Treatment of Lyme Arthritis
For patients with Lyme arthritis, initiate oral antibiotic therapy for 28 days as first-line treatment, with doxycycline 100 mg twice daily (adults) or amoxicillin 500 mg three times daily (children <8 years, pregnant women) as the preferred regimens. 1
Initial Treatment Approach
First-Line Oral Therapy (28 Days)
- Doxycycline 100 mg twice daily is the preferred agent for adults and children ≥8 years old 1, 2
- Amoxicillin 500 mg three times daily is the alternative for children <8 years, pregnant women, or those intolerant to doxycycline 1, 2
- Cefuroxime axetil 500 mg twice daily is another effective oral option 1, 3
The 2020 IDSA/AAN/ACR guidelines provide a strong recommendation with moderate-quality evidence for 28-day oral therapy, representing an update from the 2006 guidelines that also supported this approach. 1 Oral therapy is easier to administer, has fewer serious complications, and is considerably less expensive than intravenous antibiotics. 1
Management of Inadequate Response
Partial Response (Mild Residual Joint Swelling)
After completing the initial 28-day course, if mild residual swelling persists but has substantively improved: 1
- Consider observation for several months before re-treatment, as inflammation resolves slowly even after successful bacterial eradication 1
- Second course of oral antibiotics for up to 28 days may be reasonable for patients with modest synovial proliferation who prefer avoiding IV therapy 1
- Exclude other causes of joint swelling and assess medication adherence before proceeding 1
No or Minimal Response (Moderate to Severe Joint Swelling)
For patients with no improvement or worsening after initial oral therapy: 1
- Administer IV ceftriaxone 2 g once daily for 2-4 weeks 1
- This represents a weak recommendation with low-quality evidence, but is the preferred approach over repeating oral antibiotics 1
Post-Antibiotic (Antibiotic-Refractory) Lyme Arthritis
After completing both one course of oral antibiotics AND one course of IV antibiotics (total ≥8 weeks) without resolution, refer to a rheumatologist rather than continuing antibiotics. 1
Treatment options at this stage include: 1
- Disease-modifying antirheumatic drugs (DMARDs) such as hydroxychloroquine
- Biologic agents
- Intra-articular corticosteroid injections (only after PCR negativity confirmed)
- Arthroscopic synovectomy if significant pain or functional limitation persists
Antibiotic therapy beyond 8 weeks provides no additional benefit once IV therapy has been included. 1
Critical Pitfalls to Avoid
During Active Treatment
- Avoid intra-articular corticosteroids during the initial treatment phase before bacterial eradication is confirmed 1
- Do not use first-generation cephalosporins, fluoroquinolones, carbapenems, vancomycin, metronidazole, or tinidazole—these are ineffective against B. burgdorferi 2, 4
- Macrolides (azithromycin, clarithromycin) are less effective than first-line agents and should only be used when patients cannot tolerate doxycycline, amoxicillin, or cefuroxime 2, 4
Monitoring and Re-treatment Decisions
- Do not use serologic testing to monitor treatment response—antibodies remain positive for months to years after successful treatment 2, 4
- Clinical improvement is the most reliable indicator of treatment success 2, 4
- Wait several months before considering re-treatment, as inflammation resolves slowly even after bacterial eradication 1
Persistent Symptoms Without Objective Findings
- Do not prescribe additional antibiotics for persistent nonspecific symptoms (fatigue, pain, cognitive impairment) without objective evidence of active disease 1
- Subjective symptoms may persist in 35% at day 20,24% at 3 months, and 17% at 12 months post-treatment without indicating treatment failure 2
Special Considerations
Neurologic Complications
A small number of patients treated with oral agents may subsequently develop overt neuroborreliosis, which requires switching to IV ceftriaxone 2 g once daily for 2-4 weeks. 1, 5 This highlights the importance of monitoring for new neurologic symptoms during and after treatment.
Risk Factors for Antibiotic-Refractory Disease
Children ≥10 years old, those with prolonged arthritis at diagnosis, knee-only arthritis, or worsening after starting antibiotics are at higher risk for antibiotic-refractory disease. 6 These patients may benefit from earlier rheumatology referral after failing initial therapy.
Treatment-Associated Adverse Events
Serious adverse events can occur with IV ceftriaxone, including drug-induced autoimmune hemolytic anemia and renal failure, reinforcing the importance of using oral therapy first-line when appropriate. 7 Treatment-associated adverse events occur in 37% of children with antibiotic-refractory disease versus 15% of responders. 6