Late Manifestations of Lyme Disease and Their Treatment
The late manifestations of Lyme disease primarily include Lyme arthritis, chronic axonal polyneuropathy, and encephalopathy, which should be treated with specific antibiotic regimens based on the clinical presentation. 1, 2
Late Manifestations of Lyme Disease
Rheumatologic Manifestations
- Lyme arthritis is characterized by intermittent swelling and pain of one or several large joints, typically the knee, which can persist for weeks to months if untreated 1, 2
- Large knee effusions that are out of proportion to pain are typical, and Baker's cysts may develop 1
- Approximately 10% of patients may develop persistent joint swelling even after appropriate antibiotic treatment 2
- Synovial fluid typically shows mild-to-moderate inflammation with a median leukocyte count of 24,250 leukocytes/mm³, predominantly granulocytes 1
- Diagnosis requires serologic confirmation with positive two-tier testing (ELISA and IgG immunoblot) 1
Neurologic Manifestations
- Late neurologic Lyme disease may present as encephalomyelitis, peripheral neuropathy, or encephalopathy 1, 2
- Encephalomyelitis is a rare, unifocal or multifocal inflammatory CNS disease, primarily diagnosed in Europe 1
- Chronic axonal polyneuropathy typically presents as a mild, diffuse "stocking glove" neuropathy with intermittent limb paresthesias and reduced vibratory sensation in distal lower extremities 1
- Encephalopathy manifests as cognitive disorders, sleep disturbance, fatigue, and personality changes 1, 2
- Diagnosis requires two-tier seropositivity and evidence of intrathecal antibody production to B. burgdorferi 1
Treatment Approaches
Treatment of Lyme Arthritis
- First-line treatment: Oral antibiotics for 28 days 2
- For patients who fail to respond to oral therapy, a second course of oral antibiotics or a 2-4 week course of intravenous ceftriaxone (2 g daily) may be considered 1
- Approximately 10% of patients may have persistent joint swelling despite appropriate antibiotic therapy, which may last for months but eventually resolves 1
Treatment of Late Neurologic Manifestations
- Recommended treatment: Intravenous ceftriaxone 2 g daily for 2-4 weeks 1, 2
- Alternative parenteral regimens include:
- In the United States, treatment of Lyme disease-associated peripheral neuropathy with intravenous ceftriaxone usually results in improvement 1
- For encephalopathy, a 2-4 week course of intravenous ceftriaxone is recommended 1, 2
Important Clinical Considerations
Diagnostic Challenges
- Confirmation of late Lyme disease requires serologic testing with two-tier methodology (ELISA followed by IgG immunoblot) 1
- PCR testing of synovial fluid can provide additional diagnostic certainty in seropositive patients 1
- Positive PCR results in seronegative patients should be regarded with skepticism 1
Post-Treatment Considerations
- Antibodies against B. burgdorferi typically persist for months to years after successfully treated infection and should not be used as a marker of active disease 6
- Subjective symptoms may persist for weeks to months after treatment due to slow resolution of the inflammatory process, not persistent infection 1, 6
- Approximately 35% of patients have subjective symptoms at day 20,24% at 3 months, and 17% at 12 months after treatment 1, 6
Common Pitfalls to Avoid
- Misinterpreting persistent antibodies as evidence of treatment failure or ongoing infection 6
- Treating persistent subjective symptoms with prolonged or repeated courses of antibiotics when they may represent post-Lyme disease syndrome rather than active infection 1, 4
- Delaying diagnosis and treatment, which can lead to more severe complications 7
- Failing to recognize subtle neurologic symptoms in patients with Lyme arthritis, which may require intravenous rather than oral antibiotics 1
By following these evidence-based treatment approaches for late manifestations of Lyme disease, clinicians can effectively manage these conditions while minimizing adverse effects from antibiotic therapy and improving patient outcomes.