To the Editor:
Cerar et al
1
conclude that almost all Lyme disease patients treated for an erythema migrans rash with short-course antibiotic therapy have complete resolution of symptoms at 1 year following treatment. Unfortunately, the design of this Slovenian study promotes a false expectation of therapeutic success that cannot be generalized to all patients afflicted with Borrelia burgdorferi, the spirochetal agent of Lyme disease.According to the study protocol, all patients were started on antibiotic therapy within 1 week of developing an erythema migrans rash, and all received 2 weeks of antibiotics. Patient spouses or age-matched family members or friends served as controls, and follow-up was continued for 1 year. The authors state that 96%-97% of patients had complete resolution of Lyme disease symptoms at 1 year. However, as noted in Table 5 of that article,
1
8% of patients suffered from “osteoarthritis,” compared with only 1% of controls, a difference that was highly significant (P <.001). Thus, even under the best of treatment circumstances, the rate of arthritis in Lyme patients was 8 times the rate in the control population, and it is difficult to see how the authors could distinguish arthritis due to Lyme disease from an underlying condition unrelated to the tick-borne infection in this relatively young group of patients (median age, 53 years). While the predominance of women in the patient group (noted in Table 5) might partially explain the increased prevalence of arthritis,2
it does not account for the major difference in joint disease between the 2 groups. Moreover, the sex discrepancy between the patient and control groups strongly suggests that the choice of controls may have been inappropriate for the study.3
The lack of persistent symptoms reported by Cerar et al
1
contrasts markedly with a recent Norwegian study of neurologic Lyme disease.4
In that study, 48% of treated patients had persistent symptoms at 1 year of follow-up, and persistence of Lyme symptoms correlated with delayed diagnosis and female sex. Other studies have shown a similar excess of chronic symptoms compared with matched controls in patients treated for Lyme disease.5
, 6
, 7
Because an erythema migrans rash is recognized in only 35%-60% of Lyme disease patients,8
the prompt diagnosis and treatment of B. burgdorferi infection described by Cerar et al1
would probably not apply to the 40%-65% of Lyme disease patients without a rash. In these patients, persistent symptoms of Lyme disease would be expected to occur at a much higher rate than that reported in the Slovenian study, presumably due to persistent infection with the Lyme spirochete.8
It is important to recognize the limited generalizability of trials that depend on the presence of an erythema migrans rash and the prompt treatment of early Lyme disease, because missed diagnosis and delayed treatment are common factors in the evolution of chronic Lyme disease.9
, 10
References
- Subjective symptoms after treatment of early Lyme disease.Am J Med. 2010; 123: 79-86
- A meta-analysis of sex differences in prevalence, incidence and severity of osteoarthritis.Osteoarthritis Cartilage. 2005; 13: 769-781
- Gender bias in chronic Lyme disease.J Womens Health. 2009; 18: 1717-1718
- Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors.Eur J Neurol. 2010; 17: 118-123
- Chronic neurologic manifestations of Lyme disease.N Engl J Med. 1990; 323: 1438-1444
- The longterm clinical outcomes of Lyme disease.Ann Intern Med. 1994; 121: 560-567
- Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms.Int J Epidemiol. 2005; 34: 1340-1345
- Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with Lyme disease.Clin Infect Dis. 2007; 45: 149-157
- Consequences of treatment delay in Lyme disease.J Eval Clin Pract. 2007; 13: 470-472
- Generalizability in two clinical trials of Lyme disease.Epidemiol Perspect Innov. 2006; 3: 12-18
Article info
Footnotes
Funding: None.
Conflict of Interest: RBS serves without compensation on the medical advisory panel of QMedRx Inc. He has no financial ties to the company. LJ has no conflicts to declare.
Authorship: The work is original, and both authors had a role in writing the manuscript.
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Copyright
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
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- Subjective Symptoms after Treatment of Early Lyme DiseaseThe American Journal of MedicineVol. 123Issue 1
- The ReplyThe American Journal of MedicineVol. 123Issue 8
- PreviewWe appreciate the comments made by Cairns. Cairns asserts that post-Lyme syndrome is associated with a delay in antibiotic treatment, with neurologic symptoms in the acute phase, and with multiple erythema migrans skin lesions,1 but this conclusion is not evidence-based. The retrospectively controlled studies that she relied on in her meta-analysis certainly included such groups, but also were likely to have included patients with single erythema migrans skin lesions, and misdiagnosed patients.2 Our prospectively controlled study of patients with a single erythema migrans skin lesion may be considered as a starting point to address the question of whether post-Lyme disease syndrome exists in adults.
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- The ReplyThe American Journal of MedicineVol. 123Issue 8
- PreviewStricker and Johnson have incorrectly summarized our study protocol. Approximately 50% of our patients began antibiotic treatment after 1 week of illness, with 23.5% having symptoms in excess of 3 weeks before enrollment.1 Although we limited our study to patients with a single erythema migrans skin lesion, such patients are by far the most prevalent group of patients with Lyme disease in Slovenia. Of the 34,166 cases of Lyme disease reported in Slovenia from 2000 to 2008, more than 90% had erythema migrans.
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