Lyme Disease

Chronic Lyme Disease

What is “chronic Lyme disease”?

Lyme disease is an infection caused by the bacterium Borrelia burgdorferi. It is easily treatable with oral antibiotics.

Chronic Lyme disease (CLD) is a controversial term sometimes used to describe a poorly defined group of illnesses characterized by a broad range of symptoms that often include, but are not limited to, chronic fatigue, pain, and neurocognitive disorders. The term has been used to describe any number of illnesses both in individuals with a documented history of successfully treated Lyme disease (post-treatment chronic Lyme disease, or PTCLD), as well as in individuals with no history of B. burgdorferi infection.

Contrary to the name, however, and despite extensive study, no clear evidence has emerged to support the contention that CLD results from a past or persistent Lyme disease infection. For that reason, the majority of physicians and scientists do not support a diagnosis of CLD, and a recent medical appraisal of CLD concluded that the term is a misnomer (New Eng. J. Med. 2008; 357:1422-30).

How is Lyme disease treated?

For early Lyme disease, a short course of oral antibiotics such as doxycycline or amoxicillin is curative. In rarer, more complicated cases, laboratory-diagnosed Lyme disease can usually be successfully treated with 3 to 4 weeks of antibiotic therapy.

Because the symptoms sometimes associated with CLD have not been linked to a current Lyme disease infection, the majority of scientists and physicians believe that continued antibiotic therapy for the disease is both unwarranted and potentially dangerous in treating patients with those symptoms in the absence of a confirmed bacterial infection.

Has NIAID looked at the potential benefits of long-term antibiotic therapy on CLD?

Yes. In an effort to address the confusion regarding appropriate therapy, NIAID has funded three placebo-controlled clinical trials on the efficacy of prolonged antibiotic therapy for the treatment of CLD/PTCLD. The published results were subjected to rigorous statistical and scientific peer review.

These trials were designed to ensure that several key parameters were addressed:

• The susceptibility of Borrelia burgdorferi, the causative agent of Lyme disease, to the antibiotics used
• The ability of the antibiotics used to both cross the blood-brain barrier and access the central nervous system and to persist at effective levels throughout the course of therapy
• The ability of the antibiotics used to kill bacteria living both ouside and inside mammalian cells
• The safety and welfare of patients enrolled in the trials

Two multicenter studies provided no evidence that extended antibiotic treatment is beneficial (New Eng. J. Med. 345:85-92, 2001). In those studies, physicians examined long-term antibiotic therapy in patients with a well-documented history of previous Lyme disease, but who reported persistent pain, fatigue, impaired cognitive function, or unexplained numbness. Those symptoms are common among individuals reporting CLD. Patients were treated with 30 days of an intravenous antibiotic followed by 60 days of an oral antibiotic.

The study reinforced the evidence that patients reporting PTCLD symptoms can have a very real, severe impairment in overall physical health and quality of life. However, results showed no benefit from prolonged antibiotic therapy when compared with placebo in treating those symptoms.

In another study, researchers examined the effect of 28 days of intravenous antibiotic compared with placebo in 55 patients reporting persistent, severe fatigue at least 6 months following treatment for laboratory-diagnosed Lyme disease. Patients were assessed for improvements in self-reported fatigue and cognitive function. (Neurology 60:1923-30, 2003).

In that study, individuals receiving antibiotics did report a greater improvement in fatigue than those on placebo. However, individuals receiving antibiotics were more likely to correctly guess which study group they were in, and, therefore, the potential for a placebo-like effect cannot be eliminated. No benefit to cognitive function was observed. In addition, six of the study individuals had serious adverse events associated with intravenous antibiotic use, four requiring hospitalization. Overall, the study authors therefore concluded that additional antibiotic therapy for PTCLD was not supported by the evidence.

If long-term antibiotic therapy is not effective against CLD, why do some individuals report improved symptoms following such treatment?

Carefully designed, placebo-controlled studies have failed to demonstrate that prolonged antibiotic therapy is beneficial. Although isolated success stories are always good to hear, such reports alone are not sufficient grounds to support a therapeutic approach.

A positive response to prolonged antibiotic therapy may be due to the placebo effect, which was reported as high as 40 percent in the studies described above. Other investigators also have noted periodic improvements in the symptoms of patients given only placebo during the course of their studies.

Another explanation could be related to unanticipated beneficial effects of antibiotics, unrelated to their antimicrobial properties. Many antibiotics have well-established anti-inflammatory properties. Some, including several of those used in prolonged treatment regimens for CLD, also have profound neuroprotective properties that might help relieve neurological symptoms (Trends Pharmacol. Sci. 25: 609, 2004; Nature 433: 73, 2005; Neurobiol. 25: 514, 2007).

It is conceivable that such pharmacologic effects, rather than the elimination of a presumed but undocumented persisting infection, could account for some of the beneficial effects noted in some CLD patients receiving antibiotic therapy. If true, those patients may be better served with specific anti-inflammatory and/or neuroprotective drugs.

In the absence of evidence for a persisting infection, some have suggested treatment with gabapentin or pregabalin (Lyrica®) to alleviate symptoms associated with CLD. In one relatively small clinical trial, gabapentin was effective in reducing nerve pain in individuals with neuroborreliosis, an occasional late manifestation of Lyme disease (Dermatology 211:123, 2005). That approach to therapy warrants additional study. It also should be noted that the FDA has recently approved the use of pregabalin (Lyrica®) for the treatment of fibromyalgia, a condition with symptoms very similar to those ascribed to CLD.

I thought antibiotics were safe. If so, what is the harm in prescribing them?

Overall, antibiotics are a very safe group of drugs, but uncontrolled use can lead to problems. Because few antibiotics are highly specific, they not only destroy “bad” bacteria but also kill many of the beneficial bacteria that inhabit the body. These good bacteria play a critical role in maintaining general health and preventing disease-causing organisms from establishing a foothold. Serious, potentially fatal antibiotic-associated infections remain a major concern in hospitals, and thus antibiotic use is monitored carefully. Intravenous antibiotics, such as those sometimes promoted for treating symptoms attributed to CLD, require lines and catheters that present an avenue for dangerous secondary infections to take hold.

Patients also risk negative and sometimes serious reactions to the antibiotics themselves. In the first studies described above, 25 percent of the patients in the treatment group experienced study-related adverse events (New Engl. J. Med. 345:85-92; 2001). In the clinical trial looking at cognitive function, six patients experienced serious adverse events, four of whom required hospitalization.

In addition to personal safety concerns, unnecessary antibiotic use contributes to the serious, growing problem of antimicrobial resistance. Overuse of antibiotics has led to many bacteria developing resistance to the very drugs doctors once used to combat them.

If CLD is not caused by a persistent B. burgdorferi infection, could it still be related to Lyme disease in some way?

According to studies conducted and/or funded by NIAID and the National Institute of Neurological Disorders and Stroke, some cases of CLD may result from autoimmune disease perhaps triggered by an initial B. burgdorferi infection. Research in this area is ongoing.

More information on these and other studies can be found on the NIAID Lyme disease Web site.

Where can I find additional information on NIAID’s efforts to better understand Lyme disease?

The Centers for Disease Control and Prevention also maintains a Web site on Lyme disease.

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