Feder- Response to Critics of Chronic Lyme Article
In response to critics discussing Feder's A Critical Appraisal of "Chronic Lyme Disease" article, located here:
http://www.nejm.org/doi/full/10.1056/NEJMra072023
My colleagues and I agree with Mayer and Merz that Ixodes scapularis ticks can transmit Anaplasma phagocytophilum, Babesia microti, or rarely, both of these pathogens, and that in the right clinical setting, appropriate diagnostic testing for these agents is warranted.1 There is no evidence that these or any other ticks transmit bartonella.1 There is also no evidence for the existence of chronic anaplasma infection in humans, nor is there any published clinical evidence that an active tick-borne coinfection is the explanation for symptoms in the vast majority of patients with post–Lyme disease syndrome.2
Maloney raises several issues that we fully address in our article. B. burgdorferi, like other spirochetes, predominantly resides in the extracellular matrix. Moreover, patients with post–Lyme disease syndrome who received a 2-month course of doxycycline, an antibiotic that enters cells, had no greater improvement than those who received placebo.2
Holmes attaches undue significance to serologic reactivity that fails to meet conventional guidelines for seropositivity. It is important to recognize that reactivity to one or more antigens of B. burgdorferi on immunoblot occurs in more than 50% of the general population because of the production of cross-reactive antibodies directed at either other bacteria or nonbacterial antigens. Indeed, the principal reason that the U.S. Public Health Service recommended both two-tier testing and the use of evidence-based criteria for interpreting immunoblots in 1995 was to reduce the number of false positive results. Use of immunoblot criteria with poor specificity contributes to substantial numbers of misdiagnosed cases and furthers public misperceptions of Lyme disease.
We disagree with Volkman. Seronegativity is unexpected in patients with any manifestation of late Lyme disease (e.g., Lyme arthritis).1 Cell-proliferation assays do not provide adequate evidence for the existence of seronegative Lyme disease because this method has an unacceptably high rate of false positive results (in one study the specificity was only 33%3). Similarly, certain studies using PCR assays in patients with possible Lyme disease also failed to meet high-level standards for scientific evidence. False positive results for the detection of DNA of B. burgdorferiby PCR testing are well recognized.4 Approaches to improving the reliability of PCR tests include avoiding nested-primer protocols, sequencing amplicons to confirm their identity, and using positive controls with distinctive sequences. Positive results may be confirmed by amplification of multiple gene targets and testing in separate laboratories in different locations.
The term “clinical equipoise,” used by Cameron, is difficult to justify in view of the published reports of five double-blind, randomized, placebo-controlled clinical trials that have convincingly demonstrated that antibiotic treatment of post–Lyme disease symptoms is not in the best interests of patients.5 Our article summarizes the consensus among clinicians who practice evidence-based medicine, such as Drapkin, whom we thank for his comments.
Henry M. Feder, Jr., M.D.
University of Connecticut Health Center, Farmington, CT 06030
for the Ad Hoc International Lyme Disease Group
http://www.nejm.org/doi/full/10.1056/NEJMra072023#t=letters