Chronic Lyme Disease

What's up doc? Lyme disease is perplexing
By Dr. Jeff Hersh / Daily News Correspondent
Tuesday, June 7, 2005

Last week, I began discussing Lyme disease, including the symptoms from stage 1 or early Lyme disease, as well as those from stage 2 or early disseminated disease. Stage 3 or chronic Lyme disease is a trickier topic.

As I noted last week, any patient with symptoms and a history suggestive of Lyme disease should be treated with an appropriate course of antibiotics. This may be a course of oral antibiotics (usually for at least several weeks to a month) or a course of intravenous antibiotics (again, typically for at least several weeks to a month). The symptoms of stage 3 Lyme disease may manifest weeks, months or even years after the initial tick bite, and occur despite previous treatment with antibiotics.

Borrelia burgdorferi is a spirochete type of bacteria, the same type -- but NOT the same bacteria -- that is responsible for syphilis. Syphilis is a disease whose course is separated into stages, with the early stage having localized symptoms (classically a painless rash or sore), and if untreated a second stage with more systemic symptoms, and finally a third stage (which usually occurs years after the initial infection) where the cardiac heart or neurologic systems can be involved.

Typical symptoms of chronic Lyme disease include the triad of fatigue/malaise, joint or muscle pain/stiffness and neuorcognitive/psychiatric symptoms. Bouts of arthritis, with the knees being the most common joint involved, are common in patients with chronic Lyme disease, as is memory impairment and/or difficulty concentrating. The particular manifestations can be different from patient to patient, and many possible symptoms have been attributed to chronic Lyme disease.

As I noted in last week's column, the blood tests for Lyme disease are not ideal. Patients who are treated with antibiotics early in the course of their disease may not build levels of certain antibodies, and so may test negative for Lyme disease, even when the more specific Western blot test is done in addition to the screening ELISA test.

In addition, for unknown reasons, other patients may not build measurable levels of those antibodies that are tested for. What this means is that patients with a documented history of Lyme disease can develop chronic Lyme disease and still have negative blood tests. These patients are called sero-negative patients, as opposed to those who have positive antibody titers and are called sero-positive patients. The lack of a definitive test for Lyme disease is just one of the issues that makes this such a tricky disease, both to study and to treat.

It is not clear what causes the symptoms in patients with chronic Lyme disease. Stage 1 or early Lyme disease is felt to be due to the initial infection with the bacteria, and stage 2 disease thought to be due to dissemination of the bacteria as it becomes a more generalized systemic infection. The cause of the symptoms in stage 3 or chronic Lyme disease is not understood, although there are many theories:

- Ongoing infection with the bacteria

- Re-infection with the bacteria

- An autoimmune or inflammatory response to the infection, with the assumption that the infection itself has cleared

- Some other cause

Some studies have suggested that there is a genetic predisposition to developing chronic Lyme disease, and this may support the idea that it is due to a persistent autoimmune or inflammatory response to a previous but inactive infection.

It seems logical that if chronic Lyme disease is due to an ongoing or re-infection that further antibiotic therapy is indicated. In 1996 the New England Medical Center right here in Massachusetts was awarded a grant by the National Institute of Allergy and Infectious Diseases to study this issue. Both sero-positive and sero-negative patients with documented histories of Lyme disease and symptoms consistent with chronic Lyme disease were recruited for the study, and were treated either with placebo or with intravenous antibiotics for 30 days followed by 60 days of antibiotics by mouth, for a total 90-day treatment course. This study found that about 40 percent of both the placebo and treatment groups improved, but there was no difference between the groups, and hence the study was stopped early.

In another study, this one run by a researcher at Columbia University in New York, patients with chronic Lyme disease who had memory impairment as one of their symptoms were studied. The treatment group of these patients received a 10-week course of intravenous antibiotics, and there was a statistically significant benefit demonstrated for treated patients.

There have been other studies done as well, although to my knowledge no conclusive study of whether antibiotic treatment is useful, and if so how long and what antibiotics should be used.

This seems to leave us with more questions than answers. Some researchers advocate even longer courses of antibiotic therapy, noting that other diseases -- such as tuberculosis -- require very extensive treatment times to eradicate infection. Others note the cause of symptoms is unlikely to be chronic infection, and advocate treatments aimed at supportive care and symptomatic treatment.

Chronic Lyme disease is still not very well understood. This makes it impossible to give any evidence-based advice to those people who suffer from it. I think the bottom line is that chronic Lyme disease is an entity that needs a lot more scientific study. The hope is that future research will shed light on this disease, and that successful treatments will be discovered.


( Jeff Hersh, Ph.D., M.D., F.A.A.P., F.A.C.P., F.A.A.E.P., can be reached at DrHersh@juno.com. )