysiology: why the symptoms “move around”
After a tick bite, B. burgdorferi:
- Replicates locally in the skin → erythema migrans
- Disseminates hematogenously → neuro + cardiac findings
- Persists in tissues (esp. synovium) → late arthritis
A high-yield way to remember it: skin → nerves/heart → joints.
High-yield immunology tie-in
- The rash and later manifestations are largely driven by host inflammatory response, not classic toxin-mediated disease.
- The organism has immune-evasion features (Step 1 framing): think antigenic variation and chronicity.
Clinical presentation by stage (the Step 1 money)
Stage 1: Early localized (days to weeks)
Hallmark: erythema migrans
- Expanding annular rash, often with central clearing (“bull’s-eye”)
- May be warm but typically not painful or pruritic
- Flu-like symptoms: fever, malaise, myalgias, headache
High-yield pearl: If the vignette is classic for erythema migrans, treat empirically—don’t wait for labs.
Stage 2: Early disseminated (weeks to months)
Neurologic
- Facial nerve palsy (CN VII) (uni- or bilateral)
- Lymphocytic meningitis
- Painful radiculoneuritis (shooting pains)
Cardiac
- AV conduction block (classically fluctuating degrees of AV block)
- Myopericarditis (less emphasized but possible)
Step-style clue: young person + hiking in Northeast/Upper Midwest + palpitations/syncope + new AV block.
Stage 3: Late disseminated (months to years)
- Migratory arthritis, classically knee (large joints)
- Can become intermittent/persistent inflammatory arthritis
High-yield pearl: Late Lyme arthritis can resemble inflammatory arthritides—timing and exposure history are key.
Diagnosis: don’t order the right test at the wrong time
The core Step 1 algorithm
- Erythema migrans + compatible exposure → clinical diagnosis → treat
- If symptoms suggest disseminated or late disease → two-tier serology
Two-tier testing (classic USMLE phrasing)
- ELISA (sensitive screening)
- Western blot (specific confirmation)
| Scenario | Best next step | Why |
|---|---|---|
| Classic erythema migrans | Treat empirically | Serology can be negative early |
| Neuro/cardiac symptoms after exposure | Two-tier serology ± CSF studies if meningitis suspected | Antibodies more likely present |
| Late arthritis | Two-tier serology | Serology usually positive |
High-yield caution: Early localized disease may be seronegative because antibodies haven’t risen yet—this is a common test trap.
Treatment (and what Step 1 expects you to choose)
Uncomplicated early disease
- Doxycycline is first-line in many Step questions
- Also covers potential coinfection (e.g., Anaplasma)—a common test-writer angle
If doxycycline is contraindicated
- Amoxicillin or cefuroxime
- Think: pregnancy, young children (exam-dependent; real-world nuance exists, but Step tends to avoid nuance and expects “avoid doxy”)
Severe disease (esp. neuro/cardiac)
- IV ceftriaxone
- Neuroborreliosis (e.g., meningitis) and significant carditis/advanced AV block are classic indications
| Clinical picture | Typical Step answer |
|---|---|
| Erythema migrans | Doxycycline (or amoxicillin/cefuroxime) |
| Facial nerve palsy with Lyme suspicion | Doxycycline (often) |
| Meningitis / significant neurologic disease | IV ceftriaxone |
| Symptomatic high-grade AV block | IV ceftriaxone (and supportive pacing if needed) |
| Late Lyme arthritis | Oral therapy often works; persistent cases may need further evaluation |
Jarisch–Herxheimer reaction? More classically tested with syphilis treatment, but Step may mention transient fever/chills after starting therapy for spirochetes.
High-yield associations & classic vignette triggers
Geography + exposure
- Northeast (New England, Mid-Atlantic), Upper Midwest (Wisconsin/Minnesota) in US vignettes
- Wooded areas, hiking/camping, pets bringing ticks indoors
Coinfection clue (Ixodes carries multiple pathogens)
If you see Lyme + unusual severity or lab abnormalities:
- Babesia: hemolytic anemia, jaundice; “Maltese cross” on smear
- Anaplasma: leukopenia, thrombocytopenia; intracellular inclusions in granulocytes
Step move: same tick, different bug—don’t anchor too hard.
Differentiating Borrelia from other spirochetes (quick board-style table)
| Organism | Key disease | Transmission | Signature findings | Diagnosis |
|---|---|---|---|---|
| Borrelia burgdorferi | Lyme disease | Ixodes tick | Erythema migrans, CN VII palsy, AV block, migratory arthritis | ELISA → Western blot (or clinical for EM) |
| Treponema pallidum | Syphilis | Sexual / vertical | Painless chancre; later rash incl palms/soles | VDRL/RPR then FTA-ABS |
| Leptospira interrogans | Leptospirosis | Animal urine, freshwater | Fever, myalgias, conjunctival suffusion; Weil disease | Serology/PCR |
| Borrelia recurrentis | Relapsing fever | Louse/tick | Recurrent febrile episodes | Blood smear (during fever) |
First Aid cross-reference: Spirochetes section—Lyme vs syphilis comparisons show up frequently.
First Aid-style “one-liners” to memorize
- Ixodes tick → Borrelia burgdorferi → erythema migrans → treat with doxycycline.
- Weeks to months: facial palsy, meningitis, AV block.
- Months to years: migratory arthritis (knee).
- Diagnosis: ELISA then Western blot (but clinical for erythema migrans).
- Severe neuro/cardiac: IV ceftriaxone.
Common Step 1 pitfalls (avoid these)
- Ordering serology for a classic erythema migrans rash and delaying treatment.
- Missing that AV block in a healthy hiker can be Lyme carditis.
- Confusing Lyme arthritis with septic arthritis: Lyme tends to be migratory/episodic and tied to exposure/timing.
- Forgetting doxycycline’s “bonus coverage” of tick-borne coinfections in test logic.