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New Lyme Disease Guidelines for Erythema Migrans Lesions Miss the Mark

      To the Editor:
      If the primary treatment goal for managing patients with erythema migrans (EM) rashes is to restore patients to their pre-Lyme health status, then the guidelines endorsed by Auwaerter et al
      • Auwaerter PG
      • Kobayashi T
      • Wormser GP
      Guidelines for Lyme disease are updated.
      are both inadequately sourced and potentially dangerous.
      • Maloney EL
      Evidence-based, patient-centered treatment of erythema migrans in the United States.
      Of the 2 trials cited by the authors in support of a 10-day doxycycline regimen, only 1 is applicable to US patients. In that study, almost half of the subjects in each arm failed to complete the 30-month trial.
      • Wormser GP
      • Ramanathan R
      • Nowakowski J
      • et al.
      Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial.
      At the 12-month observation point, 72% (44 out of 61) had a complete response to therapy, suggesting that this regimen is not highly effective and puts many at risk for post-treatment sequalae that adversely impact quality of life.
      • Rebman AW
      • Bechtold KT
      • Yang T
      • et al.
      The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with posttreatment Lyme disease syndrome.
      The other study was conducted in Europe.
      • Stupica D
      • Lusa L
      • Ruzic-Sabljic E
      • et al.
      Treatment of erythema migrans with doxycycline for 10 days versus 15 days.
      Due to differences between the US and European Lyme-inducing Borrelia species,
      • Makhani N
      • Morris SK
      • Page AV
      • et al.
      A twist on Lyme: the challenge of diagnosing European Lyme neuroborreliosis.
      ,
      • Jungnick S
      • Margos G
      • Rieger M
      • et al.
      Borrelia burgdorferi sensu stricto and Borrelia afzelii: Population structure and differential pathogenicity.
      its findings are not generalizable to US patients and should not be used to guide treatment decisions in the United States.
      • Maloney EL
      Evidence-based, patient-centered treatment of erythema migrans in the United States.
      Missing from the guidelines and the authors’ discussion regarding the utility of 10 days of doxycycline is the prospective study by Massarotti et al,
      • Massarotti EM
      • Luger SW
      • Rahn DW
      • et al.
      Treatment of early Lyme disease.
      where the clinical failure rate was 36% (8 out of 22). With regard to amoxicillin and cefuroxime, there is no US trial data to support the recommended 14-day duration; clinicians should be told that the US trials investigating these agents as monotherapy used 20-day regimens.
      • Maloney EL
      Evidence-based, patient-centered treatment of erythema migrans in the United States.
      Additionally, several US EM investigators observed that patients with multiple EM lesions were at higher risk of long-term treatment failure,
      • Maloney EL
      Evidence-based, patient-centered treatment of erythema migrans in the United States.
      yet the guidelines the authors promote fail to acknowledge or act on those insights.
      It is challenging to provide evidence-based medical care when there is little or no high-quality evidence to rely on. It is harder still when influential authors promote inadequate guidelines without meaningfully disclosing their shortcomings. Clinicians and their patients deserve better.

      References

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        • Kobayashi T
        • Wormser GP
        Guidelines for Lyme disease are updated.
        Am J Med. 2021; 134: 1314-1316
        • Maloney EL
        Evidence-based, patient-centered treatment of erythema migrans in the United States.
        Antibiotics (Basel). 2021; 10: 754https://doi.org/10.3390/antibiotics10070754
        • Wormser GP
        • Ramanathan R
        • Nowakowski J
        • et al.
        Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial.
        Ann Intern Med. 2003; 138: 697-704
        • Rebman AW
        • Bechtold KT
        • Yang T
        • et al.
        The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with posttreatment Lyme disease syndrome.
        Front Med (Lausanne). 2017; 4: 224https://doi.org/10.3389/fmed.2017.00224
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        • Lusa L
        • Ruzic-Sabljic E
        • et al.
        Treatment of erythema migrans with doxycycline for 10 days versus 15 days.
        Clin Infect Dis. 2012; 55: 343-350
        • Makhani N
        • Morris SK
        • Page AV
        • et al.
        A twist on Lyme: the challenge of diagnosing European Lyme neuroborreliosis.
        J Clin Microbiol. 2011; 49: 455-457
        • Jungnick S
        • Margos G
        • Rieger M
        • et al.
        Borrelia burgdorferi sensu stricto and Borrelia afzelii: Population structure and differential pathogenicity.
        Int J Med Microbiol. 2015; 305: 673-681
        • Massarotti EM
        • Luger SW
        • Rahn DW
        • et al.
        Treatment of early Lyme disease.
        Am J Med. 1992; 92: 396-403