None of Nocton and colleagues' patients were seronegative. Nonetheless, their study and that by Mouristsen and colleagues were both cited by Dr. McCaulley as reporting positive PCR results in a subset of patients with Lyme disease who were seronegative. The PCR assay is extremely sensitive but must be formally tested in well-characterized patients with appropriate controls. The centers with the most Lyme disease experience have not found that patients with late-stage Lyme disease are frequently seronegative or that vague symptoms are cured by additional antibiotics. On the other hand, patients with true Lyme disease, if given the appropriate antibiotics for the appropriate duration, respond well.
Linden raise concerns about the validity and generalizability of the guidelines.
We are aware that several European studies evaluated the probability of Lyme disease in various patient groups. We believe that the biology of Lyme disease is sufficiently different that such studies may not apply to North America. Positive results on Lyme serology occur frequently in Europe without any clinical manifestations, but this is less common in the United States. We recommend that patients without clinical manifestations be neither tested nor treated for Lyme disease. Finally, we recognize that estimation of the prior probability of Lyme disease is difficult.