This article is more than 5 years old. Information may no longer be current.
Controversies surround treatment of Lyme disease
IDSA and ILADS disagree on the optimal therapy for patients with Lyme disease.
Click Here to Manage Email Alerts
TORONTO – The duration of treatment for Lyme disease has become a somewhat divisive issue among physicians. Fueling this controversy, two major medical associations – the Infectious Disease Society of America and the International Lyme and Associated Diseases Society – have released diverging recommendations regarding the diagnosis and treatment of Lyme disease.
At the Infectious Disease Society of America’s (IDSA) 44th annual meeting, Raphael Stricker, MD, president of the International Lyme and Associated Diseases Society (ILADS) and medical director of Union Square Medical Associates in San Francisco, and Paul Auwaerter, MD, clinical director of the division of infectious diseases at Johns Hopkins University School of Medicine in Baltimore, discussed the controversy regarding treatment for Lyme disease.
Difficult to diagnose
Stricker said he believes one factor adding to the Lyme disease controversy is that the disease can be difficult to diagnose. The classical symptoms of Lyme disease, transmitted by tick bite, include a bullseye–shaped rash and swelling or pain in the joints.
“The problem is that these classic features of Lyme disease are somewhat unreliable,” Stricker said. “Only 50% to 60% of patients typically recall a tick bite; the rash is reported in only 35% to 60% of patients; joint swelling typically occurs in only 20% to 30% of patients.” Stricker added that in some patients, joint swelling may be masked by anti-inflammatory medication.
Stricker said many patients with Lyme disease will continue to experience a variety of symptoms, even after treatment. “Some of these patients may go on to develop a syndrome of multiple, nonspecific symptoms, making it very difficult to diagnose and treat as Lyme disease,” he said. “The question becomes: is this post-Lyme syndrome or a persistent infection?”
One reason for the difficulties in diagnosing Lyme disease is that Borrelia burgdorferi, the spirochete that is the disease’s causative agent, has an unusual genetic makeup. This spirochete contains more than 1,500 gene sequences and has at least 132 functioning genes. Due to the organism’s complex pathophysiology, it can evade the body’s immune system, thus making it more difficult to eradicate.
According to Stricker, Borrelia burgdorferi invades multiple tissues and is able to assume a dormant state much like tuberculosis, which can add to the diagnostic difficulties.
In addition to these complicating factors, laboratory testing for Lyme disease is flawed. “Lab testing is not very good for the diagnosis of Lyme disease,” Stricker said. “Commercial testing has about a 90% specificity but only a 50% to 60% sensitivity. This is too insensitive for a reliable diagnostic test.”
Extended therapy
In accordance with the position of ILADS, Stricker said he believes extended therapy for Lyme disease is sometimes necessary, particularly in later disease that is more difficult to eradicate.
Stricker also noted that failure to respond to current Lyme disease treatments may be more common than many doctors realize. “Culture-confirmed failure of antibiotic treatment was first reported in 1989,” he said. “Studies have shown that Borrelia burgdorferi can persist after antibiotic treatment.”
This remains a particularly contentious issue and many in the medical community believe there is insufficient evidence to prove the persistence of Borrelia burgdorferi after antibiotic treatment. But Stricker noted that several studies conducted in animals – including mice, dogs and monkeys – indicate that the bacteria can persist after treatment is completed. Persistence in humans has been confirmed by culture or molecular testing in at least 12 studies.
Stricker added that there is extensive clinical evidence supporting a longer duration of antibiotic therapy in treating chronic Lyme disease. Studies from several teams of researchers indicated that a longer duration of treatment may be beneficial for some patents with Lyme disease. “Prolonged antibiotic therapy appears to be useful and appropriate in persistent Lyme disease,” Stricker said.
Science in this area is still evolving, according to Stricker. “We don’t have all the answers and it is too early to adopt treatment strategies that assume we do. Meanwhile, doctors need flexible treatment approaches,” he said.
Tickborne coinfections may also be a problem and may exacerbate the symptoms of Lyme disease. “If a patient comes back in follow-up and has symptoms that have persisted or symptoms that have gotten worse, it may be because they are coinfected,” Stricker said. “Although these patients have been treated for Borrelia burgdorferi, they may have coinfection with babesia, anaplasma, ehrlichia or bartonella.” He added that extended antibiotic therapy may help to treat these coinfections as well.
