Cognition problems fuel Lyme disease debate

Clinical Psychiatry News, Oct, 2002 by Nancy Walsh

NEW YORK -- Experts on Lyme disease from North America and Europe presented the latest findings on pathogenesis, epidemiology, diagnosis, and treatment at an international conference on tick-borne diseases, sponsored by Imedex.

Meanwhile, across the street from the conference, protesters from patient advocacy groups clamored for attention, accusing the physicians of ignoring their cries for help in managing devastating long-term complications of the disease.

Most patients infected by the spirochete Borrelia burgdorferi experience an acute illness characterized by the distinctive rash erythema migrans. They also may have neurologic, arthritic, and cardiac involvement but typically respond to one or two courses of treatment with either doxycydine or amoxidillin.

But a subset of patients develops symptoms months to years later, including altered cognition and mood, pain, and profound fatigue. The reasons remain unknown. Patients and some clinicians believe that these symptoms result from persistent spirochetal infection, whereas most researchers believe that the postinfection maladies experienced by these patients have other explanations such as re-infection, immune dysregulation, or an autoimmune inflammatory response. One recent article described the "psycho-pathogenesis of chronic Lyme disease," likening it to syndromes such as chronic fatigue and multiple chemical sensitivity (Environ. Health Perspect. 110[suppl. 4]:607-11, 2002).

"Few if any, other topics in clinical research have generated more controversy," Dr. Mark S. Klempner said at the conference. "The discourse between patients, patient advocacy groups, researchers who study these patients, and clinicians has become progressively more uneasy to the detriment of all," he said at the beginning or his presentation on controlled clinical studies on patients with persistent symptoms after treatment for Lyme disease.

To date, only one controlled clinical trial has been published evaluating

the effects of long-term antibiotic therapy on chronic manifestations of Lyme disease, Dr. Klempner said at the conference.

In that study, for which Dr. Klempner of Boston University was the principal investigator, 129 patients, 78 of whom were seropositive for IgG antibodies to B. burgdorferi and 51 of whom were seronegative, were randomized to receive intravenous ceftriaxone, 2 g daily for 30 days, followed by oral doxycycline, 200 mg daily for an additional 60 days, or matching placebos.

They were required to have a history of acute Lyme disease and to have completed at least one course of appropriate antibiotic therapy. Their chronic symptoms had to have persisted for at least 6 months. Baseline assessments determined that both mental and physical impairments were severe in the study patients.

The study design had originally called for the enrollment of 260 patients. But when the interim analysis was done, the trial was stopped because no significant differences were seen between the treatment group and the placebo group, and it was judged "highly unlikely" that significant differences would be found with full enrollment (N. Engl. J. Med. 345[2]:85-92, 2001).

Of the 51 patients in the antibiotic group who had been enrolled in the study for at least 180 days, 28 (55%) reported improved health status, as did 22 of the 53 patients in the placebo group (42%). Seven of the 51 patients (14%) in the antibiotic group reported worsened health status, as did 10 of 53 (19%) in the placebo group.

The study also sought to answer whether objective evidence existed of persistent infection. "Using the currently best available tests of culture and [polymerase chain reaction], we could find no patients with a positive culture or positive [polymerase chain reaction test] in blood or spinal fluid at any time during the study," he said.

Dissenters spoke during the question-and-answer sessions following the presentations, arguing that their abstracts had been rejected without cause by the program committee, and that their views about treating Lyme disease patients with longer-term antibiotics were being deliberately ignored.

"There are two schools of thought about the nature of Lyme disease, and the design of the conference made it appear that there is a monolithic consensus on what Lyme disease is," Dr. Kenneth Liegner, whose two abstracts were rejected, said in an interview.

Publication of guidelines for the treatment of Lyme disease by the Infectious Diseases Society of America has increased the difficulties faced by Dr. Liegner and other clinicians who treat chronic Lyme disease. Of patients who remain unwell after standard courses of antibiotics, the guidelines state: "To date, there are no convincing published data that repeated or prolonged courses of either oral or intravenous antimicrobial therapy are effective for such patients. The consensus of the [Infectious Diseases Society of America] expert panel members is that there is insufficient evidence to regard 'chronic Lyme disease' as a separate diagnostic entity" (Clin. Infect, Dis. 31[suppl. 1]:1-14, 2000).