Lyme disease (or borreliosis) is a tick-borne infection caused by certain species of the Borrelia genus (B. burgdorferi in the US, predominantly B. afzelii and B. garinii in Asia and Europe). There are three stages of Lyme disease. Stage I (early localized disease) is characterized by erythema migrans (EM), an expanding circular red rash at the site of the tick bite, and may be associated with flu‑like symptoms. In stage II (early disseminated disease), patients may present with neurological symptoms (e.g., facial palsy), migratory arthralgia, and cardiac manifestations (e.g., myocarditis). Stage III (late disease) is characterized by chronic arthritis and CNS involvement (late neuroborreliosis) with possible progressive encephalomyelitis. In Asia and Europe, further skin manifestations may also occur in stage II (lymphadenitis cutis benigna) and stage III (acrodermatitis chronica atrophicans). Lyme disease is a clinical diagnosis in patients presenting with EM. Serological tests (e.g., Western blot; enzyme-linked immunosorbent assay) can help support the clinical diagnosis, especially if the presence of EM is not known or questionable. Lyme disease is treated with antibiotics; the drugs of choice are doxycycline for localized disease and ceftriaxone for disseminated disease.
In the US: Borrelia burgdorferi, a microaerophilic spirochete bacteria
- Atypical and cystic forms of B. burgdorferi can persist in the body for years.
- In Europe and Asia: B. afzelii and B. garinii
- Rarely B. valaisiana, B. lusitaniae, B. spielmanii, and B. bavariensis infect humans.
- In the US: Borrelia burgdorferi, a microaerophilic spirochete bacteria
Various tick species: mainly Ixodes scapularis (deer or black-legged tick) in the northeastern and upper midwestern US
- Ixodes pacificus (western black-legged tick) in the northwestern US
- Ixodes ricinus (castor bean tick) in Europe
- Typically found in forests or fields on tall brush or grass
- The incidence of Lyme disease is highest between April and October (especially from June to August).
Increased risk of disease for:
- Outdoor workers (landscapers, farmers, etc.)
- Outdoor enthusiasts (i.e., hikers, hunters, etc.)
- Various tick species: mainly Ixodes scapularis (deer or black-legged tick) in the northeastern and upper midwestern US
- Deer, cattle
- Peromyscus leucopus, the white‑footed mouse, is the primary reservoir of B. burgdorferi in the US.
Stage I (early localized Lyme disease) 
Symptoms develop within 7–14 days after a tick bite
Erythema migrans (EM)
- Pathognomonic of early Lyme disease
- Occurs in approx. 70–80% of infected individuals 
- Usually a slowly expanding red ring around the bite site with central clearing (“bull's eye rash”)
- Typically warm, painless; possibly pruritic
- EM is often the only symptom.
- Self-limiting (typically subsides within 3–4 weeks)
- Flu‑like symptoms
Stage II (early disseminated Lyme disease) 
Symptoms develop 3–10 weeks after a tick bite
- Migratory arthralgia 
Cranial nerve disorders
- Most commonly peripheral facial nerve palsy
- Nocturnal radicular pain, paresthesia, and paresis
- Meningitis that may cause benign intracranial hypertension
- Polyneuropathy (mononeuritis multiplex, asymmetrical)
- Cranial nerve disorders
- Risk of cardiac arrhythmias (e.g., AV Block) and rarely myopericarditis
- Adams-Stokes syndrome
- Multiple erythema migrans lesions
- A rare, cutaneous manifestation of European Lyme disease (endemic for Ixodes ricinus)
- Characterized by a bluish-red nodular swelling typically located on the earlobe, face, or mamillae
- Often occurs near a previous or concurrent lesion of erythema migrans
- Localized lymphadenopathy is common.
- Resolves spontaneously
- Retinal vasculitis
Stage III (late Lyme disease) 
Symptoms develop months to years after the initial infection
Lyme arthritis 
- Inflammation of joint tissue colonized by Borrelia bacteria that may be intermittent or chronic and may cause permanent damage if left untreated
- Intermittent or persistent
- Monoarthritis or asymmetric oligoarthritis that typically affects the large joints (especially knee or elbow)
Late neuroborreliosis manifestations include:
- Aseptic (lymphocytic) meningitis
- Progressive encephalomyelitis
- Cognitive impairment
- Gait abnormality
- Bladder dysfunction
- Psychiatric abnormalities (e.g., depression, anxiety, bipolar disorder)
- Peripheral polyneuropathy
Acrodermatitis chronica atrophicans (Herxheimer disease)
- Chronic progressive dermatological disease due to infection with Borrelia afzelii that occurs only in Europe and Asia and most commonly affects women > 40 years of age
- Typically involving the extensor surface of the extremities
To remember important symptoms of Lyme disease, think of someone making a FACE (Facial nerve palsy, Arthritis, Carditis, Erythema migrans) when biting into a lime.
- After a tick bite, observe for erythema chronicum migrans.
- If stage I Lyme disease is likely (e.g., EM is present), start empiric antibiotics without further testing.
- If symptoms of Lyme disease arise in a patient with possible exposure (especially if recently traveled to an endemic area), conduct two-step serological testing.
- If signs of neuroborreliosis are present and other tests are inconclusive, consider additional procedures, such as a lumbar puncture for cerebrospinal fluid testing.
Two‑step serological testing
- Initial test: enzyme‑linked immunosorbent assay (ELISA)
- Confirmatory test: Western blot
- Detect IgG and IgM antibodies against Borrelia
- Results are only significant with corresponding clinical symptoms because:
- Positive results only demonstrate exposure to Borrelia (not necessarily current infection).
- False negative results are possible if seroconversion has not yet occurred (may take up to 8 weeks).
- Various diseases can lead to a false positive serology as a result of cross-reactions, including:
Possible blood test findings:
- Elevated ESR
- Elevated serum creatine phosphokinase, leukocytosis, leukopenia, anemia, and/or thrombocytopenia
- Elevated liver enzymes
Cerebrospinal fluid testing
- Signs of lymphocytic meningitis, including elevated protein (due to a disrupted blood-brain barrier) and pleocytosis
Measure intrathecal IgG or IgM antibodies
- Borrelia-specific intrathecal antibodies can be detected before serum antibodies.
- Consider testing for elevated chemokine CXCL 13 
If peripheral neurological symptoms are present: evaluate axonal damage
- Electromyography: reduced interference pattern
- Electronystagmogram: reduction in amplitude or complete absence of action potentials
Borrelia-specific intrathecal antibodies with normal protein and without pleocytosis indicate a past infection. Detection of elevated antibodies alone does not provide conclusive evidence of an active infection
- Commonly conducted if signs of arthritis are present, but results do not allow differentiation from septic arthritis without PCR
Synovial fluid findings
- Appearance: yellow and cloudy
- Leukocyte count: 3000–100,000/mm3 with > 50% neutrophils
- PCR test: positive
- Negative findings: Gram stain, culture, crystals
Rule of 7s: Children who meet all of the following criteria can be identified as at low risk for Lyme meningitis and may be treated accordingly in an outpatient setting until lab results become available.
- Headache for < 7 days
- < 70% of CSF mononuclear cells
- Absence of seventh or other cranial nerve palsy
- For erythema migrans: For details, see “Overview of annular skin lesions.”
For Lyme carditis
- See myocarditis.
- See arrhythmias.
- For Lyme arthritis
- See “Etiology” of major neurocognitive disorder.
- See “Differential diagnoses” of vitamin B12 deficiency.
- For differential diagnoses of tick bite: See “Overview of tick-borne diseases.”
The differential diagnoses listed here are not exhaustive.
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|Disseminated Lyme disease|| |
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Doxycycline is relatively contraindicated in pregnant/nursing women due to its adverse effects on growing bones and teeth. Administer amoxicillin (or cefuroxime axetil) instead.
If infection is likely (e.g., EM is present), start antibiotic treatment.
Possible complications following successful antibiotic treatment
Post-Lyme disease syndrome (PLDS)
- Description: a somewhat controversial syndrome (the medical community does not agree on its existence) following successful treatment of Lyme disease that is associated with pain, fatigue, and difficulty concentrating that lasts > 6 months 
- Differential diagnosis: somatoform disorders, unsuccessfully treated chronic Lyme disease
- Treatment: symptomatic treatment with general medical and psychosomatic support
- There is no approved vaccine on the market for Lyme disease. There was a Lyme disease vaccine in the past that offered temporary protection, but it was discontinued in 2002 because of low demand.
- Avoid prime habitats in areas known for Lyme disease.
Tick bite prevention: Prevent and properly manage tick bites to avoid exposure.
- Wear protective clothing: e.g., long-sleeved shirts, long pants, and light colors.
- Use tick repellent and pesticides.
- Check body for tick bites.
Remove ticks immediately
- Grasp the tick with tweezers directly above the skin's surface.
- Carefully pull upward with even pressure.
- Do not use nail polish remover, adhesives, oils, or similar substances to remove the tick. The tick should be removed quickly rather than waiting for it to detach slowly.
- Disinfect the site of the bite and dispose of the tick
- Observe the bite site for early detection of EM.
Post‑exposure prophylaxis for Lyme disease 
- Although controversial, post-exposure prophylaxis may be considered for patients who meet all of the following criteria:
- The attached tick can be identified as an adult or nymphal Ixodes scapularis tick.
- The tick has been attached for ≥ 36 hours (based on degree of engorgement or amount of time since exposure).
- Prophylaxis can be started within 72 hours of tick removal.
- The local rate of tick infection with B. burgdorferi is ≥ 20% (known to occur in parts of New England, parts of the mid‑Atlantic states, and parts of Minnesota and Wisconsin).
- The patient can take doxycycline (e.g., the person is neither pregnant nor breastfeeding, nor a child < 8 years of age).
- If the patient meets all the above criteria, 200 mg of doxycycline can be given to adults and 4.4 mg/kg to children of any age weighing < 45kg (maximum dose: 200 mg).