IDSA’s view
Concurring with the IDSA, Auwaerter said he disagrees that extended therapy is the best option for patients with Lyme disease. “Long-term antibiotics are not in your patients’ best interest,” he said. “Prospective data do not suggest a significant benefit from longer term courses of antibiotics in patients with Lyme disease.”
Auwaerter urged health care professionals to consult the new IDSA guidelines for treatment of Lyme disease, which were released in October.
In addition to offering recommendations for treatment of Lyme disease, the new guidelines attempt to clarify the disease. Auwaerter said the controversy regarding Lyme disease treatment may be related to the lack of definitive data and confusing terminology. For example, he said chronic Lyme disease should be called “Post Lyme Disease Syndrome.” The definition of this is one of the most important additions to the new guidelines. Patients should be considered to have this syndrome if they still have symptoms of Lyme disease after six months, defined by the CDC criteria; patients who had these symptoms prior to the diagnosis of Lyme disease should be excluded. Post Lyme Disease Syndrome may be present if patients are still experiencing symptoms such as fatigue, widespread musculoskeletal pain, cognitive problems and a significant reduction in functional status after an appropriate antibiotic course.
“The subjective problems may be difficult to quantify, but the patient does not feel well and it is a marked difference from the past,” Auwaerter said. However, he stated that even if patients have Post Lyme Disease Syndrome, longer-term therapy with antibiotics may not offer a significant benefit.
A lack of evidence
Auwaerter said there is a lack of evidence to indicate that long-term antibiotic therapy will help to cure Lyme disease. “Longer term therapy with antibiotics does not influence outcomes,” he said.
He noted one study by Klempner et al that examined 78 patients with Lyme disease; the average duration of symptoms of Lyme disease was four years. The patients were randomized to treatment with either an antibiotic regimen or placebo. All patients had well-documented Lyme disease and had already been treated with an initial therapy of antibiotics at baseline. After antibiotic therapy of up to 180 days, the results were similar in both treatment groups. In both the placebo group and the antibiotic group, one-third of patients improved, one-third stayed the same and one-third worsened; there was no statistical difference in outcomes between groups.
A companion study examining cognitive functioning in 129 patients with Lyme disease indicated that although 70% of patients said they had impaired neurocognitive functioning, tests showed no reduction in neurocognitive functioning. “The interesting part was that the neurocognitive testing was normal in all patients,” Auwaerter said. “Although patients reported neurocognitive problems, they performed well on tests.”
Auwaerter noted another study by Krupp et al that showed there was some reduction in fatigue in patients with Lyme disease after six months of antibiotic therapy. “But this is only one subjective parameter and there was no change in any other primary endpoint,” he said.
Auwaerter said he agrees with the new IDSA guidelines and urges doctors to avoid extended antibiotic therapy for patients with Lyme disease. “We should treat patients on the basis of what we know, not on the basis of theory,” he said. “Furthermore, for many patients, long term antibiotic therapy can have complications.” – by Jay Lewis
The new IDSA Lyme Disease Guidelines have indeed proven to be contentious. Those of you who have followed the IDSA News Clips since their release have been treated to a series of newspaper articles, mostly from areas of Lyme disease endemicity, and seemingly initiated by unhappy patients. Phraseology applied to the Guidelines include words such as “object strenuously,” “with great alarm,” “reckless,” “a travesty,” “outrageous,” and on and on. Obviously, many patients who are desperate to believe they have Lyme Disease are unhappy because their beliefs have not been validated in the Guidelines. Insurance reimbursement issues are playing a major role as well. The Connecticut Attorney General’s office is investigating the IDSA Guideline Development process, and a bill is likely to be introduced into the Massachusetts Legislature in the next term to prohibit the state medical board from disciplining physicians who prescribe long-term antibiotics to patients with alleged chronic Lyme disease. So stay tuned, there’s more to come.
– Theodore C. Eickhoff, MD
Chief Medical Editor
For more information:
- Stricker R, Auwaerter P. Controversies in Lyme disease diagnosis and treatment. Presented at: The 44th annual meeting of the Infectious Disease Society of America; Oct. 12-15, 2006; Toronto.