Approach

Antibiotic therapy is the mainstay of treatment.

Post-exposure prophylaxis

Post-exposure prophylaxis with a single dose of doxycycline is recommended for significant exposures under the following circumstances:[25]

  • High-risk tick bite: an Ixodes tick bite; at least an estimated 36 hours of attachment; and in an area highly endemic for Lyme disease.

  • Prophylaxis is started within 72 hours of tick removal.

  • Doxycycline is not contraindicated. Doxycycline is not recommended during pregnancy and lactation. In some countries outside of the US, doxycycline is not recommended in younger children (see below).

An area with Borrelia burgdorferi prevalence of >20% in local ticks is considered a highly endemic area.[25]

Patients who cannot take doxycycline for post-exposure prophylaxis are started on treatment if early symptoms develop.

Erythema migrans

Treatment of Lyme disease associated with erythema migrans in the absence of cardiovascular and neurological manifestations is as follows:[25][38][39][40][41][42][43][44][45]

  • Doxycycline for 10 days; or amoxicillin or cefuroxime for 14 days. In the UK, longer courses of doxycycline and amoxicillin are recommended (21 days).[33]​​

  • A randomised, open-label trial of 300 adults in Slovenia with solitary erythema migrans found that oral doxycycline for 7 days was non-inferior to 14 days, raising the possibility of a shorter treatment course. Larger studies from different locales are required to validate this finding.[46]

  • Doxycycline is not recommended in pregnant or lactating women; amoxicillin for 14 days is the recommended treatment.

  • Doxycycline, amoxicillin, or cefuroxime may be used in children.[25][47] In some countries outside of the US, doxycycline is not recommended in younger children (see below).

  • Macrolides are not recommended for first-line treatment, but reserved for patients who are intolerant to all first-line antibiotics. Azithromycin can be used for 7-10 days in these cases. In the US, macrolides are generally felt to be less effective than amoxicillin, based upon findings from a randomised trial which demonstrated improved resolution of symptoms and reduced risk of relapse in patients treated with amoxicillin compared with those treated with azithromycin.[48] In the UK, longer courses of azithromycin are recommended (17 days).[33]​​

  • When erythema migrans cannot be distinguished from community-acquired cellulitis, cefuroxime or amoxicillin/clavulanate, effective for both conditions, is recommended.

Cardiac involvement

Hospitalisation, intravenous antibiotics, and continuous ECG monitoring are recommended for patients with, or at risk for, severe cardiac complications, including those with chest pain, syncope, dyspnoea, atrioventricular block, PR interval 300 milliseconds or longer, other arrhythmias, or clinical manifestations of myopericarditis.[25] Ceftriaxone is the drug of choice for both adults and children. Alternative agents include cefotaxime or benzylpenicillin. Doxycycline is an alternative agent for patients with cardiac complications who are intolerant of penicillins or cephalosporins, but it is not recommended during pregnancy and lactation. In some countries outside of the US, doxycycline is not recommended in younger children (see below). Patients may be switched to oral antibiotics when there is evidence of clinical improvement.

Temporary pacing is recommended for patients with symptomatic bradycardia who cannot be managed medically.[25]​​ Patients with Lyme carditis who do not need to be hospitalised are treated with oral antibiotics.[25] Oral antibiotic options are doxycycline, amoxicillin, or cefuroxime.

Recommended duration of antibiotic therapy for Lyme carditis is 14-21 days.

Lyme arthritis

Treatment depends on the type and extent of infection:[25]

  • Patients with Lyme arthritis are treated with oral antibiotics including doxycycline, amoxicillin, or cefuroxime for 28 days; non-steroidal anti-inflammatory drugs (NSAIDs) may be used adjunctively for symptom relief.

  • Patients with recurrent or persistent joint swelling after an initial course of oral antibiotics should receive 2-4 weeks of parenteral therapy with intravenous ceftriaxone, rather than a second course of oral antibiotics.

Patients with arthritis who are non-responsive to antibiotic treatment should be referred to a rheumatologist for further work-up and appropriate treatment of other causes.[25]

Neurological Lyme disease (neuroborreliosis)

Patients with acute neurological manifestations of Lyme disease should be treated with one of the following four antibiotics: intravenous ceftriaxone, cefotaxime, benzylpenicillin, or oral doxycycline for 2-3 weeks.[25] Although parenteral antibiotics are generally preferred for patients with neurological complications, oral doxycycline has been shown to be equally effective in early disease.[34]

Patients with early neurological Lyme disease confined to the meninges, cranial nerves, nerve roots, or peripheral nerves (Bannwarth syndrome) can be treated with a 2-week course of either an oral antibiotic (doxycycline) or an intravenous antibiotic (ceftriaxone, cefotaxime, or benzylpenicillin).[34]

Although rare, patients involvement of the brain parenchyma, such as those with focal findings or MRI findings, should be treated with intravenous antibiotics for 2-4 weeks.[25] Based on small studies, patients with early neuroborreliosis with manifestations such as myelitis, encephalitis, and vasculitis require intravenous antibiotics for 2 weeks.[34]

For late Lyme disease with peripheral neuropathy and acrodermatitis chronica atrophicans, treatment with either oral doxycycline or intravenous ceftriaxone is recommended.[25][34] However, if patients have central nervous system (CNS) manifestations, such as myelitis, encephalitis, and vasculitis, they should be treated with intravenous ceftriaxone.

Patients with Lyme disease-associated facial palsy should be treated with antibiotics; US guidelines recommend oral doxycycline.[25] Corticosteroids may have been started, as they are used for the treatment of idiopathic facial nerve palsy; however, they may be discontinued if the cause is identified as borreliosis.[25]

Prolonged antibiotic treatment (14 weeks) in patients with persistent Lyme borreliosis-attributed symptoms has not been shown to have a beneficial effect on cognitive performance, compared with short-term treatment (2 weeks).[49]

Doxycycline in children

Previously, the use of doxycycline was limited to children ≥8 years, but comparative data suggest it is not likely to cause visible teeth staining or enamel hypoplasia in younger children.[50]​ One 2023 systematic review also concluded that early childhood doxycycline exposure is not associated with dental staining or enamel defects.[51]​ While doxycycline is now recommended in the US for children <8 years for certain indications (including Lyme disease), in other countries there may still be age restrictions in place and you should consult your local guidance

Lyme disease in pregnancy

The data for vertical transmission of Lyme disease in pregnancy are inconclusive, and evidence on adverse birth outcomes is inconsistent. One meta-analysis of nine studies showed that the prevalence of adverse birth outcomes was significantly lower in women who were treated for gestational Lyme disease, compared with those who were not treated during pregnancy (11% vs. 50%). Therefore, prompt diagnosis and treatment of Lyme disease during pregnancy is recommended.[52] Doxycycline is not recommended during pregnancy or lactation; amoxicillin is the recommended treatment.

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