Lyme Disease Recurrences May Be Reinfections, Not Relapses

Lara C. Pullen, PhD

November 14, 2012

Repeat episodes of Lyme disease (erythema migrans) in antibiotic-treated patients result from reinfection and not relapse, according to a new study. This conclusion was made from genotyping the isolates of Borrelia burgdorferi from paired consecutive episodes of erythema migrans.

Skin lesion typical of Lyme disease.

Robert B. Nadelman, MD, from New York Medical College in Valhalla, and colleagues published results of their genotyping study in the November 15 issue of the New England Journal of Medicine. The study focused on the ospC genotypes of B burgdorferi. Although 24 paired episodes were initially identified for the study, isolates of B burgdorferi for ospC genotyping were not available from 2 of the culture-positive paired episodes.

The study included 22 paired episodes and revealed 12 different ospC genotypes: 8 different ospC genotypes at the initial episode of erythema migrans and 11 different genotypes at the second episode. Notably, not a single patient with recurrent symptoms had the same strain of bacteria in the second episode as they did in the first.

The study was not powered to determine whether humans mount type-specific immunity to ospC genotypes.

In the first episode, 18 (82%) of 22 of patients had systemic symptoms. Evidence of disseminated infection was present in 13 (59%) of 22 patients. Many patients in the study who were successfully treated with antibiotics in the first episode went on to again be culture positive for B burgdorferi during the second episode.

The data are consistent with the clinical and epidemiological evidence, which suggests that the patients had reinfections.

Kyle Brizendine, MD, from the Cleveland Clinic in Ohio, reviewed the study and spoke with Medscape Medical News by telephone. He noted that "physicians should feel comfortable that the recommended first-line drugs are extremely effective."

In an accompanying editorial also published in the New England Journal of Medicine, Allen C. Steere, MD, from Harvard Medical School in Boston, Massachusetts, writes, "As concluded by the Infectious Disease Society of America, there is no evidence of persistent B burgdorferi infection in human patients after recommended courses of antibiotic therapy. Although B burgdorferi infection may persist for years in untreated patients, the weight of evidence is strongly against persistent infection as the explanation for persistent symptoms in antibiotic-treated patients with Lyme disease."

Although evidence points to eradication of the bacteria with appropriate antibiotic treatment, some patients report continued symptoms of pain and fatigue. Dr. Steere acknowledges this in the editorial and writes, "Although most patients with Lyme arthritis have a response to recommended antibiotic therapies, a small percentage of patients have persistent synovitis for months or several years after receiving oral and intravenous antibiotic therapy for 2 to 3 months; this condition is called antibiotic-refractory arthritis. Rather than persistent infection, infection-induced autoimmunity, retained spirochetal antigens, or both may play a role in this outcome."

This study was supported in part by grants from the National Institutes of Health and the William and Sylvia Silberstein Foundation to one of the authors. Dr. Nadelman has reported receiving consulting fees from Guidepoint Global and Decision Resources and serving as an expert witness in medical malpractice cases regarding Lyme disease. One coauthor has reported receiving consulting fees from Baxter, serving as an expert witness in medical malpractice cases regarding Lyme disease, holding stock in Abbott, and receiving grant support to his institution from Bio-Rad, DiaSorin, Immunetics, and bioMérieux. The other authors have disclosed no relevant financial relationships. Dr. Brizendine also has disclosed no relevant financial relationships. Dr. Steere has reported receiving consultant fees from Merck to review information on Lyme disease vaccination.

N Engl J Med. 2012;367:1883-1890.