- Clinical science
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), a genus of facultative intracellular bacteria. 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), skin manifestations forming livid nodules along with lymphadenopathy (lymphadenitis cutis benigna; only in Europe and Asia), migratory arthralgia, and cardiac manifestations (e.g., myocarditis). Stage III (late disease) is characterized by chronic‑progressive skin atrophy (acrodermatitis chronica atrophicans; only in Europe), chronic arthritis and CNS involvement (late neuroborreliosis) with possible progressive encephalomyelitis. 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 is doxycycline for stage I and ceftriaxone for disseminated disease.
- Incidence: most commonly reported vector-borne disease in the US
- Geographical distribution: primarily the Northeast and upper Midwest
Epidemiological data refers to the US, unless otherwise specified.
In the US: Borrelia burgdorferi, an anaerobic, facultative intracellular 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, an anaerobic, facultative intracellular 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 northeastern US
- Ixodes ricinus (castor bean tick) in Europe
- Ticks populate many different areas, but require humid environments in order to survive.
- 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).
- Peromyscus leucopus, the white‑footed mouse, is the primary reservoir of B. burgdorferi in the US.
- Various tick species: mainly Ixodes scapularis (deer or black-legged tick); in the northeastern and upper midwestern US
Increased risk of disease for:
- Outdoor workers (landscapers, farmers, etc.)
- Outdoor enthusiasts (i.e., hikers, hunters, etc.)
Stage I (early localized Lyme disease)
- Symptoms develop within 7–14 days after a tick bite.
Erythema chronicum migrans (EM)
- Occurs in 80% of infected individuals
- Usually a circular, slowly expanding red ring around the bite site with central clearing
- Typically warm, painless
- 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 that can progress to Lyme arthritis
- Spreads from one joint to another
- Generally in large joints (especially knee or elbow)
- Early neuroborreliosis
- Risk of cardiac arrhythmias (e.g., AV Block) and rarely myopericarditis
- Multiple erythema migrans lesions
Borrelial lymphocytoma (or cutaneous lymphoid hyperplasia, lymphadenosis benigna cutis)
- Violaceous nodule
- Localized lymphadenopathy is common.
- Resolves spontaneously
- Uncommon manifestations have only been reported from Europe.
- Most commonly affected sites: ear lobe, face, mamillae; often appears close to the site of EM lesion
- Ocular manifestations: including conjunctivitis, retinal vasculitis, optic neuropathy, and uveitis
Stage III (late Lyme disease)
- Symptoms develop months to years after the initial infection
Chronic (10% of cases)
- Lasts over a year and may be intermittent or persistent
- Typically in large joints (especially knee or elbow)
- Late neuroborreliosis manifestations include:
- In Europe and Asia: acrodermatitis chronica atrophicans (ACA, also called Herxheimer's disease)
- Chronically progressive dermatological disease due to infection with Borrelia afzelii that occurs only in Europe and Asia and most commonly affects among women > 40 years of age
- Manifestation on the extensor side of extremities
- Stages in the course of the disease:
- After a tick bite, observe for erythema chronicum migrans. Suspicious rashes may be monitored over several days.
- If the patient history and clinical presentation indicate Stage I Lyme disease, empiric antibiotics may be started without further testing.
- If symptoms of Lyme disease arise in a patient with possible exposure (especially if a history of recent travel to an area with high vector density) → 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:
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
- Possible detection of chemokine CXCL 13 → studies not yet conclusive
- If peripheral neurological symptoms are present (to assess 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!
- Rule of 7s – Children who meet all of the following criteria can be identified as at low risk for Lyme meningitis and may accordingly be treated in an outpatient setting until lab results become available:
- Commonly conducted if signs of arthritis are present, but results do not allow differentiation from septic arthritis without PCR
- Synovial fluid findings
- For erythema migrans
- For Lyme carditis
- For Lyme arthritis
- For neuroborreliosis
The differential diagnoses listed here are not exhaustive.
|Tick-borne diseases (endemic to US) ||Pathophysiology / Epidemiology|| |
|Lyme disease|| || || |
|Tick paralysis|| || |
|Rocky Mountain spotted fever (RMSF)|| || || |
|Babesiosis|| || |
|Ehrlichiosis|| || |
(Human granulocytic ehrlichiosis)
| || |
|Tularemia  || || || |
|Colorado tick fever (CTF) || || |
|Tick-borne relapsing fever || || || |
|Southern tick‑associated rash illness (STARI)|| || || |
|Stages||Presentation||Adult therapy||Pediatric therapy and pregnant/lactating patients|
|Localized Lyme disease|| |
|Disseminated Lyme disease|
Doxycycline is relatively contraindicated in both children < 8 years old and pregnant/lactating 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!
Complications following successful antibiotic treatment
Post‑treatment Lyme disease syndrome (post‑Lyme disease syndrome, PLDS)
- Description: a controversial syndrome (the medical community does not agree on its existence) following successful treatment of Lyme disease that is associated with loss of performance, fatigue, and difficulty concentrating that may last up to 6 months
- Differential diagnosis: somatoform disorders
- Treatment: symptomatic treatment with general medical and psychosomatic support
- Post‑treatment Lyme disease syndrome (post‑Lyme disease syndrome, PLDS)
- There is no approved vaccine on the market.
- Avoid areas known for Lyme disease.
- 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 (PEP)
- Although controversial, PEP 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 mg/kg to children ≥ 8 years (maximum dose: 200 mg